The evaluation of cochlear frequency analysis in the clinic.
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Biomedical subjects
Publications and source records attributed to R V Harrison.
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Human AP tuning curves (tone on tone simultaneous and forward masking curves) were measured during transtympanic electrocochleography. For subjects with near normal thresholds, average Q10 dB values (simultaneous masking) were 2.3 at 2 kHz, 3.6 at 4 kHz, and 4.7 at 8 kHz. Patients with threshold elevations of more than 40 dB, resulting from sensorineural hearing loss of cochlear origin, had tuning curves less sharply tuned by a factor of 2-3, with Q10 dB values of 1-2 at 2 kHz and at 4 kHz, and 1-2.3 at 8 kHz. AP tuning curves and single fibre tuning curves (frequency threshold curves) were measured in normal guinea pigs; cochlear fibre tuning is sharper than AP tuning (simultaneous masking) by a factor of 1.8 (2-20 kHz). Assuming that this factor can be applied to the human cochlea, estimates of normal human cochlear fibre Q10 dB values are 4.2 at 2 kHz, 6.5 at 4 kHz, and 8.5 at 8 kHz.
Measures of cochlear selectivity can be obtained from compound responses using tone-on-tone masking procedures [Dallos and Cheatham, J. Acoust. Soc. Am. 59, 591--597 (1976)]. For the normal guinea pig, cochlear fiber tuning is sharper by a factor of 1.8 than AP tuning curves using simultaneous masking (threshold criterion = 25% N1 amplitude reduction). Anesthesia does not appear to affect AP tuning. In pathological cochleas, AP tuning is broadened by a factor of 2--3, and differences between forward and simultaneous masking curves are reduced. Tuning changes can sometimes occur without threshold elevation. AP tuning curves were obtained from humans during transtympanic electrocochleography. For subjects with near normal thresholds, Q10dB values (simultaneous masking) are approximately 2.3 at 2 kHz, 3.6 at 4 kHz, and 4.7 at 8 kHz. Using the relationship between cochlear fiber tuning and AP tuning in the guinea pig, estimates of human cochlear fiber tuning are 4.2 at 2 kHz, 6.5 at 4 kHz, and 8.5 at 8 kHz. Patients with threshold elevations of more than 30 dB resulting from cochlear deafness have AP tuning curves less sharply tuned by a factor of 2--3.
Cochlear fiber discharge rate-versus-intensity functions, across frequency, have been measured in pathological guinea pig cochleas (ototoxic antibiotic poisoning) and compared with the normal animal. The frequency dependence of the slopes of these functions is reduced in cochlear pathology which results in minimum threshold elevations of more than 50 dB, i.e., there is a reduction in this frequency dependent nonlinearity. The rate functions at characteristic frequency (CF) become abnormally steep (e.g., 4--5 spikes/s/dB compared with a normal 1--2 spikes/s/dB), and comparable to those of the low-frequency tail region of normal cochlear fibers. The CF dynamic range is reduced from 30--40 to 10--15 dB in cochlear pathology. The fiber study has been confirmed by (and has confirmed) a method of indirect measurement of rate functions from AP suppression-versus-intensity functions using a pure-tone forward masking paradigm [Abbas and Gorga, J. Acoust. Soc. Am. 69, 492--499 (1981)]. This method has been used in normal and pathological guinea pigs, and the results parallel the single fiber study. In addition, AP suppression functions, across frequency, have been obtained in human subjects with (near) normal hearing thresholds, and in patients with sensorineural hearing loss of cochlear origin, during transtympanic electrocochleography. The AP suppression curves in pathology indicate, as for the animal studies, a loss of the frequency dependency of the rate function slopes, and predict steep rate functions at CF (and thus reduced dynamic range) in cochlear deafness. The findings are related to loudness recruitment.
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Some temporal coding properties of cochlear nerve fibers are investigated in kanamycin-treated guinea pigs (GPs) with various degrees of outer hair cell (OHC) degeneration. In particular, the phase locking ability of fibres from pathological cochleas, and also their adaptation properties are compared with the properties of normal cochlear fibres. No systematic effects of OHC loss on these properties have so far been found. These preliminary results therefore suggest (in so far as these animals can be regarded as models of sensorineural hearing loss of cochlear origin in man) that little deterioration should be expected in functions purely dependent upon faithful temporal coding of the stimulus waveform.
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A survey interview and the structured Type A interview (SI) were administered to 903 residents of Washtenaw County, Michigan aged 18 or older selected by a multistage probability sample of households. No bivariate relationship was found between Type A behavior and sex or marital status. Type A behavior was positively related to income and education. The prevalence of Type A behavior was highest among those who were employed in white-collar occupations. There was an inverted U-shaped relationship between age and Type A behavior. A slightly higher prevalence of Type A behavior was noted among whites than among nonwhites. Multivariate analysis showed the seven demographic variables to account for 6.8% of the overall variation in Type A behavior, with family income being the strongest demographic predictor.
Structured interview (SI) assessments of global and component Type A behavior were conducted in a general population sample of 903 respondents. Correlations among all the measures were positive and significant. A factor analysis revealed that the common component variance was explained by a single underlying factor. Interrater reliabilities were approximately 0.5 to 0.7 for the individual components and 0.8 for both the SI global Type A and a second global measure that was assigned independently by assessors who did the component scoring. Prediction of the SI-assessed global measure from the components accounted for 56% of the variance, and prediction of the second global measure from the components accounted for about 83% of the variance. Implications of the psychometric properties of the SI component and global measures of Type A behavior for future research are discussed.
We have assessed sound frequency and intensity responses in primary auditory cortex of the (ketamine) anesthetized chinchilla using optical imaging of intrinsic signals. Temporal cortex was exposed via a 10-mm craniotomy and a windowed chamber was mounted. A 4-second period of gated tones (10 ms rise/fall; 50 ms plateau; 10/s) was presented to the contralateral ear at levels between 0 and 80 dB SPL. The cortical surface was illuminated with 540 nm light and video images captured in 0.5-second bins for 7.5 s (Imager 2001; Optical Imaging). Intrinsic signals were first apparent 0.5-1 s after stimulus onset, and were maximal after 3-4 s; they decayed over several seconds. The cortical area in which intrinsic activity was detected corresponded closely with electrophysiologically defined AI cortex. Intrinsic signals can reliably be detected to stimuli at 30-40 dB SPL, and in general, the area of intrinsic signal activity tends to expand with increasing stimulation level. Using stimulation levels of 80 dB SPL, we show that low-frequency stimuli (0.5-1 kHz) evoke intrinsic signals in anterior areas whilst posterior areas are activated by high-frequency stimuli (e.g. 16 kHz). Thus a low- to high-frequency tonotopic organization is seen along this axis.
The anticancer drug carboplatin has been used to generate inner hair cell (IHC) lesions in the cochlea of chinchillas. This has provided a valuable model for the study of the relative roles of IHCs and outer hair cells (OHCs). In the present study, we examined the pathological and temporal relationships between the degeneration of the cochlear IHCs and type I spiral ganglion cells (SGCs). A single intravenous dose of 200 mg/m2 carboplatin produced extensive IHC loss with no apparent effect on the OHCs. The auditory brainstem response threshold was significantly elevated by 2 weeks following treatment and remained stable through 12 weeks. Elevated thresholds were well correlated with morphological lesions. On the other hand, the SGC population progressively decreased from 2 to 12 weeks after treatment, to about half of the control density values. A positive correlation existed between the density of SGC and the number of surviving IHCs. These results indicate that selective damage to IHCs causes a distinct loss of SGCs.
We have measured the changes in transient otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) during and after ototoxic amikacin treatment in an animal (chinchilla) model. TEOAE and DPOAE were recorded from 6 adult chinchillas over a 6-week time course starting just before a 5-day or 7-day treatment period with amikacin sulphate (400 mg/kg/day, i.m.). After final recordings, cochlear morphology was assessed by scanning electron microscopy. Generally, both DPOAE and TEOAE amplitudes change during and after treatment in a systematic fashion. High-frequency components change first, followed by lower-frequency components. We note that there is often a long latency to the onset of changes in otoacoustic emissions (OAE), and that these changes can continue for weeks after treatment. Most importantly we report that when the basal region of the cochlea is damaged in the frequency region above the OAE recording bandwidth (0.6-6 kHz for TEOAE; 1-6.7 kHz for DPOAE), we often find an increase in OAE amplitudes. More specifically, we note that as a cochlear lesion progresses apically, there is often a transient increase in a frequency-specific OAE before it reduces or is lost. Our results suggest that the increase in OAE amplitudes precedes the expression of detectable cochlear pathology.
One of the basic functions of the cochlea is to separate out the frequency components which are present in complex sounds. This frequency selectivity can be measured objectively in the clinic from the compound action potential (AP) during transtympanic electrocochleography, using a two-tone masking paradigm. An AP is evoked by a test tone near to threshold, and a measure is made of the frequency bandwidth over which this AP can be suppressed by a continuous pure tone masker. In normal-hearing subjects, this frequency range is 0.17-0.39 octaves (test tone pip at 4 or 8 kHz). In patients with cochlear deafness, this bandwidth is greatly enlarged, ranging from 0.42-2.2 octaves. Some observations suggest that a deterioration in frequency selectivity can occur before any important threshold elevation. The early detection of this could be a warning sign of potential cochlear susceptibility. In the clinic the measure is already of use: a deterioration is a positive indication of cochlear involvement in a hearing loss.
Deferoxamine mesylate (DF) is a chelating agent used for the treatment of iron overload. Recently audiological testing of patients on long-term treatment with this drug indicated the possibility of an ototoxic side effect (1). We administered DF to chinchillas with both acute and chronic regimes. Functional and histological damage to the cochlea was detected only in the acute experiment. This was assumed to come not from the direct effect of DF on the cochlea but from the hypoxia as a result of respiratory suppression due to DF toxicity. To confirm this, animals were exposed to hypoxia during the same time course as for the DF experiment. Histological and physiological consequences of this hypoxia alone revealed very similar results to that observed in the acute DF experiment. This implies that DF has little direct toxic effect on the cochlea and, more importantly that considerable attention to hypoxia should be paid when assessing the cochlear pathology of animals which have been subjected to general anesthesia for long periods.
We have found a reorganization of tonotopic maps (based on neuron response thresholds) in primary auditory cortex of the adult chinchilla after amikacin-induced basal cochlear lesions. We find an over-representation of a frequency that corresponds to the border area of the cochlear lesion. The reorganization observed is similar in extent to that previously seen in a developmental model. The properties of neurons within the over-represented area were investigated in order to determine whether their responses originated from a common input (an indication of true plasticity) or represented only the result of truncating the activity of the sensory epithelium ("pseudo-plasticity"). Some aspects of our data fit with a true plasticity model and indicate the potential for the deafferented cortex of the mature cortex to regain connections with the surviving sensory epithelium.
This paper is based on a review lecture presented at the Scientific Workshop on Evoked Potentials at Brugmann University Hospital, Brussels, Belgium on 25 February, 1984. The first part briefly reviews electrophysiological studies in experimental animals which reveal in detail the changes in cochlear function which results from various types of cochlear damage. The experimental animals represent animal models of certain types of sensorineural hearing loss of cochlear origin in man. Particular attention is given to measures of cochlear frequency selectivity and the deterioration which results from cochlear pathology. The second part deals with objective electrophysiological measures of cochlear frequency selectivity (tone on tone suppression curves) in patients with cochlear hearing loss of various etiology. These measures are mainly derived using transtympanic electrocochleography (AP tuning curves); preliminary studies of auditory brainstem response (ABR) P5 tuning curves are also described. Protocols and the rationale for such measures in the clinic are discussed.