Shawn S. Goodman

High-frequency click-evoked otoacoustic emissions and behavioral thresholds in humans

Relationships between click-evoked otoacoustic emissions (CEOAEs) and behavioral thresholds have not been explored above 5 kHz due to limitations in CEOAE measurement procedures. New techniques were used to measure behavioral thresholds and CEOAEs up to 16 kHz. A long cylindrical tube of 8 mm diameter, serving as a reflectionless termination, was used to calibrate audiometric stimuli and design a wideband CEOAE stimulus. A second click was presented 15 dB above a probe click level that varied over a 44 dB range, and a nonlinear residual procedure extracted a CEOAE from these click responses. In some subjects (age 14-29 years) with normal hearing up to 8 kHz, CEOAE spectral energy and latency were measured up to 16 kHz. Audiometric thresholds were measured using an adaptive yes-no procedure. Comparison of CEOAE and behavioral thresholds suggested a clinical potential of using CEOAEs to screen for high-frequency hearing loss. CEOAE latencies determined from the peak of averaged, filtered temporal envelopes decreased to 1 ms with increasing frequency up to 16 kHz. Individual CEOAE envelopes included both compressively growing longer-delay components consistent with a coherent-reflection source and linearly or expansively growing shorter-delay components consistent with a distortion source. Envelope delays of both components were approximately invariant with level.

The origin of SFOAE microstructure in the guinea pig

Human stimulus-frequency otoacoustic emissions (SFOAEs) evoked by low-level stimuli have previously been shown to have properties consistent with such emissions arising from a linear place-fixed reflection mechanism with SFOAE microstructure thought to be due to a variation in the effective reflectance with position along the cochlea [Zweig and Shera, J. Acoust. Soc. Am. 98 (1995) 2018-2047]. Here we report SFOAEs in the guinea pig obtained using a nonlinear extraction paradigm from the ear-canal recording that show amplitude and phase microstructure akin to that seen in human SFOAEs. Inverse Fourier analysis of the SFOAE spectrum indicates that SFOAEs in the guinea pig are a stimulus level-dependent mix of OAEs arising from linear-reflection and nonlinear-distortion mechanisms. Although the SFOAEs are dominated by OAE generated by a linear-reflection mechanism at low and moderate stimulus levels, nonlinear distortion can dominate some part of, or all of, the emission spectrum at high levels. Amplitude and phase microstructure in the guinea pig SFOAE is evidently a construct of (i). the complex addition of nonlinear-distortion and linear-reflection components; (ii). variation in the effective reflectance with position along the cochlea; and perhaps (iii). the complex addition of multiple intra-cochlear reflections.

Detecting high-frequency hearing loss with click-evoked otoacoustic emissions

In contrast to clinical click-evoked otoacoustic emission (CEOAE) tests that are inaccurate above 4-5 kHz, a research procedure measured CEOAEs up to 16 kHz in 446 ears and predicted the presence/absence of a sensorineural hearing loss. The behavioral threshold test that served as a reference to evaluate CEOAE test accuracy used a yes-no task in a maximum-likelihood adaptive procedure. This test was highly efficient between 0.5 and 12.7 kHz: Thresholds measured in 2 min per frequency had a median standard deviation (SD) of 1.2-1.5 dB across subjects. CEOAE test performance was assessed by the area under the receiver operating characteristic curve (AUC). The mean AUC from 1 to 10 kHz was 0.90 (SD=0.016). AUC decreased to 0.86 at 12.7 kHz and to 0.7 at 0.5 and 16 kHz, possibly due in part to insufficient stimulus levels. Between 1 and 12.7 kHz, the medians of the magnitude difference in CEOAEs and in behavioral thresholds were <4 dB. The improved CEOAE test performance above 4-5 kHz was due to retaining the portion of the CEOAE response with latencies as short as 0.3 ms. Results have potential clinical significance in predicting hearing status from at least 1 to 10 kHz using a single CEOAE response.

Further assessment of forward pressure level for in situ calibration.

Quantifying ear-canal sound level in forward pressure has been suggested as a more accurate and practical alternative to sound pressure level (SPL) calibrations used in clinical settings. The mathematical isolation of forward (and reverse) pressure requires defining the Thévenin-equivalent impedance and pressure of the sound source and characteristic impedance of the load; however, the extent to which inaccuracies in characterizing the source and/or load impact forward pressure level (FPL) calibrations has not been specifically evaluated. This study examined how commercially available probe tips and estimates of characteristic impedance impact the calculation of forward and reverse pressure in a number of test cavities with dimensions chosen to reflect human ear-canal dimensions. Results demonstrate that FPL calibration, which has already been shown to be more accurate than in situ SPL calibration, can be improved particularly around standing-wave null frequencies by refining estimates of characteristic impedance. Better estimates allow FPL to be accurately calculated at least through 10 kHz using a variety of probe tips in test cavities of different sizes, suggesting that FPL calibration can be performed in ear canals of all sizes. Additionally, FPL calibration appears a reasonable option when quantifying the levels of extended high-frequency (10-18 kHz) stimuli.

Delays and Growth Rates of Multiple TEOAE Components

Bandpass‐filtered transient‐evoked otoacoustic emissions (TEOAEs) show multiple energy peaks with time delays that are invariant with level and growth rates that vary with delay and stimulus level, suggesting that multiple generation mechanisms may be involved at moderate and high stimulus levels. We measured delays and magnitude growths of multiple TEOAE energy peaks and compared the results obtained from linear and nonlinear extraction methods. To test the hypothesis that early components are generated at the basal portion of the cochlea, delays and growth rates were also measured in the presence of highpass masking noise for a subset of subjects. No effect of the highpass masking was seen. The results are discussed in terms of potential generation mechanisms of the multiple energy peaks.

RNA Interference Prevents Autosomal-Dominant Hearing Loss

Hearing impairment is the most common sensory deficit. It is frequently caused by the expression of an allele carrying a single dominant missense mutation. Herein, we show that a single intracochlear injection of an artificial microRNA carried in a viral vector can slow progression of hearing loss for up to 35 weeks in the Beethoven mouse, a murine model of non-syndromic human deafness caused by a dominant gain-of-function mutation in Tmc1 (transmembrane channel-like 1). This outcome is noteworthy because it demonstrates the feasibility of RNA-interference-mediated suppression of an endogenous deafness-causing allele to slow progression of hearing loss. Given that most autosomal-dominant non-syndromic hearing loss in humans is caused by this mechanism of action, microRNA-based therapeutics might be broadly applicable as a therapy for this type of deafness.

Short-latency transient-evoked otoacoustic emissions as predictors of hearing status and thresholds.

Estimating audiometric thresholds using objective measures can be clinically useful when reliable behavioral information cannot be obtained. Transient-evoked otoacoustic emissions (TEOAEs) are effective for determining hearing status (normal hearing vs hearing loss), but previous studies have found them less useful for predicting audiometric thresholds. Recent work has demonstrated the presence of short-latency TEOAE components in normal-hearing ears, which have typically been eliminated from the analyses used in previous studies. The current study investigated the ability of short-latency components to predict hearing status and thresholds from 1-4 kHz. TEOAEs were measured in 77 adult ears with thresholds ranging from normal hearing to moderate sensorineural hearing loss. Emissions were bandpass filtered at center frequencies from 1 to 4 kHz. TEOAE waveforms were analyzed within two time windows that contained either short- or long-latency components. Waveforms were quantified by root-mean-square amplitude. Long-latency components were better overall predictors of hearing status and thresholds, relative to short-latency components. There were no significant improvements in predictions when short-latency components were included with long-latency components in multivariate analyses. The results showed that short-latency TEOAE components, as analyzed in the current study, were less predictive of both hearing status and thresholds from 1-4 kHz than long-latency components.

Within- and Across-Subject Variability of Repeated Measurements of Medial Olivocochlear-Induced Changes in Transient-Evoked Otoacoustic Emissions.

Objectives: Measurement of changes in transient-evoked otoacoustic emissions (TEOAEs) caused by activation of the medial olivocochlear reflex (MOCR) may have clinical applications, but the clinical utility is dependent in part on the amount of variability across repeated measurements. The purpose of this study was to investigate the within- and across-subject variability of these measurements in a research setting as a step toward determining the potential clinical feasibility of TEOAE-based MOCR measurements. Design: In 24 normal-hearing young adults, TEOAEs were elicited with 35 dB SL clicks and the MOCR was activated by 35 dB SL broadband noise presented contralaterally. Across a 5-week span, changes in both TEOAE amplitude and phase evoked by MOCR activation (MOC shifts) were measured at four sessions, each consisting of four independent measurements. Efforts were undertaken to reduce the effect of potential confounds, including slow drifts in TEOAE amplitude across time, activation of the middle-ear muscle reflex, and changes in subjects’ attentional states. MOC shifts were analyzed in seven 1/6-octave bands from 1 to 2 kHz. The variability of MOC shifts was analyzed at the frequency band yielding the largest and most stable MOC shift at the first session. Within-subject variability was quantified by the size of the standard deviations across all 16 measurements. Across-subject variability was quantified as the range of MOC shift values across subjects and was also described qualitatively through visual analyses of the data. Results: A large majority of MOC shifts in subjects were statistically significant. Most subjects showed stable MOC shifts across time, as evidenced by small standard deviations and by visual clustering of their data. However, some subjects showed within- and across-session variability that could not be explained by changes in hearing status, middle ear status, or attentional state. Simulations indicated that four baseline measurements were sufficient to predict the expected variability of subsequent measurements. However, the measured variability of subsequent MOC shifts in subjects was often larger than expected (based on the variability present at baseline), indicating the presence of additional variability at subsequent sessions. Conclusions: Results indicated that a wide range of within- and across-subject variability of MOC shifts was present in a group of young normal-hearing individuals. In some cases, very large changes in MOC shifts (e.g., 1.5 to 2 dB) would need to occur before one could attribute the change to either an intervention or pathology, rather than to measurement variability. It appears that MOC shifts, as analyzed in the present study, may be too variable for clinical use, at least in some individuals. Further study is needed to determine the extent to which changes in MOC shifts can be reliably measured across time for clinical purposes.

Basal contributions to short-latency transient-evoked otoacoustic emission components.

The presence of short-latency (SL), less compressive-growing components in bandpass-filtered transient-evoked otoacoustic emission (TEOAE) waveforms may implicate contributions from cochlear regions basal to the tonotopic place. Recent empirical work suggests a region of SL generation between ∼1/5 and 1/10-octave basal to the TEOAE frequency’s tonotopic place. However, this estimate may be biased to regions closer to the tonotopic place as the TEOAE extraction technique precluded measurement of components with latencies shorter than ∼5 ms. Using a variant of the non-linear, double-evoked extraction paradigm that permitted extraction of components with latencies as early as 1 ms, the current study empirically estimated the spatial-extent of the cochlear region contributing to 2 kHz SL TEOAE components. TEOAEs were evoked during simultaneous presentation of a suppressor stimulus, in order to suppress contributions to the TEOAE from different places along the cochlear partition. Three or four different-latency components of similar frequency content (∼2 kHz) were identified for most subjects. Component latencies ranged from 1.4 to 9.6 ms; latency was predictive of the component’s growth rate and the suppressor frequency to which the component’s magnitude was most sensitive to change. As component latency decreased, growth became less compressive and suppressor-frequency sensitivity shifted to higher frequencies. The shortest-latency components were most sensitive to suppressors approximately 3/5-octave higher than their nominal frequency of 2 kHz. These results are consistent with a distributed region of generation extending to approximately 3/5-octave basal to the TEOAE frequency’s tonotopic place. The empirical estimates of TEOAE generation are similar to model-based estimates where generation of the different-latency components occurs through linear reflection from impedance discontinuities distributed across the cochlear partition.

Measurement of hearing aid internal noise

Hearing aid equivalent input noise (EIN) measures assume the primary source of internal noise to be located prior to amplification and to be constant regardless of input level. EIN will underestimate internal noise in the case that noise is generated following amplification. The present study investigated the internal noise levels of six hearing aids (HAs). Concurrent with HA processing of a speech-like stimulus with both adaptive features (acoustic feedback cancellation, digital noise reduction, microphone directionality) enabled and disabled, internal noise was quantified for various stimulus levels as the variance across repeated trials. Changes in noise level as a function of stimulus level demonstrated that (1) generation of internal noise is not isolated to the microphone, (2) noise may be dependent on input level, and (3) certain adaptive features may contribute to internal noise. Quantifying internal noise as the variance of the output measures allows for noise to be measured under real-world processing conditions, accounts for all sources of noise, and is predictive of internal noise audibility.