May - July 2002 : Mechanisms of DPOAE Generation

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Category: Guest editorial
Last Updated on Monday, 31 March 2014 13:32
Written by Glen Martin, PhD
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1.  Introduction

        This article presents a brief review of current knowledge and issues regarding the fundamental mechanisms of distortion-product otoacoustic emission (DPOAE) generation. Before discussing the specifics of the relevant DPOAE research, a more general framework, from which DPOAEs can be viewed with regard to the other otoacoustic emission (OAE) subtypes, is presented.

        The traditional categorization of OAEs often divides them simply into two categories based upon the stimulus parameters needed to evoke the specific classes of OAEs (Probst et al 1991). For example, spontaneous OAEs (SOAEs) are in a class of their own in that no stimulus is required to evoke these emissions. Transient-evoked OAEs (TEOAEs), stimulus-frequency OAEs (SFOAEs), and DPOAEs are placed in the other category referred to as the stimulus-evoked emissions in that all these OAEs are elicited by applying deliberate acoustic stimulation to the ear. A major limitation of this simple classification scheme is that little information is provided about the mechanisms of generation for the unique subtypes of OAEs. Generally, under this schema, all OAEs are assumed to arise from the same nonlinear mechanical workings that underlie cochlear processing (eg, Kemp 1978; Kemp & Brown 1983). Recently, Shera and Guinan (1999) presented a taxonomy for mammalian OAEs that can be experimentally verified (Kalluri & Shera 2001). In this conceptualization, Shera and Guinan (1999) proposed that OAEs arise from two fundamentally different mechanisms. Thus, there are OAEs that arise by linear reflection and those that are generated by nonlinear distortion. This distinction [see Fig 10 in Shera & Guinan (1999)] forms a 'family tree' of OAEs in which TEOAEs, SFOAEs, and SOAEs are based upon linear reflections, whereas DPOAEs are produced mainly from nonlinearities acting as emission sources. This classification system is extremely useful in that OAEs can be categorized based upon their mechanisms of generation. Thus, the familiar click-evoked TEOAEs come from reflection off of pre-existing micromechanical impedance perturbations, distributed along the organ of Corti, which might include such conditions as disorganized outer hair cell (OHC) arrays (eg, Lonsbury-Martin et al 1988), that are unique to each cochlea. On the other hand, DPOAEs arise primarily from nonlinear elements in the cochlea that are stimulated by the in-coming traveling waves. What is most important to realize is that OAEs recorded in the ear canal, especially in humans, are rarely due purely to one form or the other, but represent a mixture of the two emission sources. This point will be further addressed, below when the locations along the cochlear partition, from which DPOAEs appear to originate, are discussed. But, first, DPOAEs generated by nonlinear distortion, without any components attributable to linear reflection, are considered.



2. Cochlear Mechanics

       For the moment, we will consider the cochlea simply as a black box and the ear-canal signal as representing the output of this system. Into this black box, two pure tones are applied which, traditionally, are referred to as the f1 and f2 primaries (f1<f2). If the cochlea acts in a linear manner, then we would expect that the output frequencies would be the same as the input frequencies. In other words, the function relating the input to the output signal is a straight line representing a linear function. However, if the function relating the input of the two sinusoids to the output is not a straight line, that is, the input/output (I/O) function is nonlinear, then new frequencies will be generated at the output. I/O functions that are typically used to represent the basilar membrane (BM) response are described in Fig 3 in Fahey et al (2000). One of these I/O plots (Fig 3b) is highly similar in shape to the hair cell receptor voltage versus stereocillia displacement function measured earlier by Hudspeth and Corey (1977) and Russell et al (1986). These types of nonlinear I/O functions obtained from various cochlear structures are relevant to the discussion of physical mechanism(s) within the cochlea that are capable of generating DPOAEs. If such functions exhibit both even- and odd-order symmetry, then all the DPOAEs that can be found in the ear-canal signal will be observed. Thus, combinations of the primaries that result in even-order DPOAEs, such as the simple difference tone, f2-f1, and many odd-order DPOAEs, the largest and most commonly studied one being the 2f1-f2 frequency, will be measured. Other DPOAEs often seen are the lower odd-order sideband 3f1-2f2 and the upper odd-order sideband DPOAE at the 2f2-f1 frequency.

        When the f1 and f2 primaries are presented to the ear canal, the first constraints that must be placed upon DPOAE generation can be appreciated from observations of the underlying BM mechanics [for a recent excellent review, see Robles and Ruggero, (2001)]. Presentation of a pure tone to the ear canal results in the well-known traveling wave of displacement on the BM, that peaks at its characteristic frequency (CF), and then rapidly dies out at more apical points that are lower in frequency. This displacement pattern defines the place on the BM where DPOAEs must be generated. That is, the only place where f1 and f2 can mix in the nonlinearity (often assumed to be based in the OHCs--see below) is in the tail of the BM displacement of the f1 primary. If f2 is placed at a much higher frequency, then, because of the steep apical cutoff of BM displacement, f2 cannot substantially interact with f1. Consequently, on theoretical grounds, DPOAEs must be produced at, or near to, the f2 place, where the two primaries can physically interact on the BM.

        This theoretical prediction is borne out by findings from suppression studies in which a third tone (f3) is used to interfere with DPOAE generation. By sweeping f3 in level and frequency, suppression tuning curves (STCs) can be produced, with their tips typically tuned near the f2 place for the 2f1-f2 DPOAE (eg, Brown & Kemp 1984; Martin et al 1998a). Much of this requirement also accounts for the much studied f2/f1 ratio effect, in which DPOAE levels decrease on either side of an optimum ratio value. In humans, this ideal f2/f1 ratio is approximately 1.22, and DPOAEs are largest at this ideal separation of the two primary tones. Some of this ratio effect, as the primary f1 and f2 tones come closer together, may be due to mutual suppression or interaction of multiple DPOAEs (Stover et al 1996a). It has also been proposed that this phenonmenon can be explained by a second-filter effect (Brown et al 1992).

        When DPOAEs are produced in the cochlea, they can be seen on the BM, and they propagate just as if they were external tones introduced into the ear canal (Robles & Ruggero, 2001). Because the 2f1-f2 is lower in frequency than the f2 place where it is generated, this combination tone will not be perceived, if someone is deaf at this lower frequency. Such an outcome occurs because the 2f1-f2 DPOAE travels to its characteristic place, where it then acts like an external tone.

        Basilar-membrane mechanics also explain why DPOAE are more effectively produced at lower primary-tone levels, when the level of f2, ie, L2, is lower than the level of f1, ie, L1. This is the familiar unequal-level primary tones protocol, typically 65/55 dB SPL, that is almost universally advocated in the clinical literature (Stover et al 1996b) for obtaining DPOAEs in humans. The rationale for lowering L2 is to equate the amplitudes of the vibration of the traveling waves representing the two primaries, where they interact on the BM. Because the BM response is highly compressive at the CF, assumed to be f2 for DPOAEs, and linear at the off-CF frequency of f1, then lowering the level of f2, where it is 'amplified' at low stimulus levels, helps to equate the two stimuli, where they interact at the f2 place [see Fig 4 in Kummer et al (2000) for a superb explanation of this phenomenon]. As primary-tone levels become higher, this L1-L2 difference is no longer needed to equate the two stimuli, a point often not appreciated in the clinical literature (Whitehead et al 1995).



3. DPOAE Generation Mechanisms

        In short, DPOAEs are produced when the primary tones interact on the BM to stimulate nonlinear elements in the cochlea. There is now very convincing evidence that the OHCs are the site of this nonlinearity (Brownell 1990). Specifically, it has been proposed that OHC electromotility, first described by Brownell et al (1985), is the source of the 'cochlear amplifier'. That is, it is assumed that the OHC electromotility-based cochlear amplifier is responsible for the compressive BM response at CF, and the associated sharpness of nerve-fiber tuning seen in physiologically healthy preparations, but absent in damaged or dead animals (Robles & Ruggero 2001), along with the nonlinearity responsible for producing DPOAEs. However, other sources have been proposed for the cochlear amplifier including stereocillia motility (Martin et al 2000). Ultimately, it will probably be discovered that DPOAEs originate from a variety of nonlinear sources, besides OHC electromotility, that participate in the OHC-transduction process including opening and closing of transduction channels (Patuzzi 1998), nonlinearities in stereocillia-bundle motion (Jaramillo et al 1993), and asymmetries in stereocillia stiffness (Khanna & Hao 1993).

        Related to the question of how DPOAEs are generated is the issue of where do DPOAEs originate from with respect to a point(s) along the cochlear partition. As discussed above, it is generally assumed that DPOAEs come from the f2 place. However, once created, DPOAEs also propagate as traveling waves along the BM. Consequently, it is possible for a propagated DPOAE to stimulate the DPOAE place, ie, the 2f1-f2 frequency place, where other OAEs can be further produced by the mechanism of linear-coherent reflection (eg, Heitmann et al 1998; Kalluri & Shera 2001). These two sources (ie, the DPOAE generated at the f2 place and the emissions reflected from the 2f1-f2 DPOAE place) then mix to form the final ear-canal signal.

        Evidence also exists for basal DPOAE sources that may also contribute to the final DPOAE signal. These basal sources are revealed as secondary regions of suppression or enhancement above f2 during the collection of the STCs mentioned above. Such regions of suppression/enhancement are observed at frequencies that are more than an octave above f2 (Martin et al 1999; Mills 2000), where it is unreasonable for the f3, due to the steep apical cutoff of the traveling wave, to affect the f2 place. One possible explanation for these phenomena is that a harmonic of f1 (ie, 2f1) interacts with f2 to produce a simple difference-tone DPOAE. This emission will always have the same frequency as the 2f1-f2, so, depending upon the phase of the difference tone, either suppression or enhancement could result (Fahey et al 2000). Another possibility is that f3 acts as a catalyst to produce difference-tone DPOAEs by more complicated routes that can then interact with the 2f1-f2 DPOAE. Evidence for both possibilities seems to be present in the data.

        Another difficult-to-explain finding is the observation that the upper sideband 2f2-f1 DPOAE appears to originate from its characteristic place on the BM (Martin et al 1998b). As discussed above, this finding contrasts with the notion that all DPOAEs must be generated at the f2 place, where the two traveling waves representing f1 and f2 optimally interact. One possibility is that the 2f2-f1 observed in the ear canal comes largely from a difference-tone DPOAE based upon the interaction of a harmonic of f2 (ie, 2f2) and f1, which of course, will be at the 2f2-f1 frequency.

        A final issue that must be discussed regarding DPOAEs is the notion that there are 'active' versus 'passive' DPOAEs. This conceptualization originated from earlier studies like Norton and Rubel (1990) and Whitehead et al (1992a,b). In these investigations, administration of loop diuretics, such as ethacrynic acid or fursosemide, eliminated low-level DPOAEs, while DPOAEs evoked by high-level tones remained relatively unaffected [see Fig 3 in Whitehead et al (1992)]. Results like these led to the notion that DPOAEs evoked by high-level tones were not relevant to cochlear function, and many clinical studies focused on low-level primaries in the 55- to 65-dB SPL range. However, early studies in humans (Lonsbury-Martin et al 1990) clearly indicate that 75/75 dB SPL equilevel primaries can accurately track the pattern of hearing loss in individuals with impaired hearing. More recently, studies in mice with age-related hearing loss (Jimenez et al 1999) indicate that all levels of primaries accurately follow the progressive degeneration of high-frequency OHCs observed in these animals. Similarly, a brief exposure to damaging levels of noise will affect, not only low-level DPOAEs, but high-level DPOAEs as well (Howard et al 2001). Thus, more recent thinking assumes that there are not two sources of DPOAEs, that is, a low-level 'active' one along with a high-level 'passive' source. Rather, low-level DPOAEs are based upon a functional cochlear amplifier, whereas high-level DPOAEs arise when stimulation is sufficient to move the BM without amplification, in turn, stimulating remaining nonlinear elements to evoke DPOAEs.



4. Summary

In summary, it is clear that we know considerably more regarding DPOAEs generation than when DPOAEs were originally described over 20 years ago (Kemp 1979). In fact, we now have enough confidence in DPOAEs to use them to tell us about the functional status of the cochlea, which now is routinely done in a number of clinical applications including newborn hearing-screening programs. However, we now also realize that DPOAEs measured in the ear canal are considerably more complex than originally envisioned. The newly appreciated complexity of DPOAEs, however, should not be viewed negatively but, rather, should be seen as a further opportunity to extract more information about cochlear function, that will ultimately improve the utility of these emissions as a clinical test.



5. References

 

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  • Brown AM, Gaskill SA, Williams DM (1992): Mechanical filtering of sound in the inner ear. Proc Roy Soc Lond B 250:29-34.

  • Brownell WE (1990): Outer hair cell electromotility and otoacoustic emissions. Ear Hear 11:82-92.

  • Brownell WE, Bader CR, Bertrand D, Ribaupierre Y (1985): Evoked mechanical responses of isolated outer hair cells. Science 227:194-196.

  • Fahey PF, Stagner BB, Lonsbury-Martin BL, Martin GK (2000): Nonlinear interactions that could explain distortion product interference response areas. J Acoust Soc Am 108:1786-1802.

  • Heitmann J, Waldmann B, Schnitzler H-U, Plinkert PK, Zenner H-P (1998): Suppression of distortion product otoacoustic emissions (DPOAE) near 2f1-f2 removes DP-gram fine structure--Evidence for a secondary generator. J Acoust Soc Am 103:1527-1531.

  • Howard MA, Stagner BB, Lonsbury-Martin BL, Martin GK (2002): Effects of reversible noise exposure on the suppression tuning of rabbit distortion-product otoacoustic emissions. J Acoust Soc Am 111:285-296.

  • Hudspeth AJ, Corey DP (1977): Sensitivity, polarity, and conductance change in the response of vertebrate hair cells to controlled mechanical stimuli. Proc Natl Acad Sci USA 74:2407-2411.

  • Jaramillo F, Markin VS, Hudspeth AJ (1993): Auditory illusions and the single hair cell. Nature 364:527-529.

  • Jimenez AM, Stagner BB, Martin GK, Lonsbury-Martin BL (1999): Age-related loss of distortion-product otoacoustic emissions in four mouse strains. Hear Res 138:91-105.

  • Kalluri R, Shera CA (2001): Distortion-product source unmixing: A test of the two-mechanism model for DPOAE generation. J Acoust Soc Am 109:622-637.

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  • Kemp DT (1979): Evidence of mechanical nonlinearity and frequency selective wave amplification in the cochlea. Arch Otorhinolaryngol 224:37-45.

  • Kemp DT, Brown AM (1983): An integrated view of cochlear mechanical nonlinearities observable from the ear canal. In: Mechanics of Hearing, E de Boer, MA Viergever (Eds). Delft, Delft Univ Pr, pp75-82.

  • Khanna SM, Hao LF (1999): Nonlinearity in the apical turn of living guinea pig cochleap. Hear Res 135:89-104.

  • Kummer P, Janssen T, Hulin P, Arnold W (2000): Optimal L1-L2 primary tone level separation remains independent of test frequency in humans. Hear Res 146:47-56.

  • Lonsbury-Martin BL, Martin GK, Probst R, Coats AC (1988): Spontaneous otoacoustic emissions in a nonhuman primate: II. Cochlear anatomy. Hear Res 33:69-94.

  • Lonsbury-Martin BL, Harris FP, Hawkins MD, Stagner BB, Martin GK (1990): Distortion-product emissions in humans: I. Basic properties in normally hearing subjects. Ann Otol Rhinol Laryngol 99, Suppl 147:3-13.

  • Martin GK, Jassir D, Stagner BB, Lonsbury-Martin BL (1998a): Effects of loop diuretics on the suppression tuning of distortion-product otoacoustic emissions in rabbits. J Acoust Soc Am 104:972-983.

  • Martin GK, Jassir D, Stagner BB, Whitehead ML, Lonsbury-Martin BL (1998b): Locus of generation for the 2f1-f2 vs 2f2-f1 distortion-product otoacoustic emissions in normal-hearing humans revealed by suppression tuning, onset latencies, and amplitude correlations. J Acoust Soc Am 103:1957-1971.

  • Martin GK, Stagner BB, Jassir D, Telischi FF, Lonsbury-Martin BL (1999): Suppression and enhancement of distortion-product otoacoustic emissions by interference tones above f2: I. Basic findings in rabbits. Hear Res 136:105-123.

  • Martin P, Mehta AD, Hudspeth AJ (2000): Negative hair-bundle stiffness betrays a mechanism for mechanical amplification by the hair cell. Proc Natl Acad Sci USA 97:12026-12031.

  • Mills DM (2000): Frequency responses of two- and three-tone distortion product otoacoustic emissions in Mongolian gerbils. J Acoust Soc Am 107:2586-2602.

  • Norton SJ, Rubel EW (1990): Active and passive ADP components in mammalian and avian ears. In: Mechanics and Biophysics of Hearing, P Dallos, CD Geisler, JW Matthews, MA Ruggero, CR Steele (Eds). New York: Springer-Verlag, pp219-226.
  • Patuzzi R (1998): A four-state kinetic model of the temporary threshold shift after loud sound based on inactivation of hair cell transduction channels. Hear Res 125:39-70.

  • Probst R, Lonsbury-Martin BL, Martin GK (1991): A review of otoacoustic emissions. J Acoust Soc Am 89:2027-2067.

  • Robles L, Ruggero MA (2001): Mechanics of the mammalian cochlea. Physiol Rev 81:1305-1352.

  • Russell IJ, Cody A, Richardson G (1986): The responses of inner and outer hair cells in the basal turn of the guinea pig cochlea and in the mouse cochlea grown in vitro. Hear Res 22:199-216.

  • Shera CA, Guinan JJ Jr (1999): Evoked otoacoustic emissions arise by two fundamentally different mechanisms: A taxonomy for mammalian OAEs. J Acoust Soc Am 105:782-798.

  • Stover LJ, Neely ST, Gorga MP (1996a): Latency and multiple sources of distortion product otoacoustic emissions. J Acoust Soc Am 99:1016-1024.

  • Stover LJ, Gorga MP, Neely ST, Montoya D (1996b): Toward optimizing the clinical utility of distortion product otoacoustic emission measurements. J Acoust Soc Am 100:956-967.

  • Whitehead ML, Lonsbury-Martin BL, Martin GK (1992a): Evidence for two discrete sources of 2f1-f2 distortion-product otoacoustic emission in rabbit: I. Differential dependence on stimulus parameters. J Acoust Soc Am 91:1567-1607.
  • Whitehead ML, Lonsbury-Martin BL, Martin GK (1992b): Evidence for two discrete sources of 2f1-f2 distortion-product otoacoustic emission in rabbit: II. Differential physiological vulnerability. J Acoust Soc Am 92:2662-2682.

  • Whitehead ML, McCoy MJ, Lonsbury-Martin BL, Martin GK (1995): Dependence of distortion-product otoacoustic emissions on primary levels in normal and impaired ears: I. Effects of decreasing L2 below L1. J Acoust Soc Am 97:2346-2358.



5. Contributing Author

 

Glen K Martin, Ph.D.
Department of Otolaryngology (B205)
University of Colorado Health Sciences Center
4200 East Ninth Ave, Denver CO 80262
303-315-1568 (voice)
303-315-8787 (fax)