Hearing sensitivity and amplitude coding in bats are differentially shaped by echolocation calls and social calls.

Differences in auditory perception between species are influenced by phylogenetic origin and the perceptual challenges imposed by the natural environment, such as detecting prey- or predator-generated sounds and communication signals. Bats are well suited for comparative studies on auditory perception since they predominantly rely on echolocation to perceive the world, while their social calls and most environmental sounds have low frequencies. We tested if hearing sensitivity and stimulus level coding in bats differ between high and low-frequency ranges by measuring auditory brainstem responses (ABRs) of 86 bats belonging to 11 species. In most species, auditory sensitivity was equally good at both high- and low-frequency ranges, while amplitude was more finely coded for higher frequency ranges. Additionally, we conducted a phylogenetic comparative analysis by combining our ABR data with published data on 27 species. Species-specific peaks in hearing sensitivity correlated with peak frequencies of echolocation calls and pup isolation calls, suggesting that changes in hearing sensitivity evolved in response to frequency changes of echolocation and social calls. Overall, our study provides the most comprehensive comparative assessment of bat hearing capacities to date and highlights the evolutionary pressures acting on their sensory perception.

Ocular and cervical vestibular evoked myogenic potentials elicited by air-conducted, low-frequency sound.

BACKGROUND: Sound is not only detected by the cochlea, but also, at high intensities, by the vestibular system. Acoustic activation of the vestibular system can manifest itself in vestibular evoked myogenic potentials (VEMPs). In a clinical setting, VEMPs are usually evoked with rather high-frequency sound (500 Hz and higher), despite the fact that only a fraction of saccular and utricular hair cells in the striolar region is available for high-frequency stimulation. OBJECTIVE: As a growing proportion of the population complains about low-frequency environmental noise, including reports on vestibular symptoms, the activation of the vestibular system by low-frequency sound deserves better understanding. METHODS: We recorded growth functions of oVEMPs and cVEMPs evoked with air-conducted sound at 120 Hz and below. We estimated VEMP thresholds and tested whether phase changes of the stimulus carrier result in changes of VEMP amplitude and latency. RESULTS: The VEMP response of the otholith organs to low-frequency sound is uniform and not tuned when corrected for middle ear attenuation by A-weighting the stimulus level. Different stimulus carrier phases result in phase-correlated changes of cVEMP latencies and amplitudes. CONCLUSIONS: VEMPs can be evoked with rather low-frequency sound, but high thresholds suggest that they are unlikely to be triggered by environmental sounds.

Urocortin 3 signalling in the auditory brainstem aids recovery of hearing after reversible noise-induced threshold shift.

KEY POINTS: Ongoing, moderate noise exposure does not instantly damage the auditory system but may cause lasting deficits, such as elevated thresholds and accelerated ageing of the auditory system. The neuromodulatory peptide urocortin-3 (UCN3) is involved in the body's recovery from a stress response, and is also expressed in the cochlea and the auditory brainstem. Lack of UCN3 facilitates age-induced hearing loss and causes permanently elevated auditory thresholds following a single 2 h noise exposure at moderate intensities. Outer hair cell function in mice lacking UCN3 is unaffected, so that the observed auditory deficits are most likely due to inner hair cell function or central mechanisms. Highly specific, rather than ubiquitous, expression of UCN3 in the brain renders it a promising candidate for designing drugs to ameliorate stress-related auditory deficits, including recovery from acoustic trauma. ABSTRACT: Environmental acoustic noise is omnipresent in our modern society, with sound levels that are considered non-damaging still causing long-lasting or permanent changes in the auditory system. The small neuromodulatory peptide urocortin-3 (UCN3) is the endogenous ligand for corticotropin-releasing factor receptor type 2 and together they are known to play an important role in stress recovery. UCN3 expression has been observed in the auditory brainstem, but its role remains unclear. Here we describe the detailed distribution of UCN3 expression in the murine auditory brainstem and provide evidence that UCN3 is expressed in the synaptic region of inner hair cells in the cochlea. We also show that mice with deficient UCN3 signalling experience premature ageing of the auditory system starting at an age of 4.7 months with significantly elevated thresholds of auditory brainstem responses (ABRs) compared to age-matched wild-type mice. Following a single, 2 h exposure to moderate (84 or 94 dB SPL) noise, UCN3-deficient mice exhibited significantly larger shifts in ABR thresholds combined with maladaptive recovery. In wild-type mice, the same noise exposure did not cause lasting changes to auditory thresholds. The presence of UCN3-expressing neurons throughout the auditory brainstem and the predisposition to hearing loss caused by preventing its normal expression suggests UCN3 as an important neuromodulatory peptide in the auditory system's response to loud sounds.

Slow oscillatory changes of DPOAE magnitude and phase after exposure to intense low-frequency sounds.

Sensitive sound detection within the mammalian cochlea is performed by hair cells surrounded by cochlear fluids. Maintenance of cochlear fluid homeostasis and tight regulation of intracellular conditions in hair cells are crucial for the auditory transduction process but can be impaired by intense sound stimulation. After a short, intense low-frequency sound, the cochlea shows the previously described "bounce phenomenon," which manifests itself as slow oscillatory changes of hearing thresholds and otoacoustic emissions. In this study, distortion product otoacoustic emissions (DPOAEs) were recorded after Mongolian gerbils were exposed to intense low-frequency sounds (200 Hz, 100 dB SPL) with different exposure times up to 1 h. After all sound exposure durations, a certain percentage of recordings (up to 80% after 1.5-min-long exposure) showed oscillatory DPOAE changes, similar to the bounce phenomenon in humans. Changes were quite uniform with respect to size and time course, and they were independent from sound exposure duration. Changes showed states of hypo- and hyperactivity with either state preceding the other. The direction of changes was suggested to depend on the static position of the cochlear operating point. As assessed with DPOAEs, no indication for a permanent damage after several or long exposure times was detected. We propose that sensitivity changes occur due to alterations of the mechanoelectrical transduction process of outer hair cells. Those alterations could be induced by different challenged homeostatic processes with slow electromotility of outer hair cells being the most plausible source of the bounce phenomenon. NEW & NOTEWORTHY Low-frequency, high-intensity sound can cause slowly cycling activity changes in the mammalian cochlea. We examined the effect of low-frequency sound duration on the degree of these alterations. We found that cochlear changes showed a stereotypical biphasic pattern independent of sound exposure duration, but the probability that significant changes occurred decreased with increasing sound duration. Despite exposure durations of up to 1 h, no permanent or transient impairments of the cochlea were detected.

A Comparison of Distortion Product Otoacoustic Emission Properties in Ménière's Disease Patients and Normal-Hearing Participants.

OBJECTIVES: Postmortem examination of temporal bones of Ménière's disease patients consistently show dilated endolymphatic spaces of the inner ear, for which the term endolymphatic hydrops has been coined. During the past decade, magnetic resonance imaging techniques for the inner ear appeared, advancing the diagnosis of Ménière's disease. They require, however, a field-strength of at least 3 T, are costly and not universally available. Alternative, noninvasive, cost-effective tests with high sensitivity and specifity for endolymphatic hydrops are desirable. In this study, we test the suitability of distortion product otoacoustic emissions (DPOAEs) for endolymphatic hydrops detection. Previous measurements of the commonly recorded cubic DPOAEs mainly register cochlear hearing loss and are not specific for Ménière's disease. Simultaneous recordings of cubic and quadratic DPOAEs might be more suitable to detect endolymphatic hydrops, because both DPOAE orders react differently to changes of the cochlear operating point as they might occur in Ménière's disease patients. DESIGN: Cubic and quadratic DPOAEs were recorded in normal-hearing participants (N = 45) and in the affected and unaffected ears of patients with a diagnosis of definite Ménière's disease (N = 32). First, to assess the integrity of DPOAE-generating mechanisms, cubic DPOAE-grams were obtained with primary tone frequencies f2 between 1 and 8 kHz with primary tone levels l1 = 60 dB SPL and l2 = 50 dB SPL, and a fixed primary tone frequency ratio of 1.22. Then, cubic and quadratic DPOAEs were simultaneously recorded with primary tone levels l1 = l2 = 65 dB SPL and at primary tone frequencies f2 = 4 and 5 kHz, where f1 was successively varied such that the ratio f2/f1 ranged between 1.1 and 1.6 in 0.04 steps while quadratic and cubic DPOAE levels were extracted from the same recording. RESULTS: Cubic DPOAEs were significantly reduced in the affected ears of Ménière's disease patients, and slightly reduced in the unaffected ears of Ménière's disease patients, relative to the ears of normal-hearing participants. In contrast, no significant changes could be seen in quadratic DPOAEs across the ears of normal-hearing participants and Ménière's disease patients. CONCLUSIONS: We could identify a relatively good preservation of quadratic DPOAE levels in relation to a reduction of cubic DPOAE levels as a potential noninvasive diagnostic approach in the early stage of suspected Ménière's disease. Future studies validating the differential diagnostic power of this parameter in control groups with nonhydropic forms of hearing loss are warranted.

Modulation of auditory percepts by transcutaneous electrical stimulation.

Transcutaneous, electrical stimulation with electrodes placed on the mastoid processes represents a specific way to elicit vestibular reflexes in humans without active or passive subject movements, for which the term galvanic vestibular stimulation was coined. It has been suggested that galvanic vestibular stimulation mainly affects the vestibular periphery, but whether vestibular hair cells, vestibular afferents, or a combination of both are excited, is still a matter of debate. Galvanic vestibular stimulation has been in use since the late 18th century, but despite the long-known and well-documented effects on the vestibular system, reports of the effect of electrical stimulation on the adjacent cochlea or the ascending auditory pathway are surprisingly sparse. The present study examines the effect of transcutaneous, electrical stimulation of the human auditory periphery employing evoked and spontaneous otoacoustic emissions and several psychoacoustic measures. In particular, level growth functions of distortion product otoacoustic emissions were recorded during electrical stimulation with alternating currents (2 Hz, 1-4 mA in 1 mA-steps). In addition, the level and frequency of spontaneous otoacoustic emissions were followed before, during, and after electrical stimulation (2 Hz, 1-4 mA). To explore the effect of electrical stimulation on the retrocochlear level (i.e. on the ascending auditory pathway beyond the cochlea), psychoacoustic experiments were carried out. Specifically, participants indicated whether electrical stimulation (4 Hz, 2 and 3 mA) induced amplitude modulations of the perception of a pure tone, and of auditory illusions after presentation of either an intense, low-frequency sound (Bounce tinnitus) or a faint band-stop noise (Zwicker tone). These three psychoacoustic measures revealed significant perceived amplitude modulations during electrical stimulation in the majority of participants. However, no significant changes of evoked and spontaneous otoacoustic emissions could be detected during electrical stimulation relative to recordings without electrical stimulation. The present findings show that cochlear function, as assessed with spontaneous and evoked otoacoustic emissions, is not affected by transcutaneous electrical stimulation, at the currents used in this study. Psychoacoustic measures like pure tone perception, but also auditory illusions, are affected by electrical stimulation. This indicates that activity of the retrocochlear ascending auditory pathway is modulated during transcutaneous electrical stimulation.

Aftereffects of Intense Low-Frequency Sound on Spontaneous Otoacoustic Emissions: Effect of Frequency and Level.

The presentation of intense, low-frequency (LF) sound to the human ear can cause very slow, sinusoidal oscillations of cochlear sensitivity after LF sound offset, coined the "Bounce" phenomenon. Changes in level and frequency of spontaneous otoacoustic emissions (SOAEs) are a sensitive measure of the Bounce. Here, we investigated the effect of LF sound level and frequency on the Bounce. Specifically, the level of SOAEs was tracked for minutes before and after a 90-s LF sound exposure. Trials were carried out with several LF sound levels (93 to 108 dB SPL corresponding to 47 to 75 phons at a fixed frequency of 30 Hz) and different LF sound frequencies (30, 60, 120, 240 and 480 Hz at a fixed loudness level of 80 phons). At an LF sound frequency of 30 Hz, a minimal sound level of 102 dB SPL (64 phons) was sufficient to elicit a significant Bounce. In some subjects, however, 93 dB SPL (47 phons), the lowest level used, was sufficient to elicit the Bounce phenomenon and actual thresholds could have been even lower. Measurements with different LF sound frequencies showed a mild reduction of the Bounce phenomenon with increasing LF sound frequency. This indicates that the strength of the Bounce not only is a simple function of the spectral separation between SOAE and LF sound frequency but also depends on absolute LF sound frequency, possibly related to the magnitude of the AC component of the outer hair cell receptor potential.

Responses of the Human Inner Ear to Low-Frequency Sound.

The perceptual insensitivity to low frequency (LF) sound in humans has led to an underestimation of the physiological impact of LF exposure on the inner ear. It is known, however, that intense, LF sound causes cyclic changes of indicators of inner ear function after LF stimulus offset, for which the term "Bounce" phenomenon has been coined.Here, we show that the mechanical amplification of hair cells (OHCs) is significantly affected after the presentation of LF sound. First, we show the Bounce phenomenon in slow level changes of quadratic, but not cubic, distortion product otoacoustic emissions (DPOAEs). Second, Bouncing in response to LF sound is seen in slow, oscillating frequency and correlated level changes of spontaneous otoacoustic emissions (SOAEs). Surprisingly, LF sound can induce new SOAEs which can persist for tens of seconds. Further, we show that the Bounce persists under free-field conditions, i.e. without an in-ear probe occluding the auditory meatus. Finally, we show that the Bounce is affected by contralateral acoustic stimulation synchronised to the ipsilateral LF sound. These findings clearly demonstrate that the origin of the Bounce lies in the modulation of cochlear amplifier gain. We conclude that activity changes of OHCs are the source of the Bounce, most likely caused by a temporary disturbance of OHC calcium homeostasis. In the light of these findings, the effects of long-duration, anthropogenic LF sound on the human inner ear require further research.

Tinnitus in Normal-Hearing Participants after Exposure to Intense Low-Frequency Sound and in Ménière's Disease Patients.

Tinnitus is one of the three classical symptoms of Ménière's disease (MD), an inner ear disease that is often accompanied by endolymphatic hydrops. Previous studies indicate that tinnitus in MD patients is dominated by low frequencies, whereas tinnitus in non-hydropic pathologies is typically higher in frequency. Tinnitus of rather low-frequency (LF) quality was also reported to occur for about 90 s in normal-hearing participants after presentation of intense, LF sound (120 dB SPL, 30 Hz, 90 s). LF sound has been demonstrated to also cause temporary endolymphatic hydrops in animal models. Here, we quantify tinnitus in two study groups with chronic (MD patients) and presumably transient endolymphatic hydrops (normal-hearing participants after LF exposure) with a psychophysical procedure. Participants matched their tinnitus either with a pure tone of adjustable frequency and level or with a noise of adjustable spectral shape and level. Sensation levels of matching stimuli were lower for MD patients (mean: 8 dB SL) than for normal-hearing participants (mean: 15 dB SL). Transient tinnitus after LF-exposure occurred in all normal-hearing participants (N = 28). About half of the normal-hearing participants matched noise to their tinnitus, the other half chose a pure tone with frequencies below 2 kHz. MD patients matched their tinnitus with either high-frequency pure tones, mainly above 3 kHz, or with a noise. Despite a significant proportion of MD patients matching low-pass (roaring) noises to their tinnitus, the range of matched stimuli was more heterogeneous than previous data suggested. We propose that in those participants with noise-like tinnitus, the percept is probably generated by increased spontaneous activity of auditory nerve fibers with a broad range of characteristic frequencies, due to an impaired ion balance in the cochlea. For tonal tinnitus, additional mechanisms are conceivable: focal hair cell loss can result in decreased auditory nerve firing and a central auditory overcompensation. Also, normal-hearing participants after LF-exposure experience alterations in spontaneous otoacoustic emissions, which may contribute to a transient tonal tinnitus.

Low-frequency sound exposure causes reversible long-term changes of cochlear transfer characteristics.

Intense, low-frequency sound presented to the mammalian cochlea induces temporary changes of cochlear sensitivity, for which the term 'Bounce' phenomenon has been coined. Typical manifestations are slow oscillations of hearing thresholds or the level of otoacoustic emissions. It has been suggested that these alterations are caused by changes of the mechano-electrical transducer transfer function of outer hair cells (OHCs). Shape estimates of this transfer function can be derived from low-frequency-biased distortion product otoacoustic emissions (DPOAE). Here, we tracked the transfer function estimates before and after triggering a cochlear Bounce. Specifically, cubic DPOAEs, modulated by a low-frequency biasing tone, were followed over time before and after induction of the cochlear Bounce. Most subjects showed slow, biphasic changes of the transfer function estimates after low-frequency sound exposure relative to the preceding control period. Our data show that the operating point changes biphasically on the transfer function with an initial shift away from the inflection point followed by a shift towards the inflection point before returning to baseline values. Changes in transfer function and operating point lasted for about 180 s. Our results are consistent with the hypothesis that intense, low-frequency sound disturbs regulatory mechanisms in OHCs. The homeostatic readjustment of these mechanisms after low-frequency offset is reflected in slow oscillations of the estimated transfer functions.

Concurrent Acoustic Activation of the Medial Olivocochlear System Modifies the After-Effects of Intense Low-Frequency Sound on the Human Inner Ear.

>Human hearing is rather insensitive for very low frequencies (i.e. below 100 Hz). Despite this insensitivity, low-frequency sound can cause oscillating changes of cochlear gain in inner ear regions processing even much higher frequencies. These alterations outlast the duration of the low-frequency stimulation by several minutes, for which the term 'bounce phenomenon' has been coined. Previously, we have shown that the bounce can be traced by monitoring frequency and level changes of spontaneous otoacoustic emissions (SOAEs) over time. It has been suggested elsewhere that large receptor potentials elicited by low-frequency stimulation produce a net Ca(2+) influx and associated gain decrease in outer hair cells. The bounce presumably reflects an underdamped, homeostatic readjustment of increased Ca(2+) concentrations and related gain changes after low-frequency sound offset. Here, we test this hypothesis by activating the medial olivocochlear efferent system during presentation of the bounce-evoking low-frequency (LF) sound. The efferent system is known to modulate outer hair cell Ca(2+) concentrations and receptor potentials, and therefore, it should modulate the characteristics of the bounce phenomenon. We show that simultaneous presentation of contralateral broadband noise (100 Hz-8 kHz, 65 and 70 dB SPL, 90 s, activating the efferent system) and ipsilateral low-frequency sound (30 Hz, 120 dB SPL, 90 s, inducing the bounce) affects the characteristics of bouncing SOAEs recorded after low-frequency sound offset. Specifically, the decay time constant of the SOAE level changes is shorter, and the transient SOAE suppression is less pronounced. Moreover, the number of new, transient SOAEs as they are seen during the bounce, are reduced. Taken together, activation of the medial olivocochlear system during induction of the bounce phenomenon with low-frequency sound results in changed characteristics of the bounce phenomenon. Thus, our data provide experimental support for the hypothesis that outer hair cell calcium homeostasis is the source of the bounce phenomenon.

A novel mechanism of cochlear excitation during simultaneous stimulation and pressure relief through the round window.

The round window (RW) membrane provides pressure relief when the cochlea is excited by sound. Here, we report measurements of cochlear function from guinea pigs when the cochlea was stimulated at acoustic frequencies by movements of a miniature magnet which partially occluded the RW. Maximum cochlear sensitivity, corresponding to subnanometre magnet displacements at neural thresholds, was observed for frequencies around 20 kHz, which is similar to that for acoustic stimulation. Neural response latencies to acoustic and RW stimulation were similar and taken to indicate that both means of stimulation resulted in the generation of conventional travelling waves along the cochlear partition. It was concluded that the relatively high impedance of the ossicles, as seen from the cochlea, enabled the region of the RW not occluded by the magnet, to act as a pressure shunt during RW stimulation. We propose that travelling waves, similar to those owing to acoustic far-field pressure changes, are driven by a jet-like, near-field component of a complex pressure field, which is generated by the magnetically vibrated RW. Outcomes of research described here are theoretical and practical design principles for the development of new types of hearing aids, which use near-field, RW excitation of the cochlea.

The effects of rise/fall time and plateau time on ocular vestibular evoked myogenic potentials.

Ocular vestibular evoked myogenic potentials (oVEMP) are strongly influenced by recording conditions and stimulus parameters. Throughout the published literature, a large variety of stimuli is used for eliciting oVEMP. Our objective was to determine the effects of different rise/fall times and plateau times on oVEMP amplitudes and latencies. 32 healthy subjects were enrolled in the study. 500 Hz air-conducted tone bursts with the parameters rise-plateau-fall time 0-4-0, 4-0-4, 2-2-2 and 2-4-2 ms were used for eliciting oVEMP. For all stimuli, response prevalences were 100 %. The 4-0-4 ms stimulus generated the smallest amplitudes, whereas the 2-2-2 and 0-4-0 ms stimuli achieved the largest amplitudes. n1 and p1 latencies were significantly shorter for the 0-4-0 ms than for the other stimuli, whereas latencies in response to the 4-0-4 ms stimulus were prolonged. Hence, a variety of stimuli is suitable for evoking oVEMP in healthy subjects. We recommend a 2-2-2 ms stimulus for clinical testing of oVEMP elicited by air conducted sound, because it reproducibly generates oVEMP without exposing the ear to unnecessary amounts of acoustic energy.

Low-frequency sound affects active micromechanics in the human inner ear.

Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing.

Effects of acoustic stimuli used for vestibular evoked myogenic potential studies on the cochlear function.

OBJECTIVE: To study if acoustic stimuli used for vestibular evoked myogenic potential (VEMP) studies can damage the cochlea. STUDY DESIGN: Prospective diagnostic study. SETTING: Academic tertiary referral center. METHODS: In 30 young healthy adults aged between 20 and 35 years without any audiovestibular disorders, cVEMP studies were performed in a standard setting (tone burst, 500 Hz, 133 dB SPL, stimuli rate 200). Before and after acoustic stimulation for the cVEMP examination, the cochlear function was measured using pure tone audiometry and distortion product otoacoustic emissions (DPOAE). Additionally, the subjects were asked about ear symptoms. RESULTS: In all subjects, cVEMP could be recorded. Eight (27%) of them reported subjective hearing symptoms direct after the VEMP examination. All were again free of complaints on the next day. Hearing thresholds did not deteriorate in pure tone audiometry. DPOAE levels decreased on the exposed side in the high-frequency range (4,000-6,000 Hz). The subjects with subjective ear symptoms had a stronger level decrease. In a follow-up measurement 24 hours later, the DPOAE levels showed recovery. CONCLUSION: Acoustic stimuli used to elicit VEMP were found to have an adverse effect on the cochlear function. A clinically relevant hearing loss was not found in our study in healthy adults. Subjective auditory symptoms were reversible within 24 hours. Nevertheless, the stimulus levels and the number of repetitions should be kept as low as possible.

Low-frequency modulated quadratic and cubic distortion product otoacoustic emissions in humans.

Previous studies have used low-frequency tones to modulate distortion product otoacoustic emissions (DPOAEs). The cubic DPOAE (CDPOAE) is mostly chosen because amplitudes sufficient for modulation can be evoked with moderate sound pressure levels. Quadratic DPOAEs (QDPOAEs) however, are more sensitive to minute changes of the cochlear operating point (OP) and are better suited to assess changes of the cochlear OP. Here, we compare the properties of low-frequency (30 Hz, 80-120 dB SPL) modulated CDPOAE and QDPOAEs evoked with f(2) = 2 and 5 kHz in human subjects with normal hearing. The modulation depth was quantified with the modulation index (MI), a measure which considers both amplitude and phase. Modulated CDPOAEs evoked with f(2) = 2 kHz have amplitude maxima at the zero crossings and amplitude minima at the extremes of the biasing tone (BT) which correlate positively with the BT level. CDPOAEs evoked with f(2) = 5 kHz were recorded during biasing in exactly the same way as described before. At the highest BT levels used (120 dB SPL), very little modulation could be detected. Not only the depth, but also the shape of the QDPOAE modulation pattern is correlated with the BT level. At moderate BT levels (about 90-100 dB SPL) QDPOAEs evoked with f(2) = 5 kHz show one amplitude notch around the zero crossing of the positive going flank of the BT (a single modulation pattern). At and above a BT level of about 105 dB SPL, the pattern reverses and shows a double modulation pattern. At the highest BT level used (120 dB SPL), quadratic MIs exceed cubic MIs (2.0 ± 0.5 and 0.97 ± 0.06, respectively). Patterns of low-frequency modulated QDPOAEs in humans are similar to the modulation seen in animal studies and as predicted by mathematical models. Human low-frequency modulated QDPOAEs are ideally suited to estimate cochlear OP shifts because of their high sensitivity to the OP shift.

Outer hair cell somatic, not hair bundle, motility is the basis of the cochlear amplifier.

Sensitivity, dynamic range and frequency tuning of the cochlea are attributed to amplification involving outer hair cell stereocilia and/or somatic motility. We measured acoustically and electrically elicited basilar membrane displacements from the cochleae of wild-type and Tecta(DeltaENT/DeltaENT) mice, in which stereocilia are unable to contribute to amplification near threshold. Electrically elicited responses from Tecta(DeltaENT/DeltaENT) mice were markedly similar to acoustically and electrically elicited responses from wild-type mice. We conclude that somatic, and not stereocilia, motility is the basis of cochlear amplification.

The role of prestin in the generation of electrically evoked otoacoustic emissions in mice.

Electrically evoked otoacoustic emissions are sounds emitted from the inner ear when alternating current is injected into the cochlea. Their temporal structure consists of short- and long-delay components and they have been attributed to the motile responses of the sensory-motor outer hair cells of the cochlea. The nature of these motile responses is unresolved and may depend on either somatic motility, hair bundle motility, or both. The short-delay component persists after almost complete elimination of outer hair cells. Outer hair cells are thus not the sole generators of electrically evoked otoacoustic emissions. We used prestin knockout mice, in which the motor protein prestin is absent from the lateral walls of outer hair cells, and Tecta(Delta ENT/Delta ENT) mice, in which the tectorial membrane, a structure with which the hair bundles of outer hair cells normally interact, is vestigial and completely detached from the organ of Corti. The amplitudes and delay spectra of electrically evoked otoacoustic emissions from Tecta(Delta ENT/Delta ENT) and Tecta(+/+) mice are very similar. In comparison with prestin(+/+) mice, however, the short-delay component of the emission in prestin(-/-) mice is dramatically reduced and the long-delay component is completely absent. Emissions are completely suppressed in wild-type and Tecta(Delta ENT/Delta ENT) mice at low stimulus levels, when prestin-based motility is blocked by salicylate. We conclude that near threshold, the emissions are generated by prestin-based somatic motility.

Prestin's role in cochlear frequency tuning and transmission of mechanical responses to neural excitation.

The remarkable power amplifier [1] of the cochlea boosts low-level and compresses high-level vibrations of the basilar membrane (BM) [2]. By contributing maximally at the characteristic frequency (CF) of each point along its length, the amplifier ensures the exquisite sensitivity, narrow frequency tuning, and enormous dynamic range of the mammalian cochlea. The motor protein prestin in the outer hair cell (OHC) lateral membrane is a prime candidate for the cochlear power amplifier [3]. The other contender for this role is the ubiquitous calcium-mediated motility of the hair cell stereocilia, which has been demonstrated in vitro and is based on fast adaptation of the mechanoelectrical transduction channels [4, 5]. Absence of prestin [6] from OHCs results in a 40-60 dB reduction in cochlear neural sensitivity [7]. Here we show that sound-evoked BM vibrations in the high-frequency region of prestin(-/-) mice cochleae are, surprisingly, as sensitive as those of their prestin(+/+) siblings. The BM vibrations of prestin(-/-) mice are, however, broadly tuned to a frequency approximately a half octave below the CF of prestin(+/+) mice at similar BM locations. The peak sensitivity of prestin(+/+) BM tuning curves matches the neural thresholds. In contrast, prestin(-/-) BM tuning curves at their best frequency are >50 dB more sensitive than the neural responses. We propose that the absence of prestin from OHCs, and consequent reduction in stiffness of the cochlea partition, changes the passive impedance of the BM at high frequencies, including the CF. We conclude that prestin influences the cochlear partition's dynamic properties that permit transmission of its vibrations into neural excitation. Prestin is crucial for defining sharp and sensitive cochlear frequency tuning by reducing the sensitivity of the low-frequency tail of the tuning curve, although this necessitates a cochlear amplifier to determine the narrowly tuned tip.

Cochlear sensitivity in the lesser spear-nosed bat, Phyllostomus discolor.

Behavioral auditory thresholds of Phyllostomus discolor are characterized by two threshold minima separated by an insensitive region at about 55 kHz (Esser and Daucher 1996). To investigate whether these characteristics are due to cochlear properties, we recorded distortion product otoacoustic emissions (DPOAEs) and calculated relative DPOAE threshold curves, which proved to be a good measure of cochlear sensitivity. Our results indicate that in P. discolor, cochlear sensitivity, as assessed by DPOAE recordings, does not show a threshold maximum at 55 kHz. The DPOAE threshold curves display an absolute minimum at approximately 30 kHz, and from that frequency region, the threshold continuously increases without any pronounced irregularities. The frequency tuning properties of the cochlea, as assessed by DPOAE suppression tuning curves (STCs) reveal broad filter bandwidths with Q10dB values between 3.4 and 10.7. There are no frequency-specific specializations of cochlear tuning. The characteristic pattern of subsequent threshold maxima and minima at high frequencies observed in behavioral studies seems to be shaped by transfer characteristics of the outer ear and/or neuronal processing in the ascending auditory pathway rather than by cochlear mechanics.