David T. Kemp

Wave and place fixed DPOAE maps of the human ear.

Human intermodulation distortion product otoacoustic emissions (DPOAE) can be a mixture of low and high latency components. They have different level, phase, and suppression characteristics, which indicate that emissions arise both from the frequency region of the primary tones directly and indirectly via the DP frequency place. Which component dominates the measured DPOAE in the ear canal depends on the stimulus parameters, especially the frequency ratio, f2/f1. Interference between the two emissions adds complexity to measurements of DPOAE. The behavior and even existence of whichever emission route is lower in level often cannot directly be deduced from the raw DPOAE data because the other emission covers it. It is therefore not known whether both emissions are present for all stimulus parameters or whether the trends seen in each emission when they are the dominant emission route continue under stimulus conditions when they are not dominant. In this study, the two DPOAE components are separated by a post-processing method. Previously, maps of raw DPOAE data against f2/f1 and DP frequency have been obtained. To separate the components, sets of data consisting of f2/f1 sweeps were transformed by an inverse Fourier transform into the time domain. The low and high latency components appeared as two distinct peaks because of their different phase gradients. These peaks were separated by windowing in the time domain and two frequency domain maps were reconstructed, representing the low and high latency DPOAEs. It was found that the low latency component of the 2 f1-f2 DP was only emitted strongly with f2/f1 between approximately 1.1 and 1.3. The removal of the high latency component revealed the low ratio edge of this region, at which the level falls sharply. However, the low latency emission has been traced at reduced amplitude over a wide range of stimulus parameters. Although previously only observed at small frequency ratios, the high latency component was found to be present widely in the lower sideband, its level reducing slowly at larger f2/f1. Its phase behavior changes in the lower sideband, being approximately constant with DP frequency at small ratios of f2/f1, but deviating from this at wider ratios. These results support the hypothesis that a DPOAE component which propagates to and is re-emitted from the DP frequency place (place fixed emission) is present across a wide parameter range. However, for all but the close primary condition the lower sideband DPOAE is dominated by direct emission from the region of f2 and f1 wave interaction (wave fixed emission). A simple transmission line model is presented to illustrate how the observed DPOAE maps can arise on the basis of this hypothesis.

The effect of noise exposure on the details of distortion product otoacoustic emissions in humans.

The effect of noise exposure on amplitude and phase of distortion product otoacoustic emissions (DPOAEs) was examined by five different paradigms: across a wideband of frequency, microstructure, input/output function, primary frequency ratio tuning curve, and group delay. The aim was to investigate the vulnerability of these different features to moderate levels of noise exposure. Nine subjects were exposed to third-octave-band noise. The DPOAE amplitude was reduced frequency specifically with the greatest reduction approximately half an octave above the frequency of the noise. The degree of amplitude reduction was greatest at low stimulus levels. There were no observed effects on the shape of the primary ratio tuning curve. A weak tendency to a decrease was seen in group delays. Distinct microstructure was seen in the amplitude against frequency of five out of seven subjects. The maximum to minimum ratio of the microstructure decreased, and the whole pattern shifted toward lower frequencies after noise exposure. Evidence of multiple internal reflection or interference was seen in the periodicity of the microstructure. Using a simple model of the microstructure based on multiple reflections, the noise-induced changes were reevaluated. A reduction in maximum to minimum microstructure ratio could be interpreted as a decrease in the internal reflection coefficient. The implications of these observations for the interpretation of the DPOAE measurements are considered.

Distortion product otoacoustic emission delay measurement in human ears

The measurement of distortion product otoacoustic emission (DPOAE) delay using the phase gradient method is discussed. A short f2 sweep paradigm is described. Its merits are discussed and comparisons made with other methods. Using sweeps of less than 4%, consistent and reliable measurements were obtained from 12 normal ears, except for a few isolated measurements. Investigation of these apparent anomalies indicated that the short f2 sweep method was sensitive to the localized effects of narrow distortion product intensity notches and spontaneous emissions. It is possible that middle ear pressure instability or some local change in the cochlea sometimes compounded the situation. The intersubject range (63% of the mean) of DPOAE delay values was greater than the range of values observed due to measurement variability (5.6% of the mean) or intrasubject variability (8.5% of the mean) demonstrating that the method can detect real differences between ears. However, comparison with previous work shows that caution is needed in interpreting these data, as all DPOAE phase methods provide only partial latency values. The physical interpretation depends on both the stimulus sweep used and the origin of DPOAES. Our data shows that f1 sweep derived latency is lower than f2 sweep data by more than 20%. Caution also needs to be exercised when comparing cochlear traveling wave delay, as inferred from electrophysiological data, with that obtained from DPOAE delay measurements.

Basic characteristics of distortion product otoacoustic emissions in infants and children

Distortion-product otoacoustic emissions at the 2 f1-f2 frequency (DPOAEs) are being advocated as a clinical tool for diagnosis of peripheral auditory pathology. Because they can be measured quickly and noninvasively, they may be an excellent method for identifying hearing loss in infants and children. However, few studies have examined the characteristics of DPOAEs in infants and children or detailed if, and how, their responses differ from those of adults. The purpose of the current study was to determine basic characteristics of DPOAEs in infants, toddlers, children, and young adults and to define any differences among age groups. An additional goal was to ensure that the presence of spontaneous otoacoustic emissions (SOAEs) did not confound any developmental effect. DPOAE input/output (I/O) functions at seven f2 frequencies and SOAEs were measured from one ear of 196 subjects. Children aged less than 1 yr had significantly higher mean DPOAE levels than older children and adults, and children aged 1-3 yr had higher mean DPOAE levels than teens and adults. These differences were dependent on frequency but were independent of f2 level and SOAE status. At every f2 frequency, groups of individuals having SOAEs had higher mean DPOAE levels than those not having SOAEs.

Multicomponent acoustic distortion product otoacoustic emission phase in humans. I. General characteristics

Phase characteristics and latency of 2f1-f2, 3f1-2f2, and 2f2-f1 acoustic distortion product otoacoustic emissions (DPOAEs) have been analyzed in 12 adults with normal hearing. Phase-versus-frequency functions (PFF) have been recorded at each of ten pairs of primary frequencies, by two methods, depending on which one of the primary frequencies f1 or f2 was swept in frequency. Whichever sweep method was used, local phase irregularities were found in the PFF and were shown to be independent of the phase variability due to the measured noise, to be reproducible and frequency specific. Phase irregularities were significantly greater in subjects exhibiting spontaneous otoacoustic emissions. The latency calculation was unaffected by phase irregularities provided that a suitably large range of f2/f1 ratio was used. The DPOAE latencies that were obtained at low ratios of primaries were significantly longer than those obtained at higher ratios. For all DPOAE components and sweep methods used, the latency decreased as frequency increased from 750 Hz to 6 kHz. Substantial intersubject differences were found. They might be due to two main factors: differences in middle ear acoustic properties and in cochlea mechanical characteristics. The influence of pressure in the outer ear canal increased the DPOAE latencies recorded with both the f1 and f2 sweep methods at low frequencies. Men showed significantly longer 2f2-f1 DPOAE latencies than women, especially at low frequencies, which can be attributed to the difference in length of the cochlea according to gender. Lastly, the latencies measured using the f2 sweep were consistently longer than the latencies obtained using an f1 sweep for lower sideband DPOAEs, but no difference was observed for upper sideband DPOAEs.

Relationships between DPOAE and TEOAE amplitude and phase characteristics

Most published data comparing the amplitudes of transient evoked otoacoustic emissions (TEOAEs) and bi-tonally evoked otoacoustic emissions (DPOAEs) indicate a low level of correlation, raising the question to what extent do the two responses share the same relationship with hearing function. However, DPOAE intensities are sensitive to stimulus parameters and comparisons with TEOAE have mostly been made with the specific range of DPOAE parameters found to optimize DP output level. To determine if other DPOAE stimulus parameter domains give closer correspondence between TEOAE and DPOAE characteristics, 2 f1−f2 and 2 f2−f1 DPOAE intensity and phase measurements were made across a sample 1/2-octave frequency range centered on 2 kHz in nine normally hearing subjects using a wide range of stimulus parameter configurations. The DP fine structure was resolved by detailed measurements and the mean DP levels were compared to those in the corresponding frequency range from TEOAE measurements obtained with the same ...

Reticular lamina and basilar membrane vibrations in living mouse cochleae

Significance The remarkable sensitivity of mammalian hearing depends on auditory sensory outer hair cells, yet how these cells enhance the hearing sensitivity remains unclear. By measuring subnanometer vibrations directly from motile outer hair cells in living inner ear, we demonstrate that outer hair cells do not directly amplify the basilar membrane vibration by local feedback as commonly expected; instead, they actively vibrate the reticular lamina over a broad frequency range. The outer hair cell-driven reticular lamina vibration interacts with the basilar membrane traveling wave through the cochlear fluid, resulting in maximal vibrations at the best-frequency location, consequently enhancing hearing sensitivity. This finding advances our knowledge of mammalian hearing and may lead to strategies for restoring hearing in patients. It is commonly believed that the exceptional sensitivity of mammalian hearing depends on outer hair cells which generate forces for amplifying sound-induced basilar membrane vibrations, yet how cellular forces amplify vibrations is poorly understood. In this study, by measuring subnanometer vibrations directly from the reticular lamina at the apical ends of outer hair cells and from the basilar membrane using a custom-built heterodyne low-coherence interferometer, we demonstrate in living mouse cochleae that the sound-induced reticular lamina vibration is substantially larger than the basilar membrane vibration not only at the best frequency but surprisingly also at low frequencies. The phase relation of reticular lamina to basilar membrane vibration changes with frequency by up to 180 degrees from ∼135 degrees at low frequencies to ∼-45 degrees at the best frequency. The magnitude and phase differences between reticular lamina and basilar membrane vibrations are absent in postmortem cochleae. These results indicate that outer hair cells do not amplify the basilar membrane vibration directly through a local feedback as commonly expected; instead, they actively vibrate the reticular lamina over a broad frequency range. The outer hair cell-driven reticular lamina vibration collaboratively interacts with the basilar membrane traveling wave primarily through the cochlear fluid, which boosts peak responses at the best-frequency location and consequently enhances hearing sensitivity and frequency selectivity.

GSSPs, global stratigraphy and correlation

Abstract Procedures used to define an international chronostratigraphic stage boundary and to locate and ratify a Global Boundary Stratotype Section and Point (GSSP) are outlined. A majority of current GSSPs use biostratigraphic data as primary markers with no reference to any physico-chemical markers, despite the International Subcommission on Stratigraphic Classification (ISSC) suggestion that such markers should be included if possible. It is argued that such definitions will not produce the high-precision Phanerozoic time scale necessary to understand such phenomena as pre-Pleistocene ice ages and global climate change. It is strongly recommended that all GSSPs should have physico-chemical markers as an integral part of their guiding criteria, and where such markers cannot be found, the GSSP should be relocated. The methods and approach embodied in oceanic stratigraphy – coring, logging, analysing and archiving of drill sites by numerous experts using a wide range of methods – could usefully serve as a scientific model for the analysis and archiving of GSSPs, all of which are on the present-day continents. The incorporation of many more stratigraphic sections into GSSP studies, the application of physico-chemical methods, and the replacement of old U–Pb dates by newer CA-TIMS U–Pb dates, together with the use of constrained optimization (CONOP) programs that produce a calendar of events from many sections, should lead to much more precise timescales for pre-Cenozoic time than are currently available.

Aminoglycoside antibiotics cochleotoxicity in paediatric cystic fibrosis (CF) patients: A study using extended high-frequency audiometry and distortion product otoacoustic emissions

Abstract Despite known ototoxic effects of aminoglycoside (AG) antibiotics, audiological assessment is not routinely undertaken in UK CF patients. Consequently, the incidence of hearing loss is not well established. Objective: To document the incidence of hearing loss in cystic fibrosis (CF) children. Design: Hearing function of 45 children from Great Ormond Street Hospital was assessed using pure-tone audiometry up to 20kHz and DPOAEs up to 8kHz. Study Sample: 39/45 of participants had received intravenous (IV) AGs, 23 of which received repeated IV AGs every 3 months. Results: In this high exposure group, 8 (21%) had clear signs of ototoxicity; average 8-20kHz thresholds were elevated by ∼50dB and DPOAE amplitudes were >10dB lower at f2 3.2-6.3 kHz. The remaining 31/39 (79%) of AG exposed patients had normal, even exceptionally good hearing. The 21% incidence of ototoxicity we observed is substantial and higher than previously reported. However, our finding of normal hearing in children with equal AG exposure strongly suggests that other unknown factors, possibly genetic susceptibility, influence this outcome. Conclusions: We recommend comparable auditory testing in all CF patients with high AG exposures. Genetic analysis may help explain the dichotomy in response to AGs found. Sumario A pesar de los conocidos efectos ototóxicos de los antibióticos aminoglucósidos (AG), en el Reino Unido no se lleva a cabo de rutina una evaluación audiológica en los pacientes con fibrosis quística (CF); consecuentemente, la incidencia de hipoacusia no está bien establecida. Objetivo: Documentar la incidencia de trastornos auditivos en niños con fibrosis quística (CF). Diseño: Se evaluó la función auditiva de 45 niños del Hospital Great Ormon Street, usando audiometría de tonos puros hasta 20kHz y DPOAE hasta 8 kHz. Muestra Del Estudio: 39/45 participantes habían recibido AG intravenosos (IV), 23 de los cuáles los recibieron repetidamente por vía IV, cada 3 meses. Resultados: En este grupo de alta exposición, 8 niños (21%) mostraban claros signos de ototoxicidad; los umbrales promedio de 8-20 kHz estaban elevados por ∼50dB y las amplitudes de las DPOAE estaban >10dB más bajas en f2 3.2-6.3 kHz. Los restantes 31/39 (79%) pacientes expuestos a AG tenían una audición normal e incluso, excepcionalmente buena. La incidencia de ototoxicidad del 21% que observamos es sustancial y es más alta de lo previamente reportado. Sin embargo, nuestro hallazgo de audición normal en niños con exposición equivalente a AG sugiere fuertemente que otros factores desconocidos, posiblemente la susceptibilidad genética, influyen en los resultados. Conclusiones: Recomendamos evaluaciones auditivas similares en todos los pacientes con CF con alta exposición a AG. El análisis genético puede ayudar a explicar la dicotomía encontrada en cuanto a la respuesta a AG.

5 mHz oscillations in OAE intensity following sound exposure

Otoacoustic emission (OAE) intensity is highly stable in healthy ears but can be temporarily reduced following noise exposure. This reduction in OAE intensity is well correlated with temporary noise induced hearing threshold elevation and is presumed to be due to metabolic fatigue in the outer hair cells. These cells are responsible for the generation of OAEs and are essential for the maintenance of normal hearing threshold. The severity and recovery of post exposure OAE reduction in an individual is therefore of interest for hearing protection purposes. This paper concerns the regulation of outer hair cell status and the effect of overstimulation on that regulation. We measured OAE level fluctuations following mild over stimulation (e.g., 100 dBSPL for 2 ms) in order to observe the dynamics of OAE regulation. We propose this parallels outer hair cell physiological regulation. Under‐damped oscillations in OAE level occur typically at a frequency of 5 milliHertz after sound exposure. We find oscillations a...