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A L Nuttall

Publications and source records attributed to A L Nuttall.

At least 19 recordsLinked to original sources
PubMed2000

Quantitative measure of multicomponents of otoacoustic emissions.

A method for quantitatively measuring measuring multicomponents of otoacoustic emissions (OAE) was developed in this study. The method is based on the rationale that, if the acoustic emission is a vector sum of multicomponents coming from different locations in the cochlea, each component will show a delay. The proposed method consists of the following steps: (1) the amplitude and phase of the emission is measured when the emission frequency is swept; (2) the real part of the spectrum is obtained based on the amplitude and phase spectra; and (3) the real part of the emission spectrum is then analyzed using a Fourier transform to extract the multiple components. The theoretical basis and practical procedure of this method are described, and in vitro and in vivo tests are used to demonstrate the validity of the method. Preliminary data demonstrate the multicomponents of the extracochlear electrically evoked otoacoustic emission (EEOAE).

Acoustic Stimulation↗
PubMed2000

Fine structure and multicomponents of the electrically evoked otoacoustic emission in gerbil.

Like the acoustically evoked distortion product otoacoustic emissions (DPOAE), the amplitude spectrum of the extracochlear electrically evoked otoacoustic emission (EEOAE) also shows peaks and valleys, which are termed the fine structure (FS) of the EEOAE. The hypothesis that the FS of the EEOAE is generated by multiple wave interactions in the cochlea is investigated by examining the relationship between the FS and the multiple-delay components of the EEOAE. The bulla of the gerbil was exposed using a ventral surgical approach. One pole of a bipolar electrode was placed in the round window niche, and the other pole on the surface of the first cochlear turn. A microphone was used to measure electrically evoked sound pressure change in the ear canal. A recently developed multicomponent analysis method was used to detect the EEOAE multiple delays. It was found that the FS is the spectral representation of the multiple-delay components. The relative power of a prominent long delay component (LDC) shows a negative relationship to the electrical stimulus level. Both the FS and the LDC were abolished by intravenous furosemide. Reconstructed signals showed that mathematical removal of the EEOAE LDC also completely eliminated the FS. These data demonstrate that the FS and the EEOAE multicomponents are properties of normal cochlear mechanics in a healthy ear and that the FS is a manifestation of the multicomponents. The findings in this study strongly indicate that the FS of the EEOAE evoked by extracochlear electrical stimulation is generated by wave interaction in the cochlea. The similarity between the EEOAE FS and the DPOAE FS suggests that they may share the same mechanism.

Animals↗
PubMed2000

Three-dimensional numerical modeling for global cochlear dynamics.

A hybrid analytical-numerical model using Galerkin approximation to variational equations has been developed for predicting global cochlear responses. The formulation provides a flexible framework capable of incorporating morphologically based mechanical models of the cochlear partition and realistic geometry. The framework is applied for a simplified model with an emphasis on application of hybrid methods for three-dimensional modeling. The resulting formulation is modular, where matrices representing fluid and cochlear partition are constructed independently. Computational cost is reduced using two methods, a modal-finite-element method and a boundary element-finite-element method. The first uses a cross-mode expansion of fluid pressure (2.5D model) and the second uses a waveguide Green's-function-based boundary element method (BEM). A novel wave number approach to the boundary element formulation for interior problem results in efficient computation of the finite-element matrix. For the two methods a convergence study is undertaken using a simplified passive structural model of cochlear partition. It is shown that basilar membrane velocity close to best place is influenced by fluid and structural discretization. Cochlear duct pressure fields are also shown demonstrating the 3D nature of pressure near best place.

Auditory Perception↗
PubMed2000

The mechanical waveform of the basilar membrane. II. From data to models--and back.

Mechanical responses in the basal turn of the guinea-pig cochlea are measured with low-level broad-band noise as the acoustical stimulus [for details see de Boer and Nuttall, J. Acoust. Soc. Am. 101, 3583-3592 (1997)]. Results are interpreted within the framework of a classical three-dimensional model of the cochlea that belongs to a very wide class of nonlinear models. The use of linear-systems analysis for this class of nonlinear models has been justified earlier [de Boer, Audit. Neurosci. 3, 377-388 (1997)]. The data are subjected to inverse analysis with the aim to recover the "effective basilar-membrane impedance." This is a parameter function that, when inserted into the model, produces a model response, the "resynthesized" response, that is similar to the measured response. With present-day solution methods, resynthesis leads back to an almost perfect replica of the original response in the spatial domain. It is demonstrated in this paper that this also applies to the response in the frequency domain and in the time domain. This paper further reports details with regard to geometrical properties of the model employed. Two three-dimensional models are studied; one has its dimensions close to that of the real cochlea, the other is a stylized model which has homogeneous geometry over its length. In spite of the geometric differences the recovered impedance functions are very similar. An impedance function computed for one model can be used in resynthesis of the response in the other one, and this leads to global amplitude deviations between original and resynthesized response functions not exceeding 8 dB. Discrepancies are much larger (particularly in the phase) when a two-dimensional model is compared with a three-dimensional model. It is concluded that a stylized three-dimensional model with homogeneous geometric parameters will give sufficient information in further work on unraveling cochlear function via inverse analysis. In all cases of a sensitive cochlea stimulated by a signal with a stimulus level of 50 dB SPL per octave or less, the resulting basilar-membrane impedance is found to be locally active, that is, the impedance function shows a region where the basilar membrane is able to amplify acoustic power or to reduce dissipation of power by the organ of Corti. Finally, the influence of deliberate errors added to the data is discussed in order to judge the accuracy of the results.

Animals↗
PubMed2000

The mechanical waveform of the basilar membrane. III. Intensity effects.

Mechanical responses in the basal turn of the guinea-pig cochlea were measured with broad-band noise stimuli and expressed as input-output cross-correlation functions. The experiments were performed over the full range of stimulus intensities in order to try to understand the influence of cochlear nonlinearity on frequency selectivity, tuning, signal compression and the impulse response. The results are interpreted within the framework of a nonlinear, locally active, three-dimensional model of the cochlea. The data have been subjected to inverse analysis in order to recover the basilar-membrane (BM) impedance, a parameter function that, when inserted into the (linearized version of that) model, produces a model response that is similar to the measured response. This paper reports details about intensity effects for noise stimulation, in particular, the way the BM impedance varies with stimulus intensity. In terms of the underlying cochlear model, the decrease of the "activity component" in the BM impedance with increasing stimulus level is attributed to saturation of transduction in the outer hair cells. In the present paper this property is brought into a quantitative form. According to the theory [the EQ-NL theorem, de Boer, Audit. Neurosci. 3, 377-388 (1997)], the BM impedance is composed of two components, both intrinsically independent of stimulus level. One is the passive impedance Zpass and the other one is the "extra" impedance Zextra. The latter impedance is to be multiplied by a real factor gamma (0 < or = gamma < or = 1) that depends on stimulus level. This concept about the composition of the BM impedance is termed the "two-component theory of the BM impedance." In this work both impedances are entirely derived from experimental data. The dependence of the factor gamma on stimulus level can be derived by using a unified form of the outer-hair-cell transducer function. From an individual experiment, the two functions Zpass and Zextra are determined, and an approximation (Zpass + gamma Zextra) to the BM impedance constructed. Next, the model response (the "resynthesized" response) corresponding to this "artificial" impedance is computed. The same procedure is executed for several stimulus-level values. For all levels, the results show a close correspondence with the original experimental data; this includes correct prediction of the compression of response amplitudes, the reduction of frequency selectivity, the shift in peak frequency and, most importantly, the preservation of timing in the impulse response. All these findings illustrate the predictive power of the underlying model.

Animals↗
PubMed1999

The radial pattern of basilar membrane motion evoked by electric stimulation of the cochlea.

Electric current applied to the cochlea can evoke in situ electromotile responses of the organ of Corti. These nonsound-generated responses can give insight into the mechanics of the organ as the putative forces produced by outer hair cells (OHC) must couple to the modes of vibration of the basilar membrane (BM). In this study, platinum-iridium wire electrodes were positioned into the scala vestibuli and scala tympani of the first cochlear turn in the guinea pig. Current (1.5 ms rectangular-shaped pulses) was applied to these electrodes at levels to 500 microA peak. A laser Doppler velocimeter was used to record the velocity or displacement of the basilar membrane at the tonotopic 18 kHz place via an opening into the scala tympani of the first cochlear turn. Beads were positioned across the width of the BM so that the velocity or displacement of the BM could be studied in the radial direction. It was found that the current pulses evoked linear displacements of up to 2 nm for current levels of 500 microA (higher levels were damaging to the organ of Corti). The pattern of motion across the width of the BM was such that maximum displacement and velocity was located near the first row of OHCs and the position of the outer pillar cell footplate. The BM motion was biphasic in that the zona arcuata moved in the opposite direction to that of the zona pectinata. The results of this study demonstrate that the level of force produced by OHCs is effective in moving the BM and that the distribution of force within the organ of Corti leads to a multimodal motion pattern of the BM for this experimentally artificial means of evoking OHC motion.

Animals↗
PubMed1999

Membrane properties and the excitatory junction potentials in smooth muscle cells of cochlear spiral modiolar artery in guinea pigs.

Blood circulation changes in the inner ear play an important role in many physiological and pathological conditions of hearing function. The spiral modiolar artery (SMA) is the terminal artery to the cochlea. It was surrounded with nerve fibers immunostained by an antibody for tyrosine hydroxylase. By using intracellular recording techniques on the acutely isolated SMA, membrane properties of the smooth muscle cells and the neuromuscular transmission in this preparation were investigated. With minimum tension and normal extracellular K(+) concentration (5 mM), the majority of muscle cells showed a resting potential near -80 mV and an input resistance of about 8 MOmega. V/I plot showed an inward rectification in these cells. Barium (50-500 microM) caused strong depolarization and an increase in input resistance. Transmural electrical stimulation evoked stimulation intensity-dependent depolarizations (2-31 mV) following a short latency ( approximately 20 ms). The evoked potential by a low intensity stimulus was completely blocked by 1 microM tetrodotoxin. The potential and a depolarization induced by norepinephrine (10 microM) was usually partially (40-90%) blocked by alpha-receptor antagonists prazosin and/or idazoxan with concentrations up to 1 microM. Action potentials were observed when the depolarization was more than -40 mV. It is concluded that SMA smooth muscle cells, similar to those in other brain small arteries, highly express inward rectifying potassium channels; the cells receive catecholaminergic innervation, and stimulation of the nerves elicited an excitatory junction potential that is partially mediated by adrenergic receptors.

Animals↗
PubMed1999

The "inverse problem" solved for a three-dimensional model of the cochlea. III. Brushing-up the solution method.

In two earlier papers [de Boer, J. Acoust. Soc. Am. 98, 896-903 and 904-910 (1995)] the inherent problems of the inverse-solution method in cochlear mechanics were described. The present paper shows results obtained with a more universal solution method. With the new method it is possible to construct a three-dimensional model of the cochlea producing a response that accurately simulates a measured mechanical basilar-membrane response. With earlier methods this could not be done. The inverse solution invariably yields that, with low stimulus levels, the model simulating a viable cochlea must be locally active. For the response of a dead animal a passive model is sufficient. Once more the inherent intricacies and problems of the inverse-solution method are discussed. Conservation of fluid volume leads to the concept of the "virtual stapes velocity." For best results, the input signal to the inverse-solution procedure should be acquired in the form of a "composite cross-correlation spectrum." Inverse analysis can, under certain circumstances, produce aberrant results. In this paper it is shown why the resulting impedance function is the most accurate in the region of the response peak. Therefore, it is unlikely that a passive model would exist of which the response simulates the data obtained from a healthy animal.

Acoustic Stimulation↗
PubMed1998

Influence of intense sound exposure on glutathione synthesis in the cochlea.

Previous studies have shown that depletion of endogenous glutathione (GSH) potentiates noise-induced hearing loss (NIHL), whereas replenishment of GSH attenuates NIHL (Yamasoba et al., Brain Res. 784 (1998) 82-90). Since these findings indicate an important role of GSH in protection from NIHL, we assessed the influence of intense sound exposure (broadband noise, 105 dB SPL, 5 h) on GSH and cysteine levels in the guinea pig cochlea using high performance liquid chromatography. GSH levels were significantly increased in the lateral wall 2 and 4 h post-exposure and returned to normal 6 h post-exposure. GSH levels in the sensory epithelium and modiolus did not show significant changes following noise. Cysteine levels were unchanged in any of the cochlear segments. For the cochlea as a whole, intense sound exposure did not significantly change GSH or cysteine levels throughout the 6-h measurement period post-exposure. These results indicate that GSH synthesis is markedly upregulated selectively in the lateral wall by noise exposure, presumably in response to the robust consumption of GSH, as it is utilized in scavenging reactive oxygen species.

Animals↗
PubMed1998

Role of glutathione in protection against noise-induced hearing loss.

A potential mechanism of hearing loss due to acoustic overstimulation is the generation of reactive oxygen species (ROS). ROS not removed by antioxidant defenses could be expected to cause significant damage to the sensory cells of the cochlea. We studied the influence of the antioxidant glutathione (GSH) on noise-induced hearing loss by using l-buthionine-[S,R]-sulfoximine (BSO), an inhibitor of GSH synthesis, and 2-oxothiazolidine-4-carboxylate (OTC), a cysteine prodrug, which promotes rapid restoration of GSH when GSH is acutely depleted. Pigmented female guinea pigs were exposed to broadband noise (102 dB SPL, 3 h/day, 5 days) while receiving daily injections of BSO, OTC, or saline. By weeks 2 and 3 after noise exposure, BSO-treated animals showed significantly greater threshold shifts above 12 kHz than saline-treated subjects, whereas OTC-treated animals showed significantly smaller threshold shifts at 12 kHz than controls. Histologically assessed noise-induced damage to the organ of Corti, predominantly basal turn row 1 outer hair cells, was most pronounced in BSO-treated animals. High performance liquid chromatographic analysis showed that OTC significantly increased cysteine levels, but not GSH levels, in the cochlea. These findings show that GSH inhibition increases the susceptibility of the cochlea to noise-induced damage and that replenishing GSH, presumably by enhancing availability of cysteine, attenuates noise-induced cochlear damage.

Animals↗
PubMed1998

Endolymphatic hydrops reduces retrograde labeling of trigeminal innervation to the cochlea.

This paper reports that endolymphatic hydrops causes a significant reduction of retrogradely labeled cell bodies of the ipsilateral trigeminal ganglion following application of horseradish peroxidase in the cochlea. We previously showed that the trigeminal ganglion is a source of primary sensory innervation to the cochlear blood vessels. The innervation of the cochlea from the trigeminal ganglion may provide the basis of an alternative mechanism for Ménière's syndrome (imbalance, hearing loss, tinnitus, and a sensation of fullness in the ear) for which a central neural basis has been speculated. Innervation patterns of sensory nerves from the trigeminal ganglion to the cochlear blood vessels were studied using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Healthy and hydropic guinea pigs were unilaterally implanted with an osmotic pump and a cannula for cochlear delivery of 2% WGA-HRP or vehicle alone. In other guinea pigs the cochlea was pretreated with 100 micromol capsaicin before administering 2% WGA-HRP. Histological sections of the ipsi- and contralateral trigeminal ganglia were obtained 48 h after WGA-HRP infusion. In the hydropic guinea pig, the number of labeled nerve cell bodies observed in the anteriomedial portion of the trigeminal ganglion at the origin of the ophthalmic nerve was reduced by 70% relative to normal animals. Capsaicin pretreatment nearly eliminated the labeled sensory fibers as expected. These data indicate that the trigeminal innervation to the cochlea could be involved in inner ear homeostatic disturbances, including the hydrops that is symptomatic of Ménière's disease.

Animals↗
PubMed1998

The vascular mechanism of action of betahistine in the inner ear of the guinea pig.

The aim of this study was to investigate the mechanism and site of action of betahistine dihydrochloride in the inner ear of the guinea pig. Betahistine-evoked increases in cochlear blood flow (CBF) have been presumed to be due to the drug effect on the later wall capillary bed or larger feeding vessels in the cochlea vascular system. As such, the mechanism of action could be due to inhibition of H3 receptors. Betahistine may also have a direct effect on postsynaptic H1/H2 receptors and/or an effect modulated by other autonomic receptors. Betahistine-evoked CBF responses were assessed by laser Doppler flowmetry in the presence of an H3 agonist (alpha N-methyl-histamine dihydrochloride), an H3 antagonist (thioperamide), an H2 antagonist (cimetidine) or an alpha 2 antagonist (idazoxan). The effects of betahistine on circulation in the anterior inferior cerebellar artery (AICA) and ipsilateral stria vascularis (SV) were assessed using intravital microscopy (IVM). Findings showed that betahistine increased CBF and reduced systemic blood pressure (BP). In contrast, alpha N-methylhistamine dihydrochloride had no effect on baseline CBF or BP and did not influence betahistine-induced increases in CBF. Thioperamide reversed the effects of betahistine on CBF, but had no effect on baseline CBF or BP. Cimetidine had no marked effect on baseline CBF or betahistine-induced increases in CBF Idazoxan had no consistent effects on baseline CBF, but abolished the effect of betahistine on CBF. The mean increase of red blood cell velocity in SV capillaries was 15% and occurred without a demonstrable change in capillary diameters. In contrast, the diameter of the AICA increased by 17-20%, indicating that betahistine-evoked increases in CBF resulted primarily from vasodilatation of the AICA. We suggest that this effect may be mediated via presynaptic H3 heteroreceptors and autonomic alpha 2 receptors.

Animals↗
PubMed1998

Direct evidence of trigeminal innervation of the cochlear blood vessels.

This paper provides the first detailed description of the trigeminal innervation of the inner ear vasculature. This system provides a newly discovered neural substrate for rapid vasodilatatory responses of the inner ear to high levels of activity and sensory input. Moreover, this discovery may provide an alternative mechanism for a set of clinical disturbances (imbalance, hearing loss, tinnitus and headache) for which a central neural basis has been speculated. Iontophoretic injections of biocytin were made via a glass microelectrode into the trigeminal ganglion in guinea-pigs. Tissue for histological sections was obtained 24 h later. Labeled fibers from the injection site were observed as bundles around the ipsilateral spiral modiolar blood vessels, as individual labeled fibers in the interscala septae, and in the ipsilateral stria vascularis. The dark cell region of the cristae ampullaris in the vestibular labyrinth was also intensively labeled. No labeled fibers were observed in the neuroepithelium of the cristae ampullaris or the semicircular canals. These results confirm and localize an earlier indirect observation of the trigeminal ganglion projection to the cochlea. This innervation may play a role in normal vascular tone and in some inner ear disturbances, e.g., sudden hearing loss may reflect an abnormal activity of trigeminal ganglion projections to the cochlear blood vessels.

Animals↗
PubMed1998

Changes in cochlear blood flow due to intra-arterial infusions of angiotensin II (3-8) (angiotensin IV) in guinea pigs.

The effects of a newly discovered form of angiotensin, angiotensin IV (ANGIV), on cochlear blood flow (CBF) have been investigated utilizing the laser Doppler flowmetry (LDF) technique. Two specific questions were addressed: What are the effects of anterior inferior cerebellar artery infusions (AICA) of ANGIV on CBF and do angiotensin fragments other than ANGIV influence CBF in mature male and female guinea pigs. Infusions of ANGIV, and C-terminal shortened fragments were accomplished via micropipette into the AICA and changes in CBF were observed using LDF. The results demonstrated that 10 and 100 pmol/min doses of ANGIV increased CBF 22% and 75% (n = 6; P < 0.01) from baseline, respectively, with little change in mean arterial blood pressure (MAP). Pretreatment with the ANGIV antagonist divalanal-ANGIV (1 nmole/min) blocked increases in CBF due to infusions of 100 pmol/min of ANGIV. The infusion of the C-terminal shortened fragment ANGIV(1-5) and saline had no significant effect on either CBF or MAP. These results provide the evidence for a new subtype of the angiotensin receptor and indicate the likely role of circulating hormones in blood flow regulation in the inner ear.

Amino Acid Sequence↗
PubMed1998

Acoustical modulation of electrically evoked otoacoustic emission in intact gerbil cochlea.

In order to study the interaction between mechanical-electrical and electrical-mechanical transductions of outer hair cells (OHCs) in vivo, we observed the acoustically induced changes in the electrically evoked otoacoustic emission (EEOAE). One pole of a bipolar electrode was placed in the round window niche and the other pole on the surface of the first cochlear turn in the gerbil. A microphone and a speaker were used to monitor the EEOAE and to deliver an acoustical tone, respectively. It was found that a high sound level acoustical tone enhanced the EEOAE fine structure at frequencies below the acoustical frequency, and suppressed the overall level of the EEOAE at frequencies above the acoustical frequency. In addition, the EEOAE at frequencies approximately one half octave lower than the acoustical frequencies were relatively more enhanced or showed relatively less suppression than at other frequencies. The amplitudes of these changes had a positive relationship with acoustical tone levels. Furosemide eliminated the acoustically caused EEOAE change indicating that the acoustically caused change in the EEOAE is a phenomenon of the normal cochlea. One possible mechanism for the results is that the electrically and acoustically evoked basilar membrane (BM) vibrations interact at the EEOAE generation site and change the local mechanical and electrical properties. The second possible mechanism is that the acoustical stimulus creates an impedance discontinuity at its characteristic frequency location leading to a change in the reflected electrically evoked traveling wave, which may enhance or suppress the EEOAE by the vector summation of two waves.

Acoustic Stimulation↗
PubMed1998

Age-related changes in cochlear blood flow response to occlusion of anterior inferior cerebellar artery in mice.

Previous studies suggest that autoregulation of cochlear blood flow (CBF) may be impaired by aging. In this study, we quantified the capacity of CBF autoregulation in young adult (6-month-old) and aged (21-month-old) CBA mice, to examine the effect of aging on CBF autoregulation. The technique of anterior inferior cerebellar artery (AICA) occlusion was employed to manipulate cochlear perfusion pressure. The CBF was measured by laser Doppler flowmetry during intermittent occlusion of the AICA with a microvascular clamp, which causes an initial decrease in CBF. The autoregulation of CBF was evaluated by quantifying the CBF increase (compensatory dilatory response in the cochlear vessels) during AICA occlusion. Our results demonstrated that autoregulation of CBF was significantly reduced and that collateral vascular function supplying CBF was significantly lower in the aged group. These findings suggest that the aged ear has less capacity to maintain stable blood flow and thus may be more vulnerable to stress factors that affect cochlear function.

Age Factors↗
PubMed1997

Trigeminal ganglion innervation of the cochlea--a retrograde transport study.

Innervation patterns of sensory nerves from the trigeminal ganglion to the cochlear blood vessels were studied using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Guinea-pigs (n=7) were unilaterally implanted with an osmotic pump and a cannula for cochlear delivery of 2% or 20% wheat germ agglutinin horseradish peroxidase (Group 1), 2% wheat germ agglutinin-horseradish peroxidase followed by 100 micromol capsaicin (Group 2), or vehicle alone. Histological sections of the trigeminal ganglia, the C1 and C2 dorsal ganglia, the superior and inferior ganglia of the glossopharyngeal nerve bilaterally, the midbrain and the brainstem were obtained after 48 h of infusion. In Group 1, a large number of labeled nerve cell bodies were observed in the anteromedial portion of the trigeminal ganglion and at the origin of the ophthalmic nerve. Some labeled cells were also found on the lateral side of the ophthalmic nerve, as well as on the medial side of the maxillary nerve root. Capsaicin pretreatment significantly reduced the density of labeled neurons in the trigeminal ganglion. A few labeled neurons were also found in the trigeminal brainstem nucleus complex and in certain auditory brainstem nuclei. No wheat germ agglutinin horseradish peroxidase-positive cells were observed in the spinal C1 or C2 cervical ganglia or in the superior or inferior glossopharyngeal ganglia. In contrast, wheat germ agglutinin-horseradish peroxidase application to the middle ear resulted in labeled cells in the middle posterolateral portion of the trigeminal ganglia and in the superior ganglia of the glossopharyngeal nerve. These results provide the first direct evidence that the trigeminal ganglion sends projections to the cochlea.

Animals↗