Forward and Reverse Middle Ear Transmission in Gerbil with a Normal or Spontaneously Healed Tympanic Membrane.

Tympanic membranes (TM) that have healed spontaneously after perforation present abnormalities in their structural and mechanical properties; i.e., they are thickened and abnormally dense. These changes result in a deterioration of middle ear (ME) sound transmission, which is clinically presented as a conductive hearing loss (CHL). To fully understand the ME sound transmission under TM pathological conditions, we created a gerbil model with a controlled 50% pars tensa perforation, which was left to heal spontaneously for up to 4 weeks (TM perforations had fully sealed after 2 weeks). After the recovery period, the ME sound transmission, both in the forward and reverse directions, was directly measured with two-tone stimulation. Measurements were performed at the input, the ossicular chain, and output of the ME system, i.e., at the TM, umbo, and scala vestibuli (SV) next to the stapes. We found that variations in ME transmission in forward and reverse directions were not symmetric. In the forward direction, the ME pressure gain decreased in a frequency-dependent manner, with smaller loss (within 10 dB) at low frequencies and more dramatic loss at high frequency regions. The loss pattern was mainly from the less efficient acoustical to mechanical coupling between the TM and umbo, with little changes along the ossicular chain. In the reverse direction, the variations in these ears are relatively smaller. Our results provide detailed functional observations that explain CHL seen in clinical patients with abnormal TM, e.g., caused by otitis media, that have healed spontaneously after perforation or post-tympanoplasty, especially at high frequencies. In addition, our data demonstrate that changes in distortion product otoacoustic emissions (DPOAEs) result from altered ME transmission in both the forward and reverse direction by a reduction of the effective stimulus levels and less efficient transfer of DPs from the ME into the ear canal. This confirms that DPOAEs can be used to assess both the health of the cochlea and the middle ear.

Distortion product otoacoustic emissions: Sensitive measures of tympanic -membrane perforation and healing processes in a gerbil model.

Distortion product otoacoustic emissions (DPOAEs) evoked by two pure tones carry information about the mechanisms that generate and shape them. Thus, DPOAEs hold promise for providing powerful noninvasive diagnostic details of cochlear operations, middle ear (ME) transmission, and impairments. DPOAEs are sensitive to ME function because they are influenced by ME transmission twice, i.e., by the inward-going primary tones in the forward direction and the outward traveling DPOAEs in the reverse direction. However, the effects of ME injuries on DPOAEs have not been systematically characterized. The current study focused on exploring the utility of DPOAEs for examining ME function by methodically characterizing DPOAEs and ME transmission under pathological ME conditions, specifically under conditions of tympanic-membrane (TM) perforation and spontaneous healing. Results indicated that DPOAEs were measurable with TM perforations up to ∼50%, and DPOAE reductions increased with increasing size of the TM perforation. DPOAE reductions were approximately flat across test frequencies when the TM was perforated about 10% (<1/8 of pars tensa) or less. However, with perforations greater than 10%, DPOAEs decreased further with a low-pass filter shape, with ∼30 dB loss at frequencies below 10 kHz and a quick downward sloping pattern at higher frequencies. The reduction pattern of DPOAEs across frequencies was similar to but much greater than, the directly measured ME pressure gain in the forward direction, which suggested that reduction in the DPOAE was a summation of losses of ME ear transmission in both the forward and reverse directions. Following 50% TM perforations, DPOAEs recovered over a 4-week spontaneously healing interval, and these recoveries were confirmed by improvements in auditory brainstem response (ABR) thresholds. However, up to 4-week post-perforation, DPOAEs never fully recovered to the levels obtained with normal intact TM, consistent with the incomplete recovery of ABR thresholds and ME transmission, especially at high-frequency regions, which could be explained by an irregularly dense and thickened healed TM. Since TM perforations in patients are commonly caused by either trauma or infection, the present results contribute towards providing insight into understanding ME transmission under pathological conditions as well as promoting the application of DPOAEs in the evaluation and diagnosis of deficits in the ME-transmission system.

Adaptation of distortion product otoacoustic emissions predicts susceptibility to acoustic over-exposure in alert rabbits.

A noninvasive test was developed in rabbits based on fast adaptation measures for 2f1-f2 distortion-product otoacoustic emissions (DPOAEs). The goal was to evaluate the effective reflex activation, i.e., "functional strength," of both the descending medial olivocochlear efferent reflex (MOC-R) and the middle-ear muscle reflex (MEM-R) through sound activation. Classically, it is assumed that both reflexes contribute toward protecting the inner ear from cochlear damage caused by noise exposure. The DP-gram method described here evaluated the MOC-R effect on DPOAE levels over a two-octave (oct) frequency range. To estimate the related activation of the middle-ear muscles (MEMs), the MEM-R was measured by monitoring the level of the f1-primary tone throughout its duration. Following baseline measures, rabbits were subjected to noise over-exposure. A main finding was that the measured adaptive activity was highly variable between rabbits but less so between the ears of the same animal. Also, together, the MOC-R and MEM-R tests showed that, on average, DPOAE adaptation consisted of a combined contribution from both systems. Despite this shared involvement, the amount of DPOAE adaptation measured for a particular animal's ear predicted that ear's subsequent susceptibility to the noise over-exposure for alert but not for deeply anesthetized rabbits.

Evidence for basal distortion-product otoacoustic emission components.

Distortion-product otoacoustic emissions (DPOAEs) were measured with traditional DP-grams and level/phase (L/P) maps in rabbits with either normal cochlear function or unique sound-induced cochlear losses that were characterized as either low-frequency or notched configurations. To demonstrate that emission generators distributed basal to the f(2) primary-tone contribute, in general, to DPOAE levels and phases, a high-frequency interference tone (IT) was presented at 1/3 of an octave (oct) above the f(2) primary-tone, and DPOAEs were re-measured as "augmented" DP-grams (ADP-grams) and L/P maps. The vector difference between the control and augmented functions was then computed to derive residual DP-grams (RDP-grams) and L/P maps. The resulting RDP-grams and L/P maps, which described the DPOAEs removed by the IT, supported the notion that basal DPOAE components routinely contribute to the generation of standard measures of DPOAEs. Separate experiments demonstrated that these components could not be attributed to the effects of the 1/3-oct IT on f(2), or DPOAEs generated by the addition of a third interfering tone. These basal components can "fill in" the lesion estimated by the commonly employed DP-gram. Thus, ADP-grams more accurately reveal the pattern of cochlear damage and may eventually lead to an improved DP-gram procedure.

Comparison of distortion product otoacoustic emissions in 28 inbred strains of mice.

Cochlear function was evaluated in a longitudinal study of 28 inbred strains of mice at 3 and 5 mo of age using measures of distortion product otoacoustic emissions (DPOAEs) in response to a federal initiative to develop rapid mouse phenotyping methodologies. DP-grams at f(2) frequencies ranging from 6.3 to 54.2kHz were obtained in about 3min/ear by eliciting 2f(1)-f(2) DPOAEs in 0.1-octave steps of f(2) with primary tones at L(1)=L(2) =55, 65, and 75dB SPL. CBA/CaJ mice exhibited average levels of approximately 26dB SPL and this strain was selected as the normal reference strain against which the others were compared. Based upon the configurations of their DP-grams, the 28 mouse strains could be categorized into four distinct groups. That is, nine of the strains including the CBA were designated as the CBA-like group because these mice displayed robust DPOAE levels across frequency. In contrast, the remaining three groups all exhibited irregular DP-gram patterns. Specifically, eight of the remaining 19 strains showed a progressive high- to low-frequency reduction in DPOAE levels that was typical of age-related hearing loss (AHL) associated with mouse strains homozygous for the ahl allele and were labeled as AHL-like strains. Seven strains demonstrating relatively even patterns of reduced DPOAE levels across the frequency-test range were designated as Flat-loss strains. Finally, the remaining four strains exhibited no measurable DPOAEs at either 3 or 5 mo of age and thus were classified as Absent strains. Extending the f(2) test frequencies up to approximately 54kHz led to the detection of very early-onset reductions in cochlear function in non-CBA-like groups so that all strains could be categorized by 3 mo of age. Predictably, the AHL-like strains showed more pronounced DPOAE losses at 5 mo than at 3 mo. A similar deterioration in DPOAE levels was not apparent for the Flat-loss strains. Both the AHL-like and Flat-loss strains showed considerably more variability in DPOAE levels than did the CBA-like strains. Together, these findings indicate that DP-grams adequately reveal both frequency-specific loss patterns and details of inbred strain variability.

Human efferent adaptation of DPOAEs in the L1,L2 space.

The adaptive properties of distortion product otoacoustic emissions (DPOAEs) at 2f(1)-f2 were investigated in 12 ears of normally hearing adults aged 18-30 years using long-lasting 1-s primary-tone on-times. In this manner, DPOAE adaptation at a single f2 of 1.55 kHz (f2/f1=1.21) was evaluated as a function of the levels of the primary tones in a matrix of L1, L2 settings, which varied from 45 to 80 dB SPL, in 5-dB steps. DPOAEs were elicited under both monaural and binaural stimulus-presentation conditions. Adaptation was defined as the difference in DPOAE levels between the initial 92-ms baseline measure using a standard protocol and one obtained during the final 92 ms of the prolonged 1-s primary-tones. These differences were averaged across subjects to create contour plots of mean adaptation in the L1,L2 space. The 2f(1)-f2 DPOAE revealed consistent regions of suppression (-0.5 dB difference) or enhancement (+0.5 dB difference) with respect to baseline measures within the L(1),L(2) matrix for both acoustic-stimulation conditions. Specifically, 2f(1)-f2 DPOAE suppressions of 1-2 dB occurred for both monaural and binaural presentations, typically at level combinations in which L1>L2. In contrast, larger 2f(1)-f2 DPOAE enhancements of 3-4 dB occurred for only the binaural condition, at primary-tone level combinations where L1