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Distortion product otoacoustic emissions in human hypercholesterolemia.

Epidemiological and experimental studies suggest that hypercholesterolemia promotes the development of sensorineural hearing loss; however, the underlying cellular pathomechanism remains obscure. In the present study, 20 healthy subjects and 20 patients with familial hypercholesterolemia were compared with respect to their hearing function. None of the 40 persons reported any history of hearing disorder. In accordance with this subjective impression, mean hearing thresholds were within the normal, age-dependent ranges in both groups. In contrast, the single-generator distortion product otoacoustic emissions (sgDPOAE) were reduced at and above 4 kHz. Input-output functions of DPOAE could be subdivided into three groups: (i) normal, with unity slope at low intensities and slope less than unity (0.24+/-0.07 dB/dB at higher intensities; (ii) pathologic, described by a single straight line; (iii) ill-defined, with data usually indistinguishable from the background noise level. The ill-defined DPOAE behavior was only found in patients with hypercholesterolemia; namely, for 25% of patients at f(2)=1.5 kHz and for 50% at f(2)=4 kHz. Patients belonging to the pathologic and ill-defined DPOAE groups had significantly (P<0.05) higher total serum cholesterol and LDL-cholesterol levels compared with subjects from the normal DPOAE group. While hearing thresholds of patients with ill-defined growth functions were not statistically different from those of normal subjects, speech scores were significantly reduced in these cases. The data imply that nonlinear mechanical processes in the cochlea are compromised in hypercholesterolemic patients.

Adult↗

PPADS, an ATP antagonist, attenuates the effects of a moderately intense sound on cochlear mechanics.

Increasing attention is being given to the role of neurotransmitters and other signaling substances in the damage induced by intense sound to the cochlea. Adenosine triphosphate (ATP) is one example of a putative neurotransmitter that may alter cochlear mechanics during sound exposure. The purpose of the present study was to test the hypothesis that endogenous extracellular ATP has a role in the generation of the changes in cochlear mechanics induced by moderate intense sound exposure. Guinea pigs were exposed to either: (1) a perilymphatic administration of pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 1 mM), an ATP antagonist; (2) a moderately intense sound (6 kHz tone, 95 dB SPL, 15 min); or (3) a combination of the PPADS and the sound. The effects on the cubic distortion product otoacoustic emissions (DPOAEs; 2f1-f2) were monitored using three sets of equal level primaries (f1=9.25 kHz, f2=10.8 kHz, 2f1-f2=7.7 kHz; f1=7.2 kHz, f2=8.4 kHz, 2f1-f2=6 kHz; f1=5.55 kHz, f2=6.5 kHz, 2f1-f2=4.6 kHz). PPADS alone had no effect on the cubic DPOAEs monitored. The intense sound alone suppressed all three cubic DPOAEs. The combination of PPADS with the intense sound induced a suppression of the cubic DPOAEs that was equal to or greater than induced by the intense sound alone at f2=10.8 kHz but was equal to or less than induced by the intense sound at f2=8.4 and 6.5 kHz. After washing the PPADS out of the cochlea with artificial perilymph, all three cubic DPOAEs were suppressed less in the PPADS with intense sound treatment group than in the intense sound alone group. The PPADS appeared to provide protection from the intense sound. Results are consistent with the hypothesis that extracellular ATP is involved in the changes in cochlear mechanics induced by moderately intense sound exposure.

Adenosine Triphosphate↗

Time estimation ability and distorted perception of sleep in insomnia.

Although it is an established finding that people with insomnia characteristically overestimate the time they have taken to get to sleep and underestimate the total amount of time they have slept, little is known about the mechanisms that underpin this phenomenon. Accordingly, this study sought to investigate whether the tendency to misperceive sleep among patients with insomnia is accounted for by (a) a general deficit in time estimation ability or (b) the context in which the time estimates are made. Twenty individuals with insomnia and 20 individuals who did not have insomnia were asked to perform two time estimation tasks; one in the laboratory during the day and one in the participant's own bedroom during the night. The two groups were compared with respect to the accuracy of their performance in estimating unfilled temporal intervals of various lengths. The results indicated that the performance of the insomnia group was no different from that of the noninsomnia group, regardless of the context in which the time estimates were made. Time overestimation correlated positively with cognitive and physiological arousal experienced during the time estimation tasks. These findings argue against the hypothesis that individuals with insomnia misperceive their sleep simply because they are poor estimators of time. Future research is required to test the hypothesis that increased cognitive arousal (worry) and physiological arousal are candidate mechanisms that underpin sleep misperception.

Adult↗

[Use of acoustic distortion products in clinical diagnosis. The site of origin of otoacoustic emissions in the inner ear].

Distorsion product otoacoustic emissions (DPOAE) are generated by a continuous bitonal stimulation of the cochlea. The resulting emissions are measurable in a definite mathematical function of the primaries (mf1 +/- nf2; f1 < f2). In humans sound emission at the frequency 2f1-f are usually detectable. To determine if a disturbance of DPOAE-amplitude is associated with a cochlear lesion in the frequency region of the evoked emissions or the primaries, we performed suppression experiments using normal-hearing, healthy probands (n = 14). DPOAE were measured in the frequency range between 800 Hz and 8 kHz with different sound-pressure levels for the primaries. Evoked emissions for each proband were measured with these different stimulus parameters to determine baseline values. In suppression experiments sound emissions were evoked continuously with different stimuli between 800 Hz and 8 kHz, disturbed simultaneously with a third tone of 1, 2 and 4 kHz and then compared with baselines. Suppressor tones (1, 2, 4 kHz) reduced significantly the DPOAE amplitudes in the frequency region of the geometric mean of the primaries. This indicates that a reduction of the emission amplitude in associated with a cochlear lesion near the generation site of the DPOAE. The suppression curves exhibit a sharp and steep graph, indicating their relation to cochlear frequency selectivity.

Acoustic Stimulation↗

Antioxidant status and hearing function in noise-exposed workers.

The cellular antioxidant system appears to protect cochlear hair cells from oxidative stress due to noise and aging. The role of individual metabolic variables remains poorly understood, however. We examined the role of a number of metabolic factors on human cochlear function in noise-exposed individuals. In 58 factory workers we measured audiometry and distortion product otoacoustic emissions prior to a workshift. Simultaneously we measured levels of vitamin E, vitamin C, and polymorphism status for two metabolic genes related to glutathione S-transferase function (GSTM1 and GSTT1). Age and total noise exposure were predictive of hearing status. Vitamin E levels were negatively correlated with hearing function, and this effect was partly explained by an increase in vitamin E levels with age. No effect was found for vitamin C. Individuals possessing the GSTM1 gene had significantly better high frequency otoacoustic emissions compared to GSTM1 null individuals. The protective effect of GSTM1 was present even after adjusting for age, race, sex, and years of noise exposure. GSTT1 did not exhibit a similarly protective effect. While the cross-sectional nature of the study precludes drawing conclusions about causation, these data suggest that GSTM1, an antioxidant enzyme which is found in the mammalian cochlea, may play a protective role in humans against hair cell damage due to noise or aging.

Adult↗

The dominance of touch by vision: sometimes incomplete.

It is generally agreed that, when the two senses are in conflict, vision dominates touch. In the series of experiments reported here the discrepancy between the visual and the haptic images was progressively increased. In each experiment half of the observes were adults and half children, and half of each group wore a glove which concealed the distortion produced by the lens. In experiment 1 the visual image of a haptic square was transformed by a week or strong cylindrical lens so that the sides were in the ratio 1:1.5 or 1:1.8. Gloved observers selected a comparison image close to the visual image. Bare-handed observers gave compromise judgements with the strong lens, but judgements similar to those of the gloved observers with the weak lens. In experiment 2 the square had a visual image which was either a diamond or a parallelogram, the parallelogram having angles of 70 degrees and 110 degrees. Observers described and drew their percepts, which were generally in accord with the visual image. There were no significant differences due to age, a finding contrary to that of Page and Locke, nor were there differences in experiment 2 due to the gloved-hand-bare-hand dimension. It is concluded (i) that repeated observations do not destroy the effect, (ii) tht considerable discrepancies between the visual and haptic images do not destroy the effect, but (iii) that feedback from a bare hand can reduce the effect when it is of considerable magnitude.

Adult↗

[Suppression tuning characteristics of the 2f1-f2 distortion product in cochlear microphonics and otoacoustic emissions].

Suppression of the 2f1-f2 distortion product (DP) by the third tone was measured in cochlear microphonics (CM) and otoacoustic emissions (OAEs) in guinea pigs to clarify the generation site of the DPs. The DPs were elicited by the primary tones with frequencies of 4.62 kHz (f1) and 6 kHz (f2). Five dB-iso-suppression tuning curves (STCs) of the DPs were obtained by plotting the suppressor level as a function of its frequencies. The STCs in both CM DP and DPOAE had the shape of the letter "V" with the tip centering around the frequency of f2. The slopes of the STC on the higher frequency side were steeper than those on the lower side. As the intensity of the primary tones was decreased, the turning of the STC became sharper. These suppression properties indicate that the 2f1-f2 DPs were generated in the area on the basilar membrane where the characteristic frequency corresponded to those of primary tones, especially for the primaries at lower intensities. Because the suppression properties in CM DP and DPOAE were similar to each other, we concluded that these two phenomena had a common generation site.

Acoustic Stimulation↗

Reorganization of perception: a Konorskian interpretation of the Innsbruck experiments.

This paper discusses the close fit of Konorski’s model to the data of Kohler’s Innsbruck experiments and also to more recent neurophysiological studies of environmental surgery or sensory disturbances. The dramatic Innsbruck research using special goggles or prismatic glasses that reversed or distorted the visual field confirmed and extended Stratton's earlier use of the substitution method. The subjects had at first insuperable difficulties in their locomotor behavior if it was guided by vision. After practice guided by certain rules, they were able to perform and eventually to "see" correctly in the strange environment. These studies demonstrate the plasticity of the nervous system, even in the adult. The problem for the field is to determine how these new associations, antagonistic to long established conditioned reflexes (CRs), become functional. The particular questions arise: what rules impede, what rules facilitate the transformation of CRs, and what physiological mechanism is responsible for the changed relations between the organism and the external world? Konorski’s remarkable theory is that no transformations of connections occurs in the reversal training. Instead, what actually happens is the formation of a connection between the original instrumental CR and non-reinforcement, and actualization of excitatory connections between the CS units and the kinesthetic units of the antagonistic movement. If correct, this motor act marks the termination of the eliciting drive and is reinforced. The original CR is readily re-established by restitution of its reinforcement.

Adaptation, Physiological↗

Optimum primary tone level setting for measuring high amplitude DPOAEs in guinea pigs.

A special stimulus paradigm needs to be applied when distortion product otoacoustic emission (DPOAE) input/output functions are used to investigate the loss of sensitivity and loss of compression of outer hair cell cochlear amplifiers during noise exposure, drug treatment, etc. This stimulus paradigm should be able to reflect cochlear non-linear compressive sound processing known from direct basilar membrane measurements. Such a paradigm has already been established for humans that accounts for the different compression of the primary tones at the DPOAE generation site at f2 with L1 = 0.4 L2 + 39 dB SPL ('scissor paradigm'). The purpose of the present study was to develop an equivalent parameter setting for guinea pigs. Ninety-six different L1 - L2 combinations were presented to 24 ears in 18 pigmented guinea pigs at seven f2 frequencies between 2 and 16 kHz. L2 ranged from 20 to 60 dB SPL, L1 from 20 to 65 dB SPL. An extreme value analysis was performed to achieve the maximum DPOAE level for L1 in relation to L2. Linear regression analysis yielded a scissor paradigm specific to guinea pigs (L1 = 0.46 L2 + 41 dB SPL) which is similar to that of humans.

Acoustic Stimulation↗

Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss.

Rats were exposed to ethyl benzene at 0, 300, 400 and 550 ppm for 8 hours/day for 5 consecutive days. Three to six weeks after the exposure, auditory function was tested by measuring compound action potentials (CAP) in the frequency range of 1-24 kHz and 2f1-f2 distortion product otoacoustic emissions (DPOAEs) in the frequency range of 4-22.6 kHz. In addition, outer hair cell (OHC) loss was quantified by histological examination. The lowest concentration ethyl benzene had no effect on any of the above measures. At 400 ppm, auditory thresholds were increased by 15 and 16 dB at 12 and 16 kHz, respectively, and at 550 ppm by 24, 31, and 22 dB at 8, 12, and 16 kHz, respectively. DPOAE amplitude growth with stimulus level was affected only after 550 ppm at 5.6, 8, and 11.3 kHz. OHC loss was found in two of the five examined locations in the cochlea. At 400 ppm, 25% OHC loss was found at the 11- and 21-kHz region. The highest concentration evoked 40% and 75% OHC loss at the 11- and 21-kHz location, respectively. Thus, the mid-frequency region of rats is affected after exposure to relatively low concentrations of ethyl benzene (400-550 ppm). These results indicate that ethyl benzene is one of the most potent ototoxic organic solvents known today.

Action Potentials↗

Influence of spontaneous otoacoustic emissions (SOAE) on acoustic distortion product input/output functions: does the medial efferent system act differently in the vicinity of an SOAE?

Otoacoustic emission (OAE) generation mechanisms reside in the active micromechanical properties of the organ of Corti, and especially in the outer hair cells (OHCs). OHCs are strongly innervated by medial efferent olivo-cochlear fibres. Decrease of the intensity of transiently evoked otoacoustic emissions (TOAEs) and modification of spontaneous otoacoustic emissions (SOAEs) during acoustic stimulation of the contralateral ear have already been shown in humans. Similar results were obtained in guinea pigs with a decrease of 2F1-F2 acoustic distortion products (DPOAEs) and a suppression of the effect with sectioning of the floor of the fourth ventricle. The present study sought to investigate the influence of contralateral auditory stimulation on DPOAEs recorded in humans. It shows a decrease in DPOAE intensity for all frequencies, at levels above 45 dB SPL of contralateral broad band noise. This effect was found at levels of contralateral BBN well below the acoustic reflex threshold, and in subjects without acoustic reflex. Moreover, the influence of transcranial transmission could be ruled out since no effect was found when contralateral BBN applied to the altered ear of totally unilaterally deaf patients. Thus, the contralateral acoustic stimulation effect on DPOAEs provides a new means of functional exploration of the medial efferent system in humans. The effect obtained is more ample at low primary frequency levels. Moreover, as DPOAEs are known to be stronger and to show more irregular input/output function patterns in the vicinity of an SOAE, the influence of contralateral auditory stimulation was studied for DPOAEs recorded at 10 Hz, 50 Hz and 150 Hz from an SOAE frequency.

Acoustic Stimulation↗

Replacing the Amsler grid: a new method for monitoring patients with age-related macular degeneration.

PURPOSE: To investigate a method that uses hyperacuity, the Macular Computerized Psychophysical Test (MCPT), to evaluate the central macular visual field in patients with age-related macular degeneration (AMD). DESIGN: Prospective case-control study of a diagnostic test. PARTICIPANTS AND CONTROLS: One hundred eight eyes of 108 Patients with AMD and 51 eyes of 51 age-matched patients with no retinal disease. Patients with AMD included 32 (30%) patients with choroidal neovascularization (CNV), 23 (21%) with geographic atrophy (GA), 35 (32%) with AMD with high-risk characteristics (HRC), and 18 (17%) with early AMD with non-HRC. TESTING: Each subject underwent the MCPT, in which a virtual line composed of dots (white dots on a black background, maximal contrast) is flashed across different macular loci to a perifoveal radius of 7 degrees. Patients' responses were recorded and automatically analyzed using a specific algorithm developed before the onset of the study. All patients also underwent a supervised Amsler grid examination on the encounter before or after the MCPT in random order. MAIN OUTCOME MEASURES: Distortion, scotoma, or blurring perceived by the patient after a swift change of fixation was considered positive on the MCPT. Any perception of distortion, scotoma, or blurring was considered positive on the Amsler grid. RESULTS: Of the 32 patients with CNV, 30 (94%) were found positive on the MCPT and 11 (34%) were found positive on the Amsler grid. Of the 23 GA patients, 21 (91%) were found positive on the MCPT and 7 (30%) were found positive on the Amsler grid. Of the 35 HRC patients, 28 (80%) were found positive on the MCPT and 3 (9%) were found positive on the Amsler grid, and of the 18 early AMD with non-HRC patients, 8 (44%) were found positive on the MCPT and 3 (17%) were found positive on the Amsler grid. Of the 51 controls, 3 (6%) were positive on the MCPT and 1 (2%) was positive on the Amsler grid. CONCLUSIONS: The MCPT was superior to the Amsler grid in detecting AMD-related lesions in this cohort. Studies are underway to determine whether the MCPT is feasible for home monitoring to provide early detection of progression to CNV.

Aged↗

Maturation of the human cochlear amplifier: distortion product otoacoustic emission suppression tuning curves recorded at low and high primary tone levels.

The cochlear amplifier shows level-dependent function and works optimally at low levels. For this reason, manipulation of stimulus level is a route through which the human cochlear amplifier can be investigated in a noninvasive manner. Distortion product otoacoustic emissions (DPOAEs) evoked as a function of stimulus level provide a tool for exploration of human cochlear amplifier function and, when applied to neonates, for investigation of cochlear maturation. The current experiment generated 2f1-f2 DPOAE ipsilateral suppression tuning curves (STCs) at three primary tone levels and five f2 frequencies in a large group of premature and term neonates and adults. The differences between tuning generated with low- and high-level primary tones was measured to provide a gross estimate of the "tuning enhancement effect" attributed to the cochlear amplifier. Other features of the DPOAE suppression tuning curves were measured as well. Consistent with previous reports, at 1500 and 6000 Hz, STCs were narrower, with a steeper slope on the low-frequency flank of the tuning curve in premature neonates versus adults. Additionally, only DPOAE STCs from adults and term neonates became markedly broader and more shallow when recorded with high-level primary tones. It has been hypothesized that the excessive narrowness of suppression tuning and the absence of a level effect on DPOAE STCs recorded in premature neonates reflects a subtle immaturity in cochlear amplifier function just prior to term birth.

Acoustic Stimulation↗

Time-frequency analyses of transient-evoked stimulus-frequency and distortion-product otoacoustic emissions: testing cochlear model predictions.

Time-frequency representations (TFRs) of otoacoustic emissions (OAEs) provide information simultaneously in time and frequency that may be obscured in waveform or spectral analyses. TFRs were applied to transient-evoked stimulus-frequency (SF) and distortion-product (DP) OAEs to test cochlear model predictions. SFOAEs and DPOAEs were elicited in 18 normal-hearing subjects using gated tones and tone pips. Synchronous spontaneous (SS) OAEs were measured to assess their contributions to SFOAEs and DPOAEs. A common form of TFR of measured OAEs was a collection of frequency-specific components often aligned with SSOAE sites, with each component characterized by one or more brief segments or a single long-duration segment. The spectral envelope of evoked OAEs differed from that of the evoking stimulus. Strong emission regions or cochlear "hot spots" were detected, and sometimes accounted for OAE energy observed outside the stimulus bandwidth. Contributions of hot spots and multiple internal reflections to the OAE, and differences between measured and predicted OAE spectra, increased as stimulus level decreased, consistent with level-dependent changes in the estimated cochlear reflectance. Suppression and frequency-pulling effects between components were observed. A recursive formulation was described for the linear coherent reflection emission theory [Zweig and Shera, J. Acoust. Soc. Am. 98, 2018-2047 (1995)] that is well suited for time-domain calculations.

Acoustic Stimulation↗

Detection of geometric image distortions at various eccentricities.

PURPOSE: Human ability to perceive spatial stimuli declines with increasing eccentricity. To study this phenomenon with natural images, the authors applied the spatial scaling method by measuring the smallest detectable amount of geometric change in a human face at several eccentricities for a series of stimulus magnifications to find out whether performance could be made equal across the visual field simply by an appropriate enlargement. METHODS: The authors used a novel method to produce subtle changes to an image of a face. The smallest change recognized was determined using a two-alternative forced-choice method and expressed in terms of correlation sensitivity, the inverse of the correlation between the images that just could be discriminated. RESULTS: The detection of changes in the facial features, presumably a spatially complex task, became equal across the visual field simply by an appropriate change of scale. The E2 value represents the eccentricity at which the foveal stimulus size must double to maintain performance at the foveal level. The E2 values, found to be 1.73 degrees to 2.45 degrees, were similar to our previously measured values for vernier acuity, orientation discrimination, and curvature detection and discrimination, obtained with the same method of spatial scaling. CONCLUSIONS: The authors' results indicate that with adequate stimulus magnification, one is capable of detecting geometric changes in complex images such as face equally at the fovea and in the periphery. In this task, there seems to be no qualitative difference between the accuracy of foveal and peripheral processing.

Face↗

Physiological vulnerability of distortion product otoacoustic emissions from the amphibian ear.

The physiological vulnerability of distortion product otoacoustic emissions (DPOAEs) was investigated in the leopard frog, Rana pipiens pipiens. For each frog, DPOAEs were recorded from the amphibian and the basilar papillae. Measurements were taken before and after either the arrest of oxygen supply due to cardioectomy, or the destruction of the central nervous system (CNS). DPOAEs in response to high-level stimuli (> 75 dB SPL) were rather robust to these insults during the first two hours post surgery. In contrast, DPOAE amplitudes in response to low-level stimuli (< 75 dB SPL) decreased significantly. On average, low-level emissions from the amphibian papilla disappeared within 6 min for cardioectomy, and after 13 min for CNS destruction. In the basilar papilla, low-level DPOAEs disappeared more slowly: on average after 34 min following cardioectomy, and after 58 min for CNS destruction. The difference in physiological vulnerability between low- and high-level emissions is similar to that in mammals and a lizard. The difference between the DPOAE decay rate of the frog's amphibian and basilar papillae suggests important differences between the hearing mechanisms of the papillae.

Acoustic Stimulation↗

Incomplete recovery of chicken distortion product otoacoustic emissions following acoustic overstimulation.

Distortion product otoacoustic emissions (DPOAEs) were measured in chickens before and after exposure to a 525-Hz pure tone (120 dB SPL, 48 h). The exposure caused extensive hair cell loss and destroyed the tectorial membrane along the abneural edge of the basilar papilla in the low-to-mid-frequency region of the cochlea. Although the lesion was restricted, DPOAEs were greatly depressed at all frequencies immediately after the exposure. The high-frequency DPOAEs gradually recovered to preexposure values after the exposure; however, there was little or no improvement in DPOAEs at test frequencies equal to or slightly above the exposure frequency even after 16 weeks of recovery. By 28 days of recovery, the previously damaged region of the basilar papilla had been repopulated by hair cells and the lower honeycomb layer of the tectorial membrane had regenerated, but not the upper fibrous layer. The upper fibrous layer of the tectorial membrane was still missing after 16 weeks of recovery and the region of damage corresponded closely to the frequency regions where the DPOAEs were depressed.

Acoustic Stimulation↗

Excitotoxic effect of kainic acid on chicken otoacoustic emissions and cochlear potentials.

Kainic acid (KA) is a potent glutamate analog that can temporarily or permanently damage glutamatergic neurons. The purpose of the present study was to determine the short- and long-term effects of KA on chicken otoacoustic emissions and cochlear potentials. A chronic electrode was used to record the compound action potential (CAP), cochlear microphonic (CM), and the slow, positive neural potential (SPNP), a predominantly dc response. The CM, CAP, SPNP, and distortion product otoacoustic emissions (DPOAEs) were recorded before and after infusing 10 microl of a low dose (KA-L, 0.3 mM) or high dose (KA-H, 5 mM) of KA into scala tympani. KA caused a rapid and large reduction in CAP and SPNP amplitude in both the KA-H and KA-L groups; however, the CM and DPOAEs were largely unchanged. The amplitude of the CAP and SPNP in the KA-L group began to recover around 1 week post-KA, but was approximately 50% below normal at 4 weeks post-KA. In contrast, the CAP and SPNP showed no signs of recovery in the KA-H group. The results suggest that KA has no effect on the CM and DPOAEs generated by the hair cells, but selectively damages the CAP generated by the cochlear ganglion neurons. The reduction in the avian SPNP suggests that the response originates in the cochlear afferent neurons, unlike the summating potential (SP) in mammals that is generated in hair cells.

Action Potentials↗