Cynthia G. Fowler

An individualized, sensitive frequency range for early detection of ototoxicity

OBJECTIVE The aim of this study was to identify auditory frequencies at which serial threshold testing would provide the greatest sensitivity for early detection of ototoxicity. The overall objective is to develop a more time-efficient ototoxicity monitoring protocol. DESIGN Threshold data were analyzed from 370 hospitalized patients treated with aminoglycoside antibiotics (AMGs) or cisplatin (CDDP) who received serial auditory monitoring before, during, and after treatment at conventional (0.25 to 8 kHz) and high (9 to 20 kHz) frequencies. RESULTS For patients showing hearing changes due to ototoxicity, a frequency range was identified for its apparent high sensitivity to initial ototoxicity. This sensitive range is identified according to an individuals hearing threshold configuration, and is, therefore, unique for each patient. The range consists of five frequencies, generally separated by 1/6 octave, e.g., 8, 9, 10, 11.2, and 12.5 kHz. To determine frequencies and combinations of frequencies that were most often involved in ototoxicity detection, threshold data in the sensitive range were analyzed in detail. This analysis suggests that patients receiving treatment with AMG or CDDP can be monitored for hearing thresholds at only five frequencies, resulting in an 84% detection rate for AMG and 94% for CDDP compared with monitoring at all conventional and high frequencies. CONCLUSIONS This comprehensive analysis supports earlier observations that a sensitive, limited frequency range exists in which serial threshold monitoring will provide early warning of ototoxicity before effects in the speech frequency range. This finding is now being evaluated in a prospective investigation.

High-frequency audiometric monitoring strategies for early detection of ototoxicity

Therapeutic drugs such as the aminoglycoside antibiotics (AMG) and the chemotherapy agent cisplatin (CDDP) are known to cause irreversible hearing loss, typically affecting highest frequency hearing first with progression of loss to the lower frequency regions. Conventional (0.25-8 kHz) and high-frequency (9-20 kHz) serial hearing threshold monitoring was done in 123 hospitalized patients (222 ears) administered AMG or CDDP. Of ears showing a decrease in sensitivity corresponding with treatment, 62.5% demonstrated initial hearing loss solely in the high-frequency range, 13.5% first showed loss only in the conventional-frequency range, and 24.0% showed loss in both frequency ranges concurrently. Thus, if only high frequencies had been monitored, early change in auditory sensitivity would have been detected in 86.5% of these patients. Further analysis revealed a range of five frequencies, specific to each individuals hearing threshold configuration, in which initial ototoxicity appeared most likely to be detected. Testing only these five frequencies would have identified 89.2% of ears that showed change. The results of this study confirm the need to serially monitor auditory thresholds, especially in the high-frequency range, of patients receiving ototoxic drugs. A shortened five-frequency monitoring protocol is presented and suggested for use with patients unable to tolerate lengthy audiometric testing procedures.

Age-related changes in auditory function of rhesus monkeys (Macaca mulatta).

The purpose of this study was to investigate the changes in auditory function associated with aging in rhesus monkeys (Macaca mulatta) as a model for age-related changes in humans. One advantage of using monkeys from the Wisconsin Regional Primate Research Center was that lifestyle factors such as diet and excessive noise exposure were controlled. Twenty younger (mean: 10 years, 9 months, S.D.=+/-6 months) and 20 older (mean: 25 years, 11 months, S.D.=+/-11 months) monkeys were used in this study. Cochlear function in these monkeys was measured with distortion product otoacoustic emissions (DPOAEs); neural function was measured with auditory brainstem responses (ABRs) and middle latency responses (MLRs). Older monkeys had (1) significantly smaller DPOAEs, (2) significantly smaller ABR peak amplitudes, and (3) significantly longer ABR peak latencies compared to younger monkeys. Overall, these results suggest that older monkeys have decreased cochlear and neural function to the level of the brainstem as compared to younger monkeys. The decrease in DPOAE level and the increase in age accounted for approximately 70% of the increase in peak IV latency.

Tuning curves of cochlear and brainstem responses in the guinea pig.

A tone-on-tone masking paradigm was used to determine tuning curves of cochlear and brainstem responses in the guinea pig. The tuning curves are considered to be a measure of the frequency specificity of these potentials. Calculated Q10 values are used in an indicator of the sharpness of tuning of these potentials. The tuning curves of cochlear and brainstem responses were found to be similar with both showing considerable frequency specificity.

Assessment of auditory function in rhesus monkeys (Macaca mulatta): effects of age and calorie restriction

Age-related alterations in auditory function were evaluated in adult male rhesus monkeys (Macaca mulatta) involved in a long-term study evaluating the effects of caloric restriction (CR) on aging. We assessed 26 monkeys in a control group fed a low fat, high fiber diet at approximately ad libitum levels and 24 monkeys in a CR group that were fed the same diet reduced in amount by 30% compared to age- and weight-matched controls. The following measures of auditory function were obtained while monkeys were maintained under anesthesia: (1) distortion product otoacoustic emissions (DPOAEs); (2) auditory brainstem responses (ABRs); and (3) middle latency responses (MLRs). All DPOAE measures and peak II amplitude significantly decreased with age, while peak IV latency and ABR threshold significantly increased with age. We found no significant effects of CR on any auditory parameters examined.

Effect of stimulus level and frequency on ABR and MLR binaural interaction in human neonates

Auditory brainstem (ABR) and middle latency (MLR) responses were evoked by click and tone-burst stimuli from human neonates. Electrophysiologic evidence of binaural interaction was measured by subtracting waveforms obtained for binaural stimulus conditions from waveforms obtained for the sum of right ear monaural and left ear monaural stimulus conditions. The effects of stimulus level and stimulus frequency on binaural interaction were evaluated by measuring the number, latency and amplitude of components found in the derived binaural interaction waveform, that is, binaural interaction components (BIC). BICs were more prevalent in the latency range of ABRs than for MLRs. Click and tonal stimuli were equally effective for deriving ABR-BICs, while tone-bursts were somewhat less effective than clicks for deriving MLR-BICs. Stimulus-response dependencies for ABR and MLR component latencies were apparent in monaural, binaural and binaural interaction waveforms. Normalized amplitudes for BICs showed that low-frequency tone-burst stimuli resulted in the largest values compared to click and high-frequency tonal stimuli. Comparison of these results with published results from adults demonstrated immaturity of binaural interaction in neonates.

Auditory function in rhesus monkeys: Effects of aging and caloric restriction in the Wisconsin monkeys five years later

Caloric restriction (CR) slows aging in many species and protects some animals from age-related hearing loss (ARHL), but the effect on humans is not yet known. Because rhesus monkeys are long-lived primates that are phylogenically closer to humans than other research animals are, they provide a better model for studying the effects of CR in aging and ARHL. Subjects were from the pool of 55 rhesus monkeys aged 15-28 years who had been in the Wisconsin study on CR and aging for 8-13.5 years. Distortion product otoacoustic emissions (DPOAE) with f2 frequencies from 2211 to 8837 Hz and auditory brainstem response (ABR) thresholds from clicks and 8, 16, and 32 kHz tone bursts were obtained. DPOAE levels declined linearly at approximately 1 dB/year, but that rate doubled for the highest frequencies in the oldest monkeys. There were no interactions for diet condition or sex. ABR thresholds to clicks and tone bursts showed increases with aging. Borderline significance was shown for diet in the thresholds at 8 kHz stimuli, with monkeys on caloric restriction having lower thresholds. Because the rhesus monkeys have a maximum longevity of 40 years, the full benefits of CR may not yet be realized.

Low-frequency activity in the binaural interaction component of the auditory brain stem response.

The purpose of this study were to determine (1) the contribution of low-frequency activity in the auditory brain stem response (ABR) to the binaural interaction component, and (2) an optimal set of parameters for recording the binaural interaction component. ABRs were recorded from 12 adult subjects with normal hearing using 1000 Hz tone pips at three stimulation rates (10, 25, and 50/sec) and two physiological filters (150-3000 and 30-3000 Hz). The latencies of wave V in the sum of the left and right monaural responses [V(L + R)] were shorter with the 150 to 3000 Hz filter than with the 30 to 3000 Hz filter, whereas the amplitudes of V(L + R) and peak A of the binaural interaction component were similar. The amplitudes of V(L + R) and A were larger for 50/sec than for 10 or 25/sec, but the amplitude ratio of peak A to wave V(L + R) was not different. In conclusion, (1) the activity between 30 to 150 Hz did not enhance the binaural interaction component, and (2) the largest and most reliable binaural interaction component was recorded with a rate of 50/sec and a filter setting of 150 to 3000 Hz.

Aging and Middle Ear Function in Rhesus Monkeys (Macaca mulatta): Envejecimiento y funcion del oido medio en monos Rhesus [Macaca mulatta)

This study provided tympanometric data on rhesus monkeys (Macaca mulatta) and more support for this monkey as a good model for human peripheral auditory function. There have been few published reports concerning middle ear function in rhesus monkeys, and these experiments addressed that need. In the first experiment, peak acoustic admittance (Ytm) and ear-canal volume (Vea) were measured in 17 older adult monkeys and 16 younger adult monkeys. In the second experiment, middle ear resonance frequency was measured in eight younger adult monkeys and four older adult monkeys. Overall, peak Ytm, Vea and resonance frequency were similar for monkeys and humans. Specifically, peak mean Ytm and mean Vea in monkeys were comparable to those values in human children. There was a trend for older monkeys to have decreased peak Ytm and Vea, but these trends did not reach statistical significance. There was a significant sex effect similar to what has been reported in humans. Male monkeys had larger peak Ytm values and larger Vea values compared with female monkeys regardless of age. Finally, there were no significant age or sex effects on resonance frequency. Sumario En este estudio se obtuvieron datos timpanométricos de monos rhesus (Macaca mulatta) y más evidencias de que este mono es un buen modelo para estudiar la audición periférica del humano. Hay pocas publica-ciones acerca de la función del oído medio de los monos rhesus y aquí demostramos la necesidad de tales estudios. En el primer experimento se midió la admitancia acústica pico (Ytm) y el volumen del conducto auditivo (Vea) en 17 monos adultos may-ores y 16 monos adultos jóvenes. En el segundo experimento se midió la frecuencia de resonancia del oído medio en 8 adultos jóvenes y 4 adultos mayores. Las tres mediciones resultaron similares a las del humano. Específicamente las cifras pico promedio de Ytm y promedio de Vea en monos fueron compara-bles a las del nino. Hay cierta tendencia a tener cifras menores de Ytm y Vea en los monos mayores, pero esta tendencia no es estadísticamente significa-tiva. Sí existe una diferencia significativa en cuanto a genero, tal como se ha reportado en el humano. Los monos humanos tienen valores mayores de Ytm y de Vea en comparacion con los monos hembras, sin importar la edad. Finalmente, no hubo diferencia significativa en la frecuencia de resonancia entre los grupos etáreos o de género.

Graduate Education in Audiology: We Agree With the Diagnosis, But Not the Treatment.

ate program. This would leave 2 years of master’s work for truly advanced education and clinical work. This structure could parallel that in speech-language pathology; undergraduate audiology majors would receive two surveytype courses in speech-language pathology, just as current speech-language pathology majors receive such coursework in audiology. The focus, however, would be on audiology and hearing science as an undergraduate, especially during the final 2 years. Six years of college education should be more than adequate to enable students to achieve the highest level of competence as audiologists, as long as a significant amount of the educational process was allowed to take place during the first 2 years. The American Speech-Language-Hearing Association (ASHA) has recently recognized that speech-language pathology and audiology are two separate professions, with professional responsibilities and educational needs unique to each profession. Having recognized this, it then seems only logical to develop equivalent and parallel educational guidelines for each profession. An undergraduate major in audiology and hearing sciences with a 2-year master’s program in audiology would parallel the existing educational model in speech-language pathology and would greatly improve the quality of education in audiology. To better illustrate these concepts, in Table 1 we describe in detail a model 6-year audiology curriculum currently under consideration at Indiana University. This curriculum is just one of many possible ways in which the education of audiologists can be improved within the existing bachelor’s/master’s framework. It is included here as only one specific example of how the general principles discussed above can be realized within an existing bachelor’s/ master’s educational framework. As seen in this table, the first 2 to 2.5 years of this curriculum are devoted to acquiring a broad base in the fundamentals: math, science, computer sciences, psychology, etc. As the student progresses through the curriculum, the content becomes more specialized and clinically oriented and the amount and diversity of clinical practicum also increases. In this particular model, on completion of the master’s Graduate Education in Audiology: We Agree With the Diagnosis, But Not the Treatment