Relationship between irregularities in spontaneous otoacoustic emissions suppression and psychophysical tuning curves.

The suppression of spontaneous otoacoustic emissions (SOAEs) allows the objective evaluation of cochlear frequency selectivity by determining the suppression tuning curve (STC). Interestingly, some STCs have additional sidelobes at the high frequency flank, which are thought to result from interaction between the probe tone and the cochlear standing wave corresponding to the SOAE being suppressed. Sidelobes are often in regions of other neighboring SOAEs but can also occur in the absence of any other SOAE. The aim of this study was to compare STCs and psychoacoustic tuning curves (PTCs). Therefore, STCs and PTCs were measured in: (1) subjects in which the STC had a sidelobe, and (2) subjects without STC sidelobes. Additionally, PTCs were measured in subjects without SOAEs. Across participant groups, the quality factor Q10dB of the PTCs was similar, independently from whether SOAEs were present or absent. Thus, the presence of an SOAE does not provide enhanced frequency selectivity at the emission frequency. Moreover, both PTC and STC show irregularities, but these are not related in a straightforward way. This suggests that different mechanisms cause these irregularities.

Changes in Tinnitus by Cochlear Implantation: A Parametric Study of the Effect of Single-Electrode Stimulation.

INTRODUCTION: While cochlear implantation may have a positive effect on tinnitus, it is not effective in reducing tinnitus in all patients. This may be due to different patients requiring different strategies of electrical stimulation in order to obtain a positive effect on tinnitus. It is, therefore, important to identify the most effective stimulation strategies to reduce tinnitus. The simplest possible strategy is stimulation by only one electrode. In this study, we investigated tinnitus suppression by electrical stimulation via a single electrode of the cochlear implant. METHODS: We performed a listening experiment in 19 adult participants, who had received a unilateral cochlear implant (CI) because of severe bilateral hearing loss. All of these patients had indicated that they suffered from tinnitus. During a 300-s interval, patients listened to blocks of single-electrode stimulation and rated the loudness of the stimulus and any effects on their tinnitus. The 300-s interval included a block of single-electrode stimulation (duration 120 s). In consecutive intervals, the stimulus differed in its cochlear location (basal or apical), its pulse rate (720 or 725 Hz, 1,200 Hz, and 2,400 or 2,320 Hz), and amplitude (just above threshold or equivalent to moderate loudness). Thus, 2 × 3 × 2 = 12 stimulus conditions were tested in each participant, and each condition was presented only once. During the experiment, the participants promptly rated the loudness of the stimuli and the loudness of their tinnitus on a Visual Analogue Scale (10-point VAS). RESULTS: Significantly more tinnitus reduction was observed with stimuli at a moderate intensity level (30%) compared to stimuli at near-threshold level (18%) (χ2 [1, N = 222] = 14.115, p < 0.01). No significant differences in tinnitus levels resulted from the different pulse rates and stimulation sites. Eight participants reported an increase of tinnitus loudness under at least one stimulus condition. Changes in tinnitus loudness were generally minor, and never exceeded 3 points on the VAS. The overall effect of cochlear implantation on tinnitus, that is, the effect with full-array stimulation, was not correlated with the effectiveness of the single-electrode stimulation on tinnitus. CONCLUSION: In conclusion, the effect of single-electrode stimulation on tinnitus is relatively insignificant in comparison to the effect of full-array stimulation. However, in some individual cases, sustained single-electrode stimulation may be beneficial for tinnitus management.

The relation between perception and brain activity in gaze-evoked tinnitus.

Tinnitus is a phantom sound percept that can be severely disabling. Its pathophysiology is poorly understood, partly due to the inability to objectively measure neural correlates of tinnitus. Gaze-evoked tinnitus (GET) is a rare form of tinnitus that may arise after vestibular schwannoma removal. Subjects typically describe tinnitus in the deaf ear on the side of the surgery that can be modulated by peripheral eye gaze. This phenomenon offers a unique opportunity to study the relation between tinnitus and brain activity. We used functional magnetic resonance imaging in humans to show that in normal-hearing control subjects, peripheral gaze results in inhibition of the auditory cortex, but no detectable response in the medial geniculate body (MGB) and inferior colliculus (IC). In patients with GET, peripheral gaze (1) reduced the cortical inhibition, (2) inhibited the MGB, and (3) activated the IC. Furthermore, increased tinnitus loudness is represented by increased activity in the cochlear nucleus (CN) and IC and reduced inhibition in the auditory cortex (AC). The increase of CN and IC activity with peripheral gaze is consistent with models of plastic reorganization in the brainstem following vestibular schwannoma removal. The activity decrease in the MGB and the reduced inhibition of the AC support a model that attributes tinnitus to a dysrhythmia of the thalamocortical loop, leading to hypometabolic theta activity in the MGB. Our data offer the first support of this loop hypothesis of tinnitus, independent of the initial experiments that led to its formulation.

Can the tinnitus spectrum identify tinnitus subgroups?

The tinnitus spectrum is a psycho-acoustic metric of tinnitus. Previous work found a tight relation between the spectrum and the tone audiogram. This suggests that the spectrum and the audiogram provide essentially the same information, and the added value of the spectrum is limited. In order to test whether the spectrum shows tinnitus characteristics that cannot be inferred from the audiogram, we re-examined the relation between the tinnitus spectrum and the tone audiogram, in a group of 80 tinnitus patients. We defined three subgroups of patients, using the shape of their tinnitus spectrum: (1) patients with a spectrum, monotonously increasing with frequency (2) patients with a distinct peak in their spectrum, (3) all other patients. Patients in group 3 typically showed low frequency tinnitus spectra. In all three groups, the largest hearing loss was at high frequencies (>2 kHz). The mean audiograms of group 1 and 2 were remarkably similar; group 3 had an additional hearing loss for the lower frequencies (<2 kHz). The three groups did not differ with respect to age, sex, or tinnitus questionnaire outcomes. In subgroups 2 and 3, the shape of the spectrum clearly differed from that of the tone audiogram. In other words, the spectrum technique provided information that could not have been obtained by tone audiometry alone. Therefore, the spectrum measurement may develop into a technique that can differentiate between classes of tinnitus. This may eventually contribute to the effective management of tinnitus, as various classes of tinnitus may require different therapeutic interventions.

Comparison between two self-guided tinnitus pitch matching methods.

Introduction: Tinnitus pitch matching is a procedure by which the frequency of an external sound is manipulated in such a way that its pitch matches the one of the tinnitus. The correct measure of the tinnitus pitch plays an important role in the effectiveness of any sound-based therapies. To date, this assessment is difficult due to the subjective nature of tinnitus. Some of the existing pitch matching methods present a challenge for both patients and clinicians, and require multiple adjustments of frequency and loudness, which becomes increasingly difficult in case of coexisting hearing loss. In this paper, we present the comparison in terms of reliability between two self-guided pitch matching methods: the method of adjustment (MOA) and the multiple-choice method (MCM). Methods: 20 participants with chronic tinnitus and hearing loss underwent the two assessments in two different sessions, 1 week apart. Measures of intraclass correlation (ICC) and difference in octaves (OD) within-method and within-session were obtained. Results: Both methods presented good reliability, and the obtained values of ICC and OD suggested that both methods might measure a different aspect of tinnitus. Discussion: Our results suggest that a multiple-choice method (MCM) for tinnitus pitch matching is as reliable in a clinical population as more conventional methods.

[Current diagnostics and treatment options for tinnitus]. / Diagnostiek en behandelopties voor tinnitus.

Tinnitus is a common condition with great variability in the intensity of symptomatology. In recent years, more and more insights have been gained into the mechanism of tinnitus and its relationship with hearing loss and other factors such as stress. Depending on the symptoms and clinical findings, a patient may be referred to an ENT specialist or audiologist. For the majority of patients, re-assurance and providing good information is sufficient. For others improving hearing and possibly cognitive behavioral therapy remains the most important pillars for treatment of tinnitus. A number of experimental treatments are currently underway which offer hope for the future.

Carbamazepine induces upward frequency shifts of spontaneous otoacoustic emissions.

In three subjects, we measured spontaneous otoacoustic emissions (SOAEs) when they were using carbamazepine (CBZ), and compared this to the SOAE measurement when they were not using CBZ. We observed 14 SOAEs showing a consistent upward shift of center frequency, related to CBZ intake. On average, the magnitude of the frequency shift increased with increasing frequency. The magnitude of the shift was 30-104 Hz, at frequencies ranging from 1.3 to 2.3 kHz, corresponding to a shift between 2.3 and 4.5%. Compared to other causes and manipulations known to change SOAE frequency, these shifts are relatively large. The underlying mechanism is most likely an increased stiffness of the cochlear partition. This would also explain the downward pitch shift due to CBZ, which has been reported by subjects with absolute pitch.

Frequency shifts with age in click-evoked otoacoustic emissions of preterm infants.

A previous study [Brienesse et al. (1997). Pediatr. Res. 42, 478-483] demonstrated a positive shift with increasing postmenstrual age (PMA) in the frequencies of synchronized spontaneous otoacoustic emissions (SSOAEs) in preterm infants. We used a mixed model approach to describe a shift with PMA in the spectra of click-evoked otoacoustic emissions (CEOAEs) measured in a group of 22 preterm infants. The rate in shift in CEOAE spectral components was found to be frequency dependent, with a mean estimate of 10 Hz/week for frequencies around 2 kHz and 30 Hz/week for frequencies around 4.25 kHz. This rate decreased with increasing PMA. Because SSOAEs are often part of the CEOAE response, a comparison was made between the shifts in SSOAEs and CEOAEs in a sub-group of 16 preterm infants. The results indicate that the shifts found for both types of OAE are similar, which supports a common mechanism for this change in OAE-characteristic. At present it is not clear to what extent developmental processes in the cochlea and the middle ear can account for these frequency shifts in the spectra of CEOAEs and SSOAEs during the preterm period.

Investigating the relation between minimum masking levels and hearing thresholds for tinnitus subtyping.

Heterogeneity of tinnitus imposes a challenge for its treatment. Identifying tinnitus subtypes might help to establish individualized diagnosis and therapies. The minimum masking level (MML) is a clinical tool defined as the minimum intensity of a masking sound required to cover tinnitus. Understanding the differences among masking patterns in patients could facilitate the task of subtyping tinnitus. Here, we studied the variability of hearing thresholds and MMLs among patients with tinnitus to identify tinnitus subgroups. A population of 366 consecutive patients from a specialized tinnitus clinic were included in the analysis. Hearing thresholds and MMLs were determined for octave frequencies from 0.25 to 8kHz, as well as for 3 and 6kHz. Subjects were divided into two groups according to whether their tinnitus was maskable (M, 329 subjects) or non-maskable (NM, 37 subjects). Hearing thresholds and tinnitus loudness did not differ significantly between both groups. The dimensionality of the data was reduced by means of principal component analysis (PCA), and the largest resulting components were used for clustering the data. The cluster analysis resulted in five clusters with differences in tinnitus pitch, lateralization, hearing thresholds and MML, as well as on age and gender. Clusters differed in contours of hearing thresholds and MML, describing patterns of low or high thresholds in combination with low or high MML. The clustering solution presented a low silhouette value (0.45), implying that the clustering is weak and could be artificial. The analysis pointed out the diversity across tinnitus patients. Our results suggest that there might be a continuum of patients' characteristics rather than discrete subgroups.

Gray matter declines with age and hearing loss, but is partially maintained in tinnitus.

The impact of age-related hearing loss extends beyond the auditory pathway and impacts brain areas related to cognitive impairment and even dementia. The presence of tinnitus, a sensation of sound that frequently co-occurs with hearing loss, is additionally linked to cognitive decline. Interestingly, structural neuroimaging studies have reported that hearing loss may precede or modulate the onset of cognitive impairment. In this study, we aimed to disentangle the effects of age, hearing loss, and tinnitus on gray matter structure. In total, 39 participants with hearing loss and tinnitus, 21 with hearing loss but without tinnitus, and 39 controls were included in this voxel- and surface-based morphometry MRI study. Whole brain volume and surface thickness measures were compared between the groups. Age-related gray matter volume decline was observed in all groups. Several brain areas showed smaller gray matter volume and cortical surface thickness in hearing loss without tinnitus, relative to controls. This reduction was observed both within and outside of the auditory pathway. Interestingly, these reductions were not observed in participants with tinnitus, who had similar hearing loss and were of similar age. Since we have tools to improve hearing loss, hearing screening may aid in the battle against cognitive decline.

Frequency selectivity of tonal language native speakers probed by suppression tuning curves of spontaneous otoacoustic emissions.

Native acquisition of a tonal language (TL) is related to enhanced abilities of pitch perception and production, compared to non-tonal language (NTL) native speakers. Moreover, differences in brain responses to both linguistically relevant and non-relevant pitch changes have been described in TL native speakers. It is so far unclear to which extent differences are present at the peripheral processing level of the cochlea. To determine possible differences in cochlear frequency selectivity between Asian TL speakers and Caucasian NTL speakers, suppression tuning curves (STCs) of spontaneous otoacoustic emissions (SOAEs) were examined in both groups. By presenting pure tones, SOAE levels were suppressed and STCs were derived. SOAEs with center frequencies higher than 4.5 kHz were recorded only in female TL native speakers, which correlated with better high-frequency tone detection thresholds. The suppression thresholds at the tip of the STC and filter quality coefficient Q10dB did not differ significantly between both language groups. Thus, the characteristics of the STCs of SOAEs do not support the presence of differences in peripheral auditory processing between TL and NTL native speakers.

Associations between tinnitus and glaucoma suggest a common mechanism: A clinical and population-based study.

The purpose of this study was to determine if there is an association between tinnitus and glaucoma. We tested this by first completing a clinic-based cross-sectional questionnaire study in which we sent a series of tinnitus-related questions to glaucoma patients and healthy subjects, and then followed up with a large population-based cross-sectional study in which glaucoma and tinnitus were also assessed by questionnaire. For the clinical study, we received 209 responses from glaucoma patients and 109 responses from healthy subjects (primarily the spouses of the patients). For the population-based study, we evaluated 79,866 participants. Logistic regression models were used to test the relationship between glaucoma and tinnitus; the clinical study analysis was adjusted for age, gender, BMI, hypertension, and diabetes and the population-based study was adjusted for these same variables with the addition of socioeconomic status and subjective hearing loss. For the clinical study, glaucoma patients had an 85% increase in odds for tinnitus (adjusted OR 1.85, 95% CI 1.10 to 3.05). The effect did not depend on pretreatment intraocular pressure, and the associated symptoms were not pulsatile in nature. For the population-based study, glaucoma patients had a 19% increase in odds for tinnitus (adjusted OR 1.19, 95% CI 1.02 to 1.40). Overall, our results suggest that those with glaucoma are more likely to have tinnitus than those without glaucoma. These results provide hypotheses for a mechanism involved in both tinnitus and glaucoma. One possible mechanism could be vascular dysregulation due to impairment of nitric oxide production.

Suppression tuning of spontaneous otoacoustic emissions in the barn owl (Tyto alba).

Spontaneous otoacoustic emissions (SOAEs) have been observed in a variety of different vertebrates, including humans and barn owls (Tyto alba). The underlying mechanisms producing the SOAEs and the meaning of their characteristics regarding the frequency selectivity of an individual and species are, however, still under debate. In the present study, we measured SOAE spectra in lightly anesthetized barn owls and suppressed their amplitudes by presenting pure tones at different frequencies and sound levels. Suppression effects were quantified by deriving suppression tuning curves (STCs) with a criterion of 2 dB suppression. SOAEs were found in 100% of ears (n = 14), with an average of 12.7 SOAEs per ear. Across the whole SOAE frequency range of 3.4-10.2 kHz, the distances between neighboring SOAEs were relatively uniform, with a median distance of 430 Hz. The majority (87.6%) of SOAEs were recorded at frequencies that fall within the barn owl's auditory fovea (5-10 kHz). The STCs were V-shaped and sharply tuned, similar to STCs from humans and other species. Between 5 and 10 kHz, the median Q10dB value of STC was 4.87 and was thus lower than that of owl single-unit neural data. There was no evidence for secondary STC side lobes, as seen in humans. The best thresholds of the STCs varied from 7.0 to 57.5 dB SPL and correlated with SOAE level, such that smaller SOAEs tended to require a higher sound level to be suppressed. While similar, the frequency-threshold curves of auditory-nerve fibers and STCs of SOAEs differ in some respects in their tuning characteristics indicating that SOAE suppression tuning in the barn owl may not directly reflect neural tuning in primary auditory nerve fibers.

Intraocular and intracranial pressure in glaucoma patients taking acetazolamide.

The alternative mechanical theory of glaucoma, in which an increased pressure difference across the lamina cribrosa (difference between intraocular and intracranial pressure; IOP and ICP), rather than solely an elevated IOP, leads to structural and functional vision loss, is still controversial. If the theory is true, a drug that simultaneously lowers both the IOP and ICP may be ineffective. The aim of this study was to determine how acetazolamide (AAZ; a drug prescribed in glaucoma that aims to lower the IOP) affects both IOP and ICP in glaucoma patients and to compare the magnitude and time course of the induced pressure changes with those of healthy subjects not taking AAZ. IOP and noninvasive ICP (measured through emissions from the ear) were measured in 20 glaucoma patients taking 125 mg of AAZ twice daily. Measurements were taken for 30 minutes before taking the drug and for 2 hours post-ingestion. Comparisons were made with 13 age-similar controls. After 12 hours with no anti-glaucoma medication, AAZ did not further reduce IOP in glaucoma patients compared to controls (P = 0.58) but did reduce ICP compared to controls (P = 0.035), by approximately 4 mmHg. Our findings suggest that there are periods during the day when the pressure difference across the lamina cribrosa is larger in case of AAZ use. Future studies should focus on improving the noninvasive ICP testing, different doses and dosing schedules of AAZ, and the time course of IOP in glaucoma patients not taking AAZ.

Noninvasive intracranial pressure assessment using otoacoustic emissions: An application in glaucoma.

The theory that glaucoma patients have a lower intracranial pressure (ICP) than healthy subjects is a controversial one. The aim of this study was to assess ICP noninvasively by determining the relationship between distortion product otoacoustic emission (DPOAE) phase and body position and to compare this relationship between patients with primary open angle glaucoma (POAG), patients with normal tension glaucoma (NTG), and controls. The relationship was also calibrated using published data regarding invasive measurements of ICP versus body position. DPOAEs were measured in 30 controls and 32 glaucoma patients (17 POAG, 15 NTG) at the following body positions (assuming 90° as upright): 45, 30, 20, 10, 0 (supine), -10, and -20°. DPOAE phase had a clear, nonlinear relationship with body position. The mean DPOAE phase shifts between the two most extreme body positions (45 to -20°) were 73.6, 80.7, and 66.3° for healthy, POAG, and NTG, respectively (P = 0.73), and the groups showed the same, nonlinear behaviour. This indicates that there is no evidence that glaucoma patients have a reduced ICP. When calibrated with invasive data, ICP and DPOAE phase were linearly related over an ICP of 3 mmHg. This suggests that, more broadly, DPOAEs could be used in the future to monitor changes in ICP in a clinical setting and to measure dynamic changes in ICP such as diurnal fluctuations or changes induced by certain medications.

The treatment of idiopathic sudden sensorineural hearing loss using pulse therapy: a prospective, randomized, double-blind clinical trial.

OBJECTIVES: The etiology and treatment of idiopathic sudden sensorineural hearing loss (ISSHL) is still unclear. The anti-inflammatory effect of corticosteroids is thought to play an important part in the recovery from ISSHL. We aimed to determine whether a more powerful anti-inflammatory technique using pulse therapy is effective in the treatment of ISSHL. METHODS: In a randomized, prospective, double-blind, multicenter clinical trial, we recruited 81 patients with ISSHL. Patients were randomly allocated to pulse therapy (300 mg dexamethasone for 3 consecutive days followed by 4 days of placebo) or control treatment (prednisone 70 mg per day tapered in steps of 10 mg per day to 0 mg). The primary outcome was hearing recovery as measured by pure-tone audiometry and speech audiometry after 12 months. Secondary outcomes were subjective parameters such as hearing recovery, tinnitus, vertigo, and a pressure sensation in the ear. RESULTS: The overall improvement in pure-tone thresholds and speech discrimination scores was not significantly better in patients who were given dexamethasone than those who were given standard prednisone. Hearing improved from 71 dB HL to 36 dB HL in the dexamethasone group and from 75 dB HL to 42 dB HL in the prednisone group. Speech discrimination scores of 100% were achieved by 64% of dexamethasone-treated patients and by 57% of the prednisone group. CONCLUSION: Pulse therapy is equally effective and safe as standard-dose prednisone. Pulse therapy suppresses both humoral and cellular immune responses and therefore has a wider anti-inflammatory effect.

Cluster Analysis to Identify Possible Subgroups in Tinnitus Patients.

INTRODUCTION: In tinnitus treatment, there is a tendency to shift from a "one size fits all" to a more individual, patient-tailored approach. Insight in the heterogeneity of the tinnitus spectrum might improve the management of tinnitus patients in terms of choice of treatment and identification of patients with severe mental distress. The goal of this study was to identify subgroups in a large group of tinnitus patients. METHODS: Data were collected from patients with severe tinnitus complaints visiting our tertiary referral tinnitus care group at the University Medical Center Groningen. Patient-reported and physician-reported variables were collected during their visit to our clinic. Cluster analyses were used to characterize subgroups. For the selection of the right variables to enter in the cluster analysis, two approaches were used: (1) variable reduction with principle component analysis and (2) variable selection based on expert opinion. RESULTS: Various variables of 1,783 tinnitus patients were included in the analyses. Cluster analysis (1) included 976 patients and resulted in a four-cluster solution. The effect of external influences was the most discriminative between the groups, or clusters, of patients. The "silhouette measure" of the cluster outcome was low (0.2), indicating a "no substantial" cluster structure. Cluster analysis (2) included 761 patients and resulted in a three-cluster solution, comparable to the first analysis. Again, a "no substantial" cluster structure was found (0.2). CONCLUSION: Two cluster analyses on a large database of tinnitus patients revealed that clusters of patients are mostly formed by a different response of external influences on their disease. However, both cluster outcomes based on this dataset showed a poor stability, suggesting that our tinnitus population comprises a continuum rather than a number of clearly defined subgroups.

Innovations in Doctoral Training and Research on Tinnitus: The European School on Interdisciplinary Tinnitus Research (ESIT) Perspective.

Tinnitus is a common medical condition which interfaces many different disciplines, yet it is not a priority for any individual discipline. A change in its scientific understanding and clinical management requires a shift toward multidisciplinary cooperation, not only in research but also in training. The European School for Interdisciplinary Tinnitus research (ESIT) brings together a unique multidisciplinary consortium of clinical practitioners, academic researchers, commercial partners, patient organizations, and public health experts to conduct innovative research and train the next generation of tinnitus researchers. ESIT supports fundamental science and clinical research projects in order to: (1) advancing new treatment solutions for tinnitus, (2) improving existing treatment paradigms, (3) developing innovative research methods, (4) performing genetic studies on, (5) collecting epidemiological data to create new knowledge about prevalence and risk factors, (6) establishing a pan-European data resource. All research projects involve inter-sectoral partnerships through practical training, quite unlike anything that can be offered by any single university alone. Likewise, the postgraduate training curriculum fosters a deep knowledge about tinnitus whilst nurturing transferable competencies in personal qualities and approaches needed to be an effective researcher, knowledge of the standards, requirements and professionalism to do research, and skills to work with others and to ensure the wider impact of research. ESIT is the seed for future generations of creative, entrepreneurial, and innovative researchers, trained to master the upcoming challenges in the tinnitus field, to implement sustained changes in prevention and clinical management of tinnitus, and to shape doctoral education in tinnitus for the future.

Detection of intracochlear and intracranial pressure changes with otoacoustic emissions: a gerbil model.

Increased intracranial pressure (ICP) is known to affect the phases and levels of lower-frequency distortion-product otoacoustic emissions (DPOAE) in a characteristic manner suggestive of an increase in the stiffness of the stapes system, likely in relation to an attendant increased intracochlear pressure (ICoP). DPOAEs may thus provide an easy non-invasive means of gaining access to the otherwise elusive ICoP. However, the mechanisms by which DPOAEs actually relate to ICoP are unclear and may involve changes in the stiffness of the annular ligament, stapedius muscle and even some indirect contributions of other parts of the middle ear such as the tensor tympani. A systematic study of the role of each middle-ear element on ICoP-to-DPOAE relationships as a function of frequency was undertaken in gerbils under direct control of ICP via an intracranial catheter (from 0 to 500 daPa). After the bulla was widely opened, the tendons of the stapedius and tensor tympani muscles were severed in turn. A standard electroacoustic analog model of the middle ear was used for predicting the forward and reverse middle-ear transfer-functions changes under different experimental manipulations and their consequences on DPOAEs. The observed DPOAE changes chiefly consisted in a phase-lead peaking around 2.15 kHz in closed-bulla, and 1.2 kHz in open-bulla conditions. It was proportional to ICP increase provided ICP exceeded a threshold of about 50 daPa. The profiles of DPOAE shifts matched those derived from the premise that ICoP mainly induced a change in the stiffness of the stapes system. The possible involvement of the stapedius muscle was ruled out by the absence of any effect of cutting its tendon so that the intrinsically non-linear stiffness of the annular ligament must have been the main factor. A relatively minor contribution from the tensor tympani was observed, possibly in relation to the detection of ICoP-induced displacement of the ossicular chain by neuromuscular spindles.