Shaum P. Bhagat

Modification of otoacoustic emissions following ear-level exposure to MP3 player music.

The purpose of this study was to examine if a pre-determined exposure level and duration of MP3 player music would result in significant changes in cochlear function when measured with audiometric and physiological methods. Distortion-product otoacoustic emissions (DPOAEs), synchronized spontaneous otoacoustic emissions (SSOAEs), and hearing thresholds were measured in 20 normal-hearing adults before and after a 30-minute MP3 player music exposure. DPOAEs were acquired with 65/45 dB SPL primary tones (f2=0.842–7.996 kHz) with a frequency resolution of 8 points/octave. A probe microphone system recorded ear-canal music levels and was used to equalize levels at approximately 85 dBC across individuals during the music presentation. Comparison of pre- and post-exposure measurements revealed no significant differences in hearing thresholds, but DPOAE levels in half-octave bands centered from 1.4–6.0 kHz were significantly reduced following the music exposure. Post-exposure shifts in SSOAE frequency and level were highly variable in individuals identified with SSOAEs. The results for the exposure conditions explored in this study indicate that changes in otoacoustic emissions may precede the development of music-induced hearing threshold shifts.

Right-ear advantage drives the link between olivocochlear efferent 'antimasking' and speech-in-noise listening benefits.

The mammalian cochlea receives feedback from the brainstem medial olivocochlear (MOC) efferents, whose putative ‘antimasking’ function is to adjust cochlear amplification and enhance peripheral signal detection in adverse listening environments. Human studies have been inconsistent in demonstrating a clear connection between this corticofugal system and behavioral speech-in-noise (SIN) listening skills. To elucidate the role of brainstem efferent activity in SIN perception, we measured ear-specific contralateral suppression of transient-evoked otoacoustic emissions (OAEs), a proxy measure of MOC activation linked to auditory learning in noisy environments. We show that suppression of cochlear emissions is stronger with a more basal cochlear bias in the right ear compared with the left ear. Moreover, a strong negative correlation was observed between behavioral SIN performance and right-ear OAE suppression magnitudes, such that lower speech reception thresholds in noise were predicted by larger amounts of MOC-related activity. This brain-behavioral relation was not observed for left ear SIN perception. The rightward bias in contralateral MOC suppression of OAEs, coupled with the stronger association between physiological and perceptual measures, is consistent with left-hemisphere cerebral dominance for speech–language processing. We posit that corticofugal feedback from the left cerebral cortex through descending MOC projections sensitizes the right cochlea to signal-in-noise detection, facilitating figure-ground contrast and improving degraded speech analysis. Our findings demonstrate that SIN listening is at least partly driven by subcortical brain mechanisms; primitive stages of cochlear processing and brainstem MOC modulation of (right) inner ear mechanics play a critical role in dictating SIN understanding.

Monitoring carboplatin ototoxicity with distortion-product otoacoustic emissions in children with retinoblastoma

OBJECTIVE Carboplatin is a common chemotherapy agent with potential ototoxic side effects that is used to treat a variety of pediatric cancers, including retinoblastoma. Retinoblastoma is a malignant tumor of the retina that is usually diagnosed in young children. Distortion-product otoacoustic emission tests offer an effective method of monitoring for ototoxicity in young children. This study was designed to compare measurements of distortion-product otoacoustic emissions obtained before and after several courses of carboplatin chemotherapy in order to examine if (a) mean distortion-product otoacoustic emission levels were significantly different; and (b) if criterion reductions in distortion-product otoacoustic emission levels were observed in individual children. METHODS A prospective repeated measures study. Ten children with a median age of 7.6 months (range, 3-72 months) diagnosed with unilateral or bilateral retinoblastoma were examined. Distortion-product otoacoustic emissions were acquired from both ears of the children with 65/55 dB SPL primary tones (f(2)=793-7996 Hz) and a frequency resolution of 3 points/octave. Distortion-product otoacoustic emission levels in dB SPL were measured before chemotherapy treatment (baseline measurement) and after 3-4 courses of chemotherapy (interim measurement). Comparisons were made between baseline and interim distortion-product otoacoustic emission levels (collapsed across ears). Evidence of ototoxicity was based on criterion reductions (≥ 6 dB) in distortion-product otoacoustic emission levels. RESULTS Significant differences between baseline and interim mean distortion-product otoacoustic emission levels were only observed at f(2) = 7996 Hz. Four children exhibited criterion reductions in distortion-product otoacoustic emission levels. CONCLUSIONS Mean distortion-product otoacoustic emission levels at most frequencies were not changed following 3-4 courses of carboplatin chemotherapy in children with retinoblastoma. However, on an individual basis, children receiving higher doses of carboplatin exhibited criterion reductions in distortion-product otoacoustic emission level at several frequencies. These findings suggest that higher doses of carboplatin affect outer hair cell function, and distortion-product otoacoustic emission tests can provide useful information when monitoring children at risk of developing carboplatin ototoxicity.

Hearing Loss in Patients Who Received Cranial Radiation Therapy for Childhood Cancer

PURPOSE Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of anticancer therapy, longitudinal reports of SNHL in childhood cancer survivors treated with contemporary RT are limited. We report the incidence, onset, severity, and long-term trajectory of SNHL among children receiving RT. Potential risk factors for SNHL were also identified. PATIENTS AND METHODS Serial audiologic testing was conducted on 235 pediatric patients who were treated with conformal or intensity-modulated RT as part of an institutional phase II trial for localized primary brain tumors, including craniopharyngioma, ependymoma, and juvenile pilocytic astrocytoma. All but one patient had measurable cochlear radiation dose (CRD) greater than 0 Gy. The median follow-up from RT initiation to latest audiogram was 9 years with a median of 11 post-RT audiograms per patient. Audiograms were classified by the Chang Ototoxicity Grading Scale. Progression was defined by an increase in Chang grade from SNHL onset to the most recent evaluation. RESULTS At last evaluation, SNHL was prevalent in 14% of patients: 2.1% had mild and 11.9% had significant SNHL requiring hearing aids. Median time from RT to SNHL onset was 3.6 years (range, 0.4 to 13.2 years). Among 29 patients with follow-up evaluations after SNHL onset, 65.5% experienced continued decline in hearing sensitivity in either ear and 34.5% had no change. Younger age at RT initiation (hazard ratio [HR], 2.32; 95% CI, 1.21 to 4.46), higher CRD (HR, 1.07; 95% CI, 1.03 to 1.11), and cerebrospinal fluid shunting (HR, 2.02; 95% CI, 1.07 to 3.78) were associated with SNHL. CONCLUSION SNHL is a late effect of RT that likely worsens over time. Long-term audiologic follow-up for a minimum of 10 years post-RT is recommended.

Efferent-induced change in human cochlear compression and its influence on masking of tones.

Several lines of evidence suggest that medial olivocochlear (MOC) efferent neurons modify cochlear output to improve signal detection in noise. In animal models, stimulation of MOC efferents reduces the amount of compression in basilar membrane (BM) growth functions. Linearization of BM growth functions may assist in extending the neural response to the signal above that of noise, leading to a decrease in masking. In order to test this hypothesis, effects of MOC efferent neurons on BM compression were studied indirectly in humans by examining the effects of contralateral noise on distortion-product otoacoustic emission (DPOAE) input-output functions at 1.0 and 2.0kHz. Compression threshold estimates from a three-segment linear regression model applied to the DPOAE functions were derived in order to determine correlations with psychophysical measurements of masking of tones at 1.0 and 2.0kHz. Contralateral noise shifted the DPOAE compression threshold to a significantly higher level at 1.0kHz, but not at 2.0kHz. A significant negative correlation between the change in DPOAE compression threshold and the amount of masking at 1.0kHz was observed, but no correlation between these variables was detected at 2.0kHz. The results of this experiment at the lower test frequency indicated that contralateral noise linearized DPOAE input-output functions, and individuals with larger DPOAE compression threshold shifts tended to exhibit less masking. Under certain conditions, decreases in cochlear compression induced by MOC efferent neurons may lead to unmasking of tones presented in noise.

Evaluation of distortion products produced by the human auditory system

During the simultaneous monaural presentation of two primary tones, distortion products can be measured acoustically in the ear canal (DPOAEs) and electrically as auditory evoked potentials (DPAEPs). The purpose of this investigation was to elucidate the sources of nonlinearity within the human auditory system responsible for generating quadratic (QDT) and cubic (CDT) difference tones. Measurements of DPOAEs and DPAEPs were obtained from 24 normal-hearing adults (12 male) in conditions with and without presentation of a 60 dB SPL contralateral noise. The effects of primary-tone signal duration and mode of presentation on measurements of DPAEPs were also examined. Results indicated that overall, both acoustic and electric distortion products were suppressed during presentation of a contralateral noise. Increases in the duration of the primary tones caused increases in DPAEP amplitudes. A greater proportion of individuals exhibited DPAEPs with monotic compared to dichotic presentation of the primary tones. The findings of the investigation supported the conjecture that a cochlear nonlinearity produced CDT acoustic and electric distortion products. Evidence concerning the origin of the QDT DPAEP was inconclusive, and contributions from both cochlear and neural nonlinear sources could not be ruled out.

Concordance between the Chang and the International Society of Pediatric Oncology (SIOP) ototoxicity grading scales in patients treated with cisplatin for medulloblastoma

Reporting ototoxicity is frequently complicated by use of various ototoxicity criteria. The International Society of Pediatric Oncology (SIOP) ototoxicity grading scale was recently proposed for standardized use in reporting hearing loss outcomes across institutions. The aim of this study was to evaluate the concordance between the Chang and SIOP ototoxicity grading scales. Differences between the two scales were identified and the implications these differences may have in the clinical setting were discussed.

Challenges in Ototoxicity Monitoring in the Pediatric Oncology Population

BACKGROUND Platinum-based chemotherapy and cranial radiation are effective treatment options commonly prescribed for a variety of childhood cancers. These therapies can, and often do, result in early- and late-onset adverse health effects such as hearing loss. Undetected hearing loss is particularly concerning in young children developing speech and language skills and can negatively affect academic achievement and the psychosocial well-being of both young and older children. Early detection of hearing loss in pediatric oncology patients and early intervention are critical to help these patients succeed in achieving these developmental milestones. PURPOSE The primary goal of this study was to create a tutorial for audiologists concerning the monitoring of ototoxicity in the pediatric oncology population. Monitoring hearing for children receiving potentially ototoxic cancer treatments presents special issues and challenges for audiologists. This tutorial will orient the reader to these special issues and challenges, and potential solutions will be proposed. DESIGN This tutorial is organized into sections, including an overview of platinum compound and cranial radiation treatments commonly used to treat pediatric cancer, modifications of the test battery required to appropriately monitor for ototoxic hearing loss in children, a proposal for a monitoring protocol, and descriptions of the grading scales that are frequently used by oncologists to determine the severity of ototoxic hearing loss. CONCLUSIONS Identification of ototoxicity is crucial in children receiving cancer treatments because of the impact that acquired hearing loss has on social and educational outcomes in the developing child. Monitoring hearing in children presents challenges that are unique to this population. Much effort has been put forth in developing and validating the International Society of Pediatric Oncology ototoxicity grading scale for international use in reporting auditory outcomes in clinical trials. In the future, the development of standardized monitoring protocols will assist audiologists in providing optimal care to children treated for cancer.

Efferent-mediated reduction in cochlear gain does not alter tuning estimates from stimulus-frequency otoacoustic emission group delays

The existence of efferent feedback from cortical and subcortical brain centers to the hair cells of the cochlea has been recognized for many years, but the role that efferent neurons play in hearing is not completely known. Stimulation of medial olivocochlear (MOC) efferent neurons suppresses sound-evoked basilar membrane responses and changes the tuning of single auditory nerve fibers in animal models. Both of these effects are linked to a MOC-induced reduction in the gain of the cochlear amplification provided by outer hair cells. To non-invasively examine the link between cochlear suppression and tuning in humans, stimulus-frequency otoacoustic emissions (SFOAEs) were recorded in conditions with and without contralateral acoustic stimulation (CAS) from 28 normal-hearing participants. SFOAEs were measured using clusters of closely-spaced probe-tone frequencies centered near 1.4 and 2.0kHz. An index of cochlear tuning, QERB, was calculated based on measures of SFOAE group delay at both 1.4 and 2.0kHz. A statistically significant (p<0.01) decrease in SFOAE levels acquired during CAS was detected only for the SFOAE cluster centered at 2kHz. No statistically significant differences in QERB were found between conditions with and without CAS at 1.4 and 2.0kHz. These findings suggest that in humans, tuning based on SFOAE group delay estimates is not appreciably altered at cochlear locations with MOC efferent-induced reductions in cochlear gain.

Time-Frequency Analysis of Transient-Evoked Otoacoustic Emissions in Children Exposed to Carboplatin Chemotherapy

The aims of this study were to characterize and quantify time-frequency changes in transient-evoked otoacoustic emissions (TEOAEs) recorded in children diagnosed with retinoblastoma who were receiving carboplatin chemotherapy. A signal processing technique, the wavelet transform (WT), was used to analyze TEOAE waveforms in narrow-band frequency components. Ten children (aged 3–72 months) diagnosed with unilateral or bilateral retinoblastoma were enrolled in the study. TEOAEs were acquired from the children with linear sequences of 70 dB peak equivalent SPL clicks. After WT analysis, TEOAE energy, latency and normalized energy in the narrow-band frequency components were compared before and during carboplatin chemotherapy treatment (average dose 1693 mg/m2). On a group basis, no significant differences (p > 0.05) in the TEOAE energy, latency or normalized energy before and after carboplatin treatment were observed. There were decreases in normalized energy on an individual basis in 10 out of 18 ears in the sample. Exposure to carboplatin chemotherapy did not cause significant changes in TEOAE energy, latency and normalized energy during treatment. However, long-term monitoring of hearing with measurements of TEOAEs is warranted, given the risks of delayed hearing loss in some children receiving carboplatin chemotherapy.