One mechanism of sudden sensorineural hearing loss after sildenafil and sexual activity.

OBJECTIVES: A case of sudden sensorineural hearing loss following use of sildenafil was examined in detail over a period of three days from first report to recovery. DESIGN: Case study. The subject presented with sudden sensorineural hearing loss and diplacusis a day after onset. Testing involved detailed interview, standard audiometry, detailed inter-octave audiometry, and measurement of detailed psychophysical frequency tuning curves during a two day recovery period. STUDY SAMPLE: One male aged in his thirties with otherwise normal hearing. RESULTS: Although standard audiometry was within normal limits, detailed inter-octave audiometry and psychophysical frequency tuning curves were consistent with a punctate unilateral intra-cochlear lesion that resolved over a period of three days. CONCLUSIONS: This is the first report of such a frequency-specific audiometric shift and diplacusis after sildenafil, and is not consistent with previous reports of direct ototoxic pharmacological effects. We propose that the lesion was most likely caused by a cochlear bleed, and may have been due to physical exertion rather than a direct pharmaceutical effect. The study highlights the important role of additional diagnostic testing that can be easily achieved in a clinical setting with minimal equipment.

A meta-analysis comparing the performance of narrowband CE-Chirp and 500 Hz tone burst stimuli in recording cervical vestibular evoked myogenic potential (cVEMP).

Due to contradictory outcomes in the literature, the aim of this meta-analysis is to verify whether the narrowband (NB) CE-Chirp stimulus (centred at 500 Hz) would produce more robust cervical vestibular evoked myogenic potential (cVEMP) responses relative to the conventional 500 Hz tone burst. The literature search was conducted using PubMed, Scopus, and Web of Science databases and the terms used were "vestibular evoked myogenic potential" and "chirp". The cVEMP parameters to be analysed were P1 latency, N1 latency, and P1-N1 amplitude. A total of 59 potential articles were obtained from the database search. Eventually, five articles were found to be eligible for the meta-analysis (with n = 222). As found, P1 and N1 latencies of cVEMP were significantly shorter for the chirp stimulus (p < 0.001), with substantially large effect sizes. On the other hand, P1-N1 amplitude values were found to be not statistically different between the two stimuli (p = 0.189), with a small effect size. It appears that there is no indication to support the superiority of the NB CE-Chirp stimulus (centred at 500 Hz) in the cVEMP testing (relative to the conventional 500 Hz tone burst). In particular, both stimuli produce comparable P1-N1 amplitude values. Even though P1 and N1 latencies are statistically shorter for the chirp stimulus, this may not reflect that it should be the preferred stimulus for recording cVEMP responses (and the reasons for this are discussed accordingly).

The Narrowband CE-Chirp Stimulus Does Not Necessarily Produce More Robust Cervical Vestibular Evoked Myogenic Potential.

OBJECTIVE: Various studies have been conducted to search for the most optimal stimulus for eliciting cervical vestibular evoked myogenic potential (cVEMP). More recently, there is a growing interest to study the usefulness of chirp stimuli in cVEMP recording. Nevertheless, contradictory outcomes have been reported across the studies, and further research with larger samples would be beneficial to provide better insight into this matter. As such, the present study was carried out to compare cVEMP results between narrowband (NB) CE-Chirp (centered at 500 Hz) and 500 Hz tone burst stimuli. DESIGN: In this study that employed a comparative study design, 98 normally hearing adults aged between 19 and 24 years were enrolled. All of them underwent the cVEMP testing based on the recommended test protocol. The stimuli were a 500 Hz tone burst and a NB CE-Chirp (360-720 Hz) presented through insert earphones at an intensity level of 120.5 dB peSPL. RESULTS: For each stimulus, cVEMP results did not differ significantly between the ears ( p > 0.05). Relative to the 500 Hz tone burst, the NB CE-Chirp stimulus produced statistically shorter P1 and N1 latencies ( p < 0.001). On the other hand, P1-N1 amplitude was found to be comparable between the two stimuli ( p > 0.05). CONCLUSIONS: The present study did not find any supporting evidence that the NB CE-Chirp stimulus (centered at 500 Hz) outperformed the conventional 500 Hz tone burst in the cVEMP testing. Both stimuli are considered equally appropriate to record cVEMP responses in clinical settings.

Acoustic impedance rhinometry (AIR): a technique for monitoring dynamic changes in nasal congestion.

We describe a simple and inexpensive method for monitoring nasal air flow resistance using measurement of the small-signal acoustic input impedance of the nasal passage, similar to the audiological measurement of ear drum compliance with acoustic tympanometry. The method requires generation of a fixed sinusoidal volume-velocity stimulus using ear-bud speakers, and an electret microphone to monitor the resultant pressure fluctuation in the nasal passage. Both are coupled to the nose via high impedance silastic tubing and a small plastic nose insert. The acoustic impedance is monitored in real-time using a laptop soundcard and custom-written software developed in LabView 7.0 (National Instruments). The compact, lightweight equipment and fast time resolution lends the technique to research into the small and rapid reflexive changes in nasal resistance caused by environmental and local neurological influences. The acoustic impedance rhinometry technique has the potential to be developed for use in a clinical setting, where the need exists for a simple and inexpensive objective nasal resistance measurement technique.

Rotation of the eyes (not the head) potentiates the postauricular muscle response.

OBJECTIVE: The authors investigated how eye and head rotation modulate the human postauricular muscle response (PAMR), to determine the optimal strategy for potentiating the PAMR, or minimizing it to reduce contamination of small neurogenic responses. DESIGN: The authors recorded the PAMR evoked by binaural bipolar clicks (50 dB SL, 360 µsec per phase with 53-msec interval) from behind the right ear of 12 normally hearing adults, and attempted to enhance it with (a) voluntary ear contraction alone, (b) head rotation alone (with the eyes forward-directed and tracking a target attached to the head), or (c) by lateral eye movement alone (toward the right measurement side, with the head facing forward). RESULTS: When the head alone was rotated with eyes fixed relative to the head, the PAMR increased only slightly in some subjects, as did the ongoing electromyography (EMG) (probably due to EMG activity from nearby neck muscles). On returning the head to the forward control position, the PAMR dropped rapidly to control amplitudes. When the eyes alone were rotated, both the EMG and the PAMR increased markedly in most subjects, and returning the eyes to their control position produced a gradual return to control amplitudes. Voluntary PAM contraction (in those subjects who could accomplish it) increased the EMG tone and the PAMR amplitude concomitantly, with vigorous voluntary PAM contraction saturating the PAMR but not the EMG. CONCLUSION: Head rotation alone was not effective in potentiating the PAMR when lateral eye movement relative to the head was avoided during the head rotation maneuver. When lateral eye movement was controlled appropriately, the PAMR could be potentiated reliably, or reliably avoided when recording smaller neurogenic responses. If head rotation was used to optimize the PAMR without explicit control of eye movement, a false impression of variability was produced.

Ion flow in cochlear hair cells and the regulation of hearing sensitivity.

This paper discusses how ion transport proteins in the hair cells of the mammalian cochlea work to produce a sensitive but stable hearing organ. The transport proteins in the inner and outer hair cells are summarized (including their current voltage characteristics), and the roles of these proteins in determining intracellular Ca(2+), membrane potential, and ultimately cochlear sensitivity are discussed. The paper also discusses the role of the Ca(2+) sequestration sacs in outer hair cells in the autoregulation of hair cell membrane potential and cochlear gain, and how the underdamped control of Ca(2+) within these sacs may produce the observed slow oscillations in cochlear sensitivity and otoacoustic emissions after cochlear perturbations, including perilymphatic perfusions and prolonged low-frequency tones. The relative insensitivity of cochlear gain to short-term changes in the endocochlear potential is also discussed.

Ion flow in stria vascularis and the production and regulation of cochlear endolymph and the endolymphatic potential.

This paper reviews some of what is known about ion transport through the cells of the mammalian stria vascularis, and discusses how the endolymph and endocochlear potential in scala media are produced by the stria's main cell types. It discusses the role of each cells' ion transport proteins from an engineering perspective, and the advantages and disadvantages in using the different transport proteins in the different cells to perform their different roles. To aid this discussion, the use of spreadsheet analysis in the modelling of ion transport in single cells and homogenous epithelia is outlined, including the current-voltage (IV) characteristics of the three main categories of transport proteins (pores, ports and pumps), and the constraint equations that apply under various conditions (the voltage or ionic steady states in the open- and closed-circuit conditions). Also discussed are the circulation of K(+) within the cochlea, and the chloride, salt and water balance of scala media and stria vascularis, and what transport processes may be required to maintain such a balance.

Evidence that the compound action potential (CAP) from the auditory nerve is a stationary potential generated across dura mater.

We have investigated the generation of the compound action potential (CAP) from the auditory nerve of guinea pigs. Responses to acoustic tone-bursts were recorded from the round window (RW), throughout the cochlear fluids, from the surface of the cochlear nucleus, from the central end of the auditory nerve after removal of the cochlear nucleus, from the scalp vertex, and from the contralateral ear. Responses were compared before, during and after experimental manipulations including pharmacological blockade of the auditory nerve, section of the auditory nerve, section of the efferent nerves, removal of the cochlear nucleus, and focal cooling of the cochlear nerve and/or cochlear nucleus. Regardless of the waveform changes occurring with these manipulations, the responses were similar in waveform but inverted polarity across the internal auditory meatus. The CAP waveforms were very similar before and after removal of the cochlear nucleus, apart from transient changes that could last many minutes. This suggests that the main CAP components are generated entirely by the eighth nerve. Based on previous studies and a clear understanding of the generation of extracellular potentials, we suggest that the early components in the responses recorded from the round window, from the cochlear fluids, from the surface of the cochlear nucleus, or from the scalp are a far-field or stationary potential, generated when the circulating action currents associated with each auditory neurone encounters a high extracellular resistance as it passes through the dura mater.

Frequency-specific electrocochleography indicates that presynaptic and postsynaptic mechanisms of auditory neuropathy exist.

OBJECTIVES: The physiological mechanisms underlying auditory neuropathy (AN) remain unclear and it is likely that the multiple disruptions are classified under the broadly defined term. Cochlear implantation is being more widely used in this population to bypass the suspected site-of-lesion although a number of cases have been identified within the Sydney Cochlear Implant Centre where this management strategy has been unsuccessful. It is likely that this relates to the different physiological mechanisms underlying AN. DESIGN: To investigate the site-of-lesion in AN, frequency-specific round window electrocochleography (ECochG) was used to assess local hair-cell, dendritic, and axonal currents generated within the cochlea in 14 subjects with AN and compared with responses from two normally hearing subjects. ECochG results were then compared with electrically evoked auditory brain stem response (EABR) measured after cochlear implantation. RESULTS: The results of this study demonstrate that two dominant patterns of ECochG waveforms (produced by a high-frequency alternating tone burst) can be identified in this population of AN subjects: (a) gross waveform showing a prolonged summating potential (SP) latency that, in most cases, is followed by a small compound action potential; and (b) gross waveform showing a normal latency SP waveform followed by a broad negative potential [assumed to reflect the dendritic potential (DP) identified in anaesthetized guinea-pigs]. This study demonstrates that in most subjects (n = 7) with a prolonged latency SP but no DP, normal morphology EABR waveforms were elicited for all electrode channels. On the other hand, all subjects (n = 7) who showed a normal latency SP followed by a broad negative DP, showed EABR waveforms that were absent or having poor wave V morphology. The authors' interpretation of this is that ECochG results may provide a classification of AN into pre- and postsynaptic lesions. CONCLUSIONS: We suggest that a presynaptic and postsynaptic type of AN exist that may have implications for the fitting of cochlear implants.

Changes in cochlear responses in guinea pig with changes in perilymphatic K+. Part I: summating potentials, compound action potentials and DPOAEs.

We have measured the effects of changing perilymphatic K+ by perfusing scala tympani in guinea pigs with salt solutions high or low in K+, while monitoring the distortion product otoacoustic emissions (DPOAEs) in the ear canal (a measure of mechanical vibration of the organ of Corti), the summating potential (SP) evoked by high-frequency tone-bursts (taken to be a measure of pre-synaptic electrical activity of the inner hair cells) and the compound action potential (CAP) of the auditory nerve (taken to be a measure of post-synaptic neural activity). We have attempted to investigate the osmotic effects of our perfusates by comparison with simple hyperosmotic sucrose perfusates and iso-osmotic versions of perfusates, and for the effects of changes in other ions (e.g. Na+ and Cl-) by keeping these constant in some perfusates while elevating K+. We have found that changing the K+ concentration over the range 0-30mM elevated the SP and CAP thresholds almost equally in normal animals, and not at all in animals devoid of outer hair cells (OHCs), showing that OHCs are sensitive to the perfusates we have used, but the inner hair cells (IHCs) and the type I afferent dendrites are not, presumably because IHCs are shielded from perilymph by supporting cells, and the membranes of the afferent dendrite membranes exposed directly to our perfusates are dominated by Cl(-) permeability, rather than by K+ permeability. This view is supported by experiments in which the perilymphatic Cl(-) concentration was reduced, producing a large elevation in CAP threshold, but a much smaller elevation of SP threshold, suggesting disruption of action potential initiation. The view that threshold elevations with changes in perilymphatic K+ are due almost solely to a disruption of OHC function and a consequent change in the mechanical sensitivity of the organ of Corti was supported by measurements of amplitude of the 2f1-f2 distortion product otoacoustic emission. During elevations in K+, DPOAEs followed a similar time-course to that for SP and CAP, although the changes were less for DPOAEs. The lack of a 1:1 relationship between DPOAEs and SP and CAP is probably because the iso-input DPOAE measure used is a more complex indicator of mechanical sensitivity than the iso-output measure used by others. Taken together, these results suggest that changes in K+ in pathological conditions probably produce a hearing loss by disrupting OHCs rather than IHCs or neurones, and that OHC disruption in our experiments was due to a mixture of osmotic, K+ and possibly Cl(-) effects.

Mathematical model of outer hair cell regulation including ion transport and cell motility.

To understand the regulatory processes within the cochlea, and outer hair cells (OHCs) in particular, we have developed a mathematical model of OHC regulation that takes into account their known electrical properties, and includes fast and slow somatic motility. We model how cytosolic Ca(2+) is involved in regulation of (i) the OHC membrane potential, (ii) the operating point of OHC mechano-electrical transduction (MET) channels via slow motility; (iii) basolateral wall K(+) permeability via Ca(2+)-sensitive K(+) channels; and (iv) cytosolic concentrations of Ca(2+) itself, via Ca(2+)-ATPase-mediated sequestration within the OHCs and Ca(2+)-induced Ca(2+)-release (CICR) from the same intracellular Ca(2+) storage organelles. To account for some aspects of the cochlea's transient response to experimental perturbations, we have included a putative intracellular second-messenger cascade based on cytosolic Ca(2+). Overall, the OHC basolateral permeability determines the resting membrane potential of the OHCs and their standing current, which influences the endocochlear potential, and also affects the AC receptor potential that drives the prestin-mediated somatic electromotility and active cochlear gain. The model we have developed provides a physiologically-plausible and internally-consistent explanation for the time-courses of the cochlear changes we have observed during a number of different experimental perturbations, including a slow oscillatory behaviour presumed due to oscillations in cytosolic Ca(2+) concentration. We also show how the known ionic mechanisms within OHCs act to regulate membrane potential and hair bundle angle over a very wide range of strial current and intracochlear hydrostatic pressure. Not included in the model are osmotic effects, the nonlinear aspects of prestin's electromotility, the intracellular role of Cl(-) in modifying this motility, nor adaptation of MET at the apex of OHCs. Only one Ca(2+) sequestration compartment has been included in this implementation of the model, with the two types of basolateral Ca(2+) cisternae combined into a single compartment. Despite these limitations, the model as presented offers insights into the regulation of OHC membrane potential and MET at the hair cell apex, and is our first step in understanding in a quantitative way the integrated function of the molecular components of ion transport and motility in these cells.

The post-auricular muscle response: an objective electrophysiological method for evaluating hearing sensitivity.

Post-auricular muscle responses (PAMRs) were recorded in sixteen adults with normal hearing and twenty adults with sensorineural hearing loss. Click stimuli were presented at 20 to 80 dB nHL via insert earphones. Only one ear was tested in hearing-impaired subjects, but normal-hearing subjects were tested monaurally and binaurally. PAMR amplitudes declined and latencies increased with decreasing click intensity. Both binaural stimulation and eye turn enhanced the PAMR. In hearing-impaired subjects, PAMR thresholds were correlated with audiometric thresholds for the eyes-turned condition. All normal-hearing subjects had PAMR when recording conditions were optimized and half had responses for the least optimal condition (20 dB nHL, monaural, eyes front). With eyes turned and monaural clicks at 35 dB nHL, the level widely used for infant hearing screening, most normal-hearing adults had a PAMR. Thus the PAMR is a robust response that may be a useful adjunct to ABR for objective hearing assessment.

Rising-frequency chirps and earphones with an extended high-frequency response enhance the post-auricular muscle response.

The purpose of this study was to determine whether rising-frequency chirps presented via earphones with an extended high-frequency response would optimize the post-auricular muscle response (PAMR). The PAMR was recorded in adults using three different stimuli (a click, a rising-frequency chirp, and a truncated speech stimulus, /t/). Conventional ER-3A insert earphones were compared to ER-2 insert earphones to determine whether the PAMR is enhanced by the ER-2's extended highfrequency response. There were significant stimulus and earphone effects on PAMR amplitudes. The PAMR was largest for the chirp stimulus and the ER-2 earphones. The poorest responses were obtained using the /t/ stimulus and conventional ER-3A earphones. The results support previous ABR studies that have demonstrated a significant advantage of chirps over clicks for evoked response audiometry, and indicate that the PAMR is enhanced by inclusion of additional high-frequency stimulus energy.

Primary afferent and cochlear nucleus contributions to extracellular potentials during tone-bursts.

Gross electrical responses to tone bursts were measured in the guinea pig with electrodes located in scala tympani (ST) and scala vestibuli (SV) of the cochlea, on the central portion of the VIIIth nerve fibres in the internal auditory meatus, and on the surface of the cochlear nuclear complex (CN). Intracochlear perfusion of pharmacological blockers of neural and postsynaptic activity as well as aspiration of parts or all of the CN were used to dissect the origin of the many components of the gross responses. It was shown that single-ended recordings from either ST or SV or those derived from the sum of the ST and SV responses not only contain mixed responses from the auditory nerve fibres and cochlear hair cells, but are contaminated or modified by neural activity central to the internal auditory meatus, probably in various parts of the CN. Differential recordings between ST and SV were relatively uncontaminated by such activity. Recordings from central locations were largely uncontaminated by potentials from cochlear hair cells. These results suggest that a revised and extended system of nomenclature for the different components of the gross cochlear potentials is necessary, and interpretation of such potentials needs to take into account multiple central as well as peripheral generators.

The origin of the 900 Hz spectral peak in spontaneous and sound-evoked round-window electrical activity.

We have monitored the spectrum of the (spontaneous) neural noise at the round window (RW) and on the surface of the antero-ventral cochlear nucleus (CN) and the dorsal CN (DCN) of anaesthetised guinea pigs. We have also obtained the average gross extracellular waveform evoked by 20 kHz tone-bursts (0.25 ms and 25 ms) at each of these recording sites, and calculated the spectrum of the average waveforms (SAW). With these tone-bursts, only a small population of neurones in the extreme basal turn of the cochlea near the RW electrode responds, presumably with only a single action potential for each 0.25 ms tone-burst. The RW waveforms recorded between 20 dB and 60 dB SPL were very similar, and are therefore presumably a simple estimate of the shape of the contribution of the firing of a single neurone to the gross RW signal (the unitary potential or UP). In normal animals, the SNN and the SAW were remarkably similar, with peaks at 900 Hz and at 2400 Hz, suggesting that they are not due to neural synchronisation (as suggested previously by others), but are due to an oscillatory waveform produced by each single fibre action potential. Abolition of all spike activity by RW tetrodotoxin left a waveform with only a summating potential and a dendritic potential, and no 900 Hz peak in the SAW or SNN, indicating that the spectral peak is due to neural spiking only. Abolition of the CN contribution to the RW waveforms by CN application of lignocaine or sectioning of the cochlear nerve at the internal meatus (by focal aspiration of the DCN and underlying cochlear nerve) showed that the 900 Hz peak was not simply due to the addition of a delayed and inverted CN contribution: mathematical modelling shows that this would produce a broad spectral peak at about 1200 Hz. Moreover, the 900 Hz spectral peak remains after complete abolition of the CN contribution, although reduced in amplitude. This residual 900 Hz peak can be traced to an oscillation in the gross waveform due to the presence of two peaks (P(1)* and N(2)*) which follow the intact N(1) peak. The P(1)* and N(2)* peaks were present at the RW, but not at the cochlear nerve as it exits the internal meatus, suggesting that they were not due to double-spiking of some of the neurones, but were probably due to a sub-threshold electrical resonance in the peripheral dendrites. We have successfully modelled the production of the SNN and the compound action potential and SAW in response to 0.25 ms and 25 ms tone-bursts at 20 kHz by including only a damped 900 Hz resonance in the UP, without refractory effects, preferred intervals or synchronisation in the timing of neural spike generation. Such resonances in other neurones are known to be due to the activation kinetics of the voltage-controlled sodium (Na(+)) channels of these neurones. The presence of such sub-threshold oscillations probably indicates that the peripheral dendrites are devoid of stabilising potassium (K(+)) channels. We also discuss the role of this membrane resonance in generating burst-firing of the cochlear nerve (as with salicylate) and the role of such burst-firing in generating tinnitus.

Non-linear aspects of outer hair cell transduction and the temporary threshold shifts after acoustic trauma.

The 200-Hz cochlear microphonic potential (CM) and the compound action potential (CAP) of the auditory nerve evoked by tone-bursts were recorded in the basal turn of the cochlea of anaesthetised guinea pigs, before and after exposure to traumatic high-frequency tones that produce a temporary threshold shift (TTS) in this cochlear region. The drop in CM and the TTS were highly correlated, suggesting that it is the disruption of the outer hair cells generating the CM that causes the TTS. The previously measured rise in endocochlear potential and drop in organ of Corti K+ levels suggest that the TTS is due to a temporary closure of outer hair cell mechanoelectrical transduction (MET) channels, which produces a drop in the mechanical sensitivity of the organ of Corti, due to disruption of the active process provided by outer hair cells. The time course of the onset and recovery of TTS is consistent with a kinetic folding and refolding of MET channels over a time course of hours and days. Mathematical modelling of this putative channel folding suggests that TTS recovery may be accelerated by the presentation of additional sounds during the recovery period. We present electrophysiological data (CM and CAP measurements) showing that this accelerated recovery occurs. Using two-tone complexes (phase-locked 5- and 10-kHz traumatic tones, and 10-kHz traumatic tones with 25-Hz bias tones), we also show that the mechanisms producing TTS are non-linear and asymmetric, and that the greatest 'trauma' occurs when the hair bundles of outer hair cells are deflected away from the basal body of these cells (i.e. in the direction normally causing hyperpolarisation of the cell membrane potential).