The Origin Along the Cochlea of Otoacoustic Emissions Evoked by Mid-Frequency Tone Pips.

PURPOSE: Tone-pip-evoked otoacoustic emissions (PEOAEs) are transient-evoked otoacoustic emissions (OAEs) that are hypothesized to originate from reflection of energy near the best-frequency (BF) cochlear place of the stimulus frequency. However, individual PEOAEs have energy with a wide range of delays. We sought to determine whether some PEOAE energy is consistent with having been generated far from BF. METHODS: PEOAEs from 35 and 47 dB SPL tone pips were obtained by removing pip-stimulus energy by subtracting the ear-canal sound pressure from scaled-down 59 dB SPL tone pips (which evoke relatively small OAEs). PEOAE delays were measured at each peak in the PEOAE absolute-value waveforms. While measuring PEOAEs and auditory-nerve compound action potentials (CAPs), amplification was blocked sequentially from apex to base by cochlear salicylate perfusion. The perfusion time when a CAP was reduced identified when the perfusion reached the tone-pip BF place. The perfusion times when each PEOAE peak was reduced identified where along the cochlea it received cochlear amplification. PEOAEs and CAPs were measured simultaneously using one pip frequency in each ear (1.4 to 4 kHz across 16 ears). RESULTS: Most PEOAE peaks received amplification primarily between the BF place and 1-2 octaves basal of the BF place. PEOAE peaks with short delays received amplification basal of BF place. PEOAE peaks with longer delays sometimes received amplification apical of BF place, consistent with previous stimulus-frequency-OAE results. CONCLUSION: PEOAEs provide information about cochlear amplification primarily within ~ 1.5 octave of the tone-pip BF place, not about regions > 3 octaves basal of BF.

The Rhode non-linearity and its impact on cochlear mechanics.

The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.

Measurements From Ears With Endolymphatic Hydrops and 2-Hydroxypropyl-Beta-Cyclodextrin Provide Evidence That Loudness Recruitment Can Have a Cochlear Origin.

Background: Loudness recruitment is commonly experienced by patients with putative endolymphatic hydrops. Loudness recruitment is abnormal loudness growth with high-level sounds being perceived as having normal loudness even though hearing thresholds are elevated. The traditional interpretation of recruitment is that cochlear amplification has been reduced. Since the cochlear amplifier acts primarily at low sound levels, an ear with elevated thresholds from reduced cochlear amplification can have normal processing at high sound levels. In humans, recruitment can be studied using perceptual loudness but in animals physiological measurements are used. Recruitment in animal auditory-nerve responses has never been unequivocally demonstrated because the animals used had damage to sensory and neural cells, not solely a reduction of cochlear amplification. Investigators have thus looked for, and found, evidence of recruitment in the auditory central nervous system (CNS). While studies on CNS recruitment are informative, they cannot rule out the traditional interpretation of recruitment originating in the cochlea. Design: We used techniques that could assess hearing function throughout entire frequency- and dynamic-range of hearing. Measurements were made from two animal models: guinea-pig ears with endolymphatic-sac-ablation surgery to produce endolymphatic hydrops, and naïve guinea-pig ears with cochlear perfusions of 13 mM 2-Hydroxypropyl-Beta-Cyclodextrin (HPBCD) in artificial perilymph. Endolymphatic sac ablation caused low-frequency loss. Animals treated with HPBCD had hearing loss at all frequencies. None of these animals had loss of hair cells or synapses on auditory nerve fibers. Results: In ears with endolymphatic hydrops and those perfused with HPBCD, auditory-nerve based measurements at low frequencies showed recruitment compared to controls. Recruitment was not found at high frequencies (> 4 kHz) where hearing thresholds were normal in ears with endolymphatic hydrops and elevated in ears treated with HPBCD. Conclusions: We found compelling evidence of recruitment in auditory-nerve data. Such clear evidence has never been shown before. Our findings suggest that, in patients suspected of having endolymphatic hydrops, loudness recruitment may be a good indication that the associated low-frequency hearing loss originates from a reduction of cochlear amplification, and that measurements of recruitment could be used in differential diagnosis and treatment monitoring of Ménière's disease.

Optimized Diagnostic Approach to Patients Suspected of Superior Semicircular Canal Dehiscence.

OBJECTIVES: Current methods of diagnosing superior semicircular canal dehiscence syndrome (SCDS) include a clinical exam, audiometric testing, temporal bone computer tomography (CT) imaging, and vestibular evoked myogenic potential (VEMP) testing. The main objective of this study was to develop an improved diagnostic approach to SCDS optimized for accuracy, efficiency, and safety that utilizes clinical presentation, audiometric testing, CT imaging, high-frequency cervical VEMP (cVEMP) testing, and patient treatment preference. A secondary aim was to investigate the cost associated with the current versus proposed diagnostic paradigms. DESIGN: All patients who underwent cVEMP testing since introduction of the 2 kHz cVEMP in our clinical protocol in July 2018 were screened. Patients suspected of SCDS based upon symptoms who also had available audiogram, CT scan, and 2 kHz cVEMP were included (58 ears). Patients were categorized as dehiscent, thin, or not dehiscent based on their CT scan. Symptom prevalence and cVEMP outcomes were analyzed and compared for all groups. The accuracy of the 2 kHz cVEMP was calculated using CT imaging as the standard. Using a combination of patient symptomatology, audiometric, CT and 2 kHz cVEMP data, as well as patient preference, a best clinical practice approach was developed. The cost associated with this approach was calculated and compared with cost of the current SCDS diagnostic workup using Medicare reimbursement rates. RESULTS: In the overall patient population suspected of SCDS based on clinical presentation, the sensitivity and specificity of 2 kHz cVEMP were 76% and 100%, respectively, while the positive and negative predictive values were 100% and 84.6%, assuming that the CT scan finding was correct. Autophony was the most common symptom in patients who had both superior semicircular canal dehiscence on CT imaging plus abnormal 2 kHz cVEMP (p < 0.001). Combining patient symptomatology, 2 kHz normalized peak to peak cVEMP amplitude, and patient treatment preference to determine, which patients should undergo CT scanning resulted in a potential cost reduction between 45% and 61%. CONCLUSION: In patients suspected of SCDS based on their clinical presentation, the combination of symptomatology, 2 kHz cVEMP data, and patient preference can be used to determine which patients should undergo CT scanning, resulting in a diagnostic cost reduction and reduced patient radiation exposure.

The interplay of organ-of-Corti vibrational modes, not tectorial- membrane resonance, sets outer-hair-cell stereocilia phase to produce cochlear amplification.

The mechanical motions that deflect outer-hair-cell (OHC) stereocilia and the resulting effects of OHC motility are reviewed, concentrating on high-frequency cochlear regions. It has been proposed that a tectorial-membrane (TM) resonance makes the phase of OHC stereocilia motion be appropriate to produce cochlear amplification, i.e. so that the OHC force that pushes the basilar membrane (BM) is in the same direction as BM velocity. Evidence for and against the TM-resonance hypothesis are considered, including new cochlear-motion measurements using optical coherence tomography, and it is concluded that there is no such TM resonance. The evidence points to there being an advance in the phase of reticular lamina (RL) radial motion at a frequency approximately ½ octave below the BM characteristic frequency, and that this is the main source of the phase difference between the TM and RL radial motions that produces cochlear amplification. It appears that the change in phase of RL radial motion comes about because of a transition between different organ-of-Corti (OoC) vibrational modes that changes RL motion relative to BM and TM motion. The origins and consequences of the large phase change of RL radial motion relative to BM motion are considered; differences in the reported patterns of these changes may be due to different viewing angles. Detailed motion data and new models are needed to better specify the vibrational patterns of the OoC modes and the role of the various OoC structures in producing the modes and the mode transition.

Anatomy of the Human Osseous Spiral Lamina and Cochlear Partition Bridge: Relevance for Cochlear Partition Motion.

The classic view of cochlear partition (CP) motion, generalized to be for all mammals, was derived from basal-turn measurements in laboratory animals. Recently, we reported motion of the human CP in the cochlear base that differs substantially from the classic view. We described a human soft tissue "bridge" (non-existent in the classic view) between the osseous spiral lamina (OSL) and basilar membrane (BM), and showed how OSL and bridge move in response to sound. Here, we detail relevant human anatomy to better understand the relationship between form and function. The bridge and BM have similar widths that increase linearly from base to apex, whereas the OSL width decreases from base to apex, leading to an approximately constant total CP width throughout the cochlea. The bony three-dimensional OSL microstructure, reconstructed from unconventionally thin, 2-µm histological sections, revealed thin, radially wide OSL plates with pores that vary in size, extent, and distribution with cochlear location. Polarized light microscopy revealed collagen fibers in the BM that spread out medially through the bridge to connect to the OSL. The long width and porosity of the OSL may explain its considerable bending flexibility. The similarity of BM and bridge widths along the cochlea, both containing continuous collagen fibers, may make them a functional unit and allow maximum CP motion near the bridge-BM boundary, as recently described. These anatomical findings may help us better understand the motion of the structures surrounding the organ of Corti and how they shape the input to the cochlear sensory mechanism.

The Spatial Origins of Cochlear Amplification Assessed by Stimulus-Frequency Otoacoustic Emissions.

Cochlear amplification of basilar membrane traveling waves is thought to occur between a tone's characteristic frequency (CF) place and within one octave basal of the CF. Evidence for this view comes only from the cochlear base. Stimulus-frequency otoacoustic emissions (SFOAEs) provide a noninvasive alternative to direct measurements of cochlear motion that can be measured across a wide range of CF regions. Coherent reflection theory indicates that SFOAEs arise mostly from the peak region of the traveling wave, but several studies using far-basal suppressor tones claimed that SFOAE components originate many octaves basal of CF. We measured SFOAEs while perfusing guinea pig cochleas from apex to base with salicylate or KCl solutions that reduced outer-hair-cell function and SFOAE amplification. Solution effects on inner hair cells reduced auditory nerve compound action potentials (CAPs) and provided reference times for when solutions reached the SFOAE-frequency CF region. As solution flowed from apex to base, SFOAE reductions generally occurred later than CAP reductions and showed that the effects of cochlear amplification usually peaked ∼1/2 octave basal of the CF region. For tones ≥2 kHz, cochlear amplification typically extended ∼1.5 octaves basal of CF, and the data are consistent with coherent reflection theory. SFOAE amplification did not extend to the basal end of the cochlea, even though reticular lamina motion is amplified in this region, which indicates that reticular lamina motion is not directly coupled to basilar membrane traveling waves. Previous reports of SFOAE-frequency residuals produced by suppressor frequencies far above the SFOAE frequency are most likely due to additional sources created by the suppressor. For some tones <2 kHz, SFOAE amplification extended two octaves apical of CF, which highlights that different vibratory motions produce SFOAEs and CAPs, and that the amplification region depends on the cochlear mode of motion considered. The concept that there is a single "cochlear amplification region" needs to be revised.

Predicting Development of Bilateral Menière's Disease Based on cVEMP Threshold and Tuning.

OBJECTIVE: To investigate if the cervical vestibular evoked myogenic potential (cVEMP) is predictive for developing bilateral Menière's disease (MD). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: Records of 71 patients previously diagnosed with unilateral MD at our institution who underwent cVEMP testing between 2002 and 2011 were screened. INTERVENTION: Patients were contacted to answer a questionnaire to identify which patients had developed bilateral disease. Based on questionnaires and medical charts, 49 patients with a follow-up time of at least 5 years were included. The 49 originally asymptomatic ears are referred to as "study ears." Previously reported cVEMP criteria (original criteria) applied to study-ear cVEMPs separated them into Menière-like and normal-like groups. MAIN OUTCOME MEASURE: The main purpose was to determine if previously obtained cVEMP thresholds and tuning ratios of unilateral MD patients could predict who develops bilateral disease. RESULTS: From the 49 included patients, 12 developed bilateral disease (24.5%). The study ears characterized by original cVEMP criteria as Menière-like were significantly more likely to develop bilateral disease compared with the normal-like study ears. The original criteria predicted development of bilateral disease with a positive predictive value (PPV) and negative predictive value (NPV) of 58.3% and 86.5% respectively. ROC curves were used to revise cVEMP criteria for predicting the progression to bilateral disease. A revised criterion combining three cVEMP metrics, reached a PPV and NPV of 85.7% and 93.7%. CONCLUSION: cVEMP threshold and tuning in unilateral MD patients are predictive of which patients will develop bilateral disease.

Cochlear partition anatomy and motion in humans differ from the classic view of mammals.

Mammals detect sound through mechanosensitive cells of the cochlear organ of Corti that rest on the basilar membrane (BM). Motions of the BM and organ of Corti have been studied at the cochlear base in various laboratory animals, and the assumption has been that the cochleas of all mammals work similarly. In the classic view, the BM attaches to a stationary osseous spiral lamina (OSL), the tectorial membrane (TM) attaches to the limbus above the stationary OSL, and the BM is the major moving element, with a peak displacement near its center. Here, we measured the motion and studied the anatomy of the human cochlear partition (CP) at the cochlear base of fresh human cadaveric specimens. Unlike the classic view, we identified a soft-tissue structure between the BM and OSL in humans, which we name the CP "bridge." We measured CP transverse motion in humans and found that the OSL moved like a plate hinged near the modiolus, with motion increasing from the modiolus to the bridge. The bridge moved almost as much as the BM, with the maximum CP motion near the bridge-BM connection. BM motion accounts for 100% of CP volume displacement in the classic view, but accounts for only 27 to 43% in the base of humans. In humans, the TM-limbus attachment is above the moving bridge, not above a fixed structure. These results challenge long-held assumptions about cochlear mechanics in humans. In addition, animal apical anatomy (in SI Appendix) doesn't always fit the classic view.

Cervical Vestibular Evoked Myogenic Potentials in Menière's Disease: A Comparison of Response Metrics.

OBJECTIVE: The cervical vestibular evoked myogenic potential (cVEMP) has been used to evaluate patients with Menière's disease (MD). Studied cVEMP metrics include: amplitude, threshold, frequency tuning, and interaural asymmetry ratio (IAR). However, few studies compared these metrics in the same set of MD patients, and methodological differences prevent such a comparison across studies. This study investigates the value of different cVEMP metrics in distinguishing one set of MD patients from age-matched controls. STUDY DESIGN: Prospective study. SETTING: Tertiary care center. PATIENTS: Thirty patients with definite unilateral MD and 23 age-matched controls were prospectively included. All underwent cVEMP testing at 500, 750, 1000, and 2000 Hz on each side. Ears were separated into three groups: affected MD, unaffected MD, and control. MAIN OUTCOME MEASURES: Sound level functions were obtained at each frequency, and normalized peak-to-peak amplitude (VEMPn), VEMP inhibition depth (VEMPid), threshold, frequency-tuning ratio, and IAR were calculated. For all metrics, the differentiation between MD and control ears was compared using receiver operating characteristic (ROC) curves. RESULTS: 500 Hz cVEMP threshold, VEMPn, and VEMPid were similarly good at distinguishing affected MD ears from healthy ears, with ROC area under the curves (AUCs) of more than 0.828 and optimal sensitivities and specificities of at least 80 and 70%. Combinations of these three metrics yielded slightly larger AUCs (>0.880). Tuning ratios and IAR were less effective in separating healthy from affected ears with AUCs ranging from 0.529 to 0.720. CONCLUSION: The cVEMP metrics most useful in distinguishing MD patients from healthy controls are threshold, VEMPn, and VEMPid, using 500 Hz stimuli.

Normalizing cVEMPs: Which Method Is the Most Effective?

OBJECTIVES: To determine the most effective method for normalizing cervical vestibular evoked myogenic potentials (cVEMPs). DESIGN: cVEMP data from 20 subjects with normal hearing and vestibular function were normalized using 16 combinations of methods, each using one of the 4 modes of electromyogram (EMG) quantification described below. All methods used the peak to peak value of an averaged cVEMP waveform (VEMPpp) and obtained a normalized cVEMP by dividing VEMPpp by a measure of the EMG amplitude. EMG metrics were obtained from the EMG within short- and long-duration time windows. EMG amplitude was quantified by its root-mean-square (RMS) or average full-wave-rectified (RECT) value. The EMG amplitude was used by (a) dividing each individual trace by the EMG of this specific trace, (b) dividing VEMPpp by the average RMS or RECT of the individual trace EMG, (c) dividing the VEMPpp by an EMG metric obtained from the average cVEMP waveform, or (d) dividing the VEMPpp by an EMG metric obtained from an average cVEMP "noise" waveform. Normalization methods were compared by the normalized cVEMP coefficient of variation across subjects and by the area under the curve from a receiver-operating-characteristic analysis. A separate analysis of the effect of EMG-window duration was done. RESULTS: There were large disparities in the results from different normalization methods. The best methods used EMG metrics from individual-trace EMG measurements, not from part of the average cVEMP waveform. EMG quantification by RMS or RECT produced similar results. For most EMG quantifications, longer window durations were better in producing receiver-operating-characteristic with high areas under the curve. However, even short window durations worked well when the EMG metric was calculated from the average RMS or RECT of the individual-trace EMGs. Calculating the EMG from a long-duration window of a cVEMP "noise" average waveform was almost as good as the individual-trace-EMG methods. CONCLUSIONS: The best cVEMP normalizations use EMG quantification from individual-trace EMGs. To have the normalized cVEMPs accurately reflect the vestibular activation, a good normalization method needs to be used.

Auditory Attention Reduced Ear-Canal Noise in Humans by Reducing Subject Motion, Not by Medial Olivocochlear Efferent Inhibition: Implications for Measuring Otoacoustic Emissions During a Behavioral Task.

Otoacoustic emissions (OAEs) are often measured to non-invasively determine activation of medial olivocochlear (MOC) efferents in humans. Usually these experiments assume that ear-canal noise remains constant. However, changes in ear-canal noise have been reported in some behavioral experiments. We studied the variability of ear-canal noise in eight subjects who performed a two-interval-forced-choice (2IFC) sound-level-discrimination task on monaural tone pips in masker noise. Ear-canal noise was recorded directly from the unstimulated ear opposite the task ear. Recordings were also made with similar sounds presented, but no task done. In task trials, ear-canal noise was reduced at the time the subject did the discrimination, relative to the ear-canal noise level earlier in the trial. In two subjects, there was a decrease in ear-canal noise, primarily at 1-2 kHz, with a time course similar to that expected from inhibition by MOC activity elicited by the task-ear masker noise. These were the only subjects with spontaneous OAEs (SOAEs). We hypothesize that the SOAEs were inhibited by MOC activity elicited by the task-ear masker. Based on the standard rationale in OAE experiments that large bursts of ear-canal noise are artifacts due to subject movement, ear-canal noise bursts above a sound-level criterion were removed. As the criterion was lowered and more high- and moderate-level ear-canal noise bursts were removed, the reduction in ear-canal noise level at the time of the 2IFC discrimination decreased to almost zero, for the six subjects without SOAEs. This pattern is opposite that expected from MOC-induced inhibition (which is greater on lower-level sounds), but can be explained by the hypothesis that subjects move less and create fewer bursts of ear-canal noise when they concentrate on doing the task. In no-task trials for these six subjects, the ear-canal noise level was little changed throughout the trial. Our results show that measurements of MOC effects on OAEs must measure and account for changes in ear-canal noise, especially in behavioral experiments. The results also provide a novel way of showing the time course of the buildup of attention via the time course of the reduction in ear-canal noise.

Audiometric and cVEMP Thresholds Show Little Correlation With Symptoms in Superior Semicircular Canal Dehiscence Syndrome.

OBJECTIVE: Evaluate the relationship between objective audiometric and vestibular tests and patient symptoms in superior canal dehiscence (SCD) syndrome. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care center. PATIENTS: Ninety-eight patients with SCD, preoperative threshold audiograms, cervical vestibular evoked myogenic potential (cVEMP) thresholds, and computed tomography (CT) imaging were included. Clinical reports were reviewed for self-reported SCD symptoms. Twenty-five patients completed the Hearing Handicap Inventory (HHI), Dizziness Handicap Inventory (DHI), Autophony Index (AI), and the 36-item Short Form Survey (SF-36). MAIN OUTCOME MEASURES: Correlations between preoperative low-frequency air-bone gap (ABG), cVEMP thresholds, and symptoms (including HHI, DHI, AI, and SF-36). Symptoms included hearing loss, aural fullness, autophony, hyperacusis, tinnitus, vertigo, imbalance and sound-, pressure and exercise provoked dizziness. Secondary outcome measure: Correlations between changes of objective and subjective measures before and after surgery. RESULTS: Patients who reported hearing loss had larger ABGs at 250 Hz than patients without subjective hearing loss (p = 0.001). ABGs and cVEMP thresholds did not correlate with any other symptom. No significant correlation was found between ABG or cVEMP threshold and the HHI, DHI, AI or Health Utility Value (derived from the SF-36 quality of life score). Following SCD surgery, ABG decreased (p < 0.001), cVEMP thresholds increased (p < 0.001) and overall symptoms, handicap scores and quality-of-life improved; however, there was no significant relationship between these measures. CONCLUSION: While threshold audiometry and cVEMP are important tools to diagnose SCD and monitor surgical outcomes, these measures showed no significant correlation with vestibular and most auditory symptoms or their severity.

Toward Optimizing VEMP: Calculating VEMP Inhibition Depth With a Generic Template.

OBJECTIVES: Cervical vestibular evoked myogenic potentials (cVEMP) indirectly reveal the response of the saccule to acoustic stimuli through the inhibition of sternocleidomastoid muscle electromyographic response. VEMP inhibition depth (VEMPid) is a recently developed metric that estimates the percentage of saccular inhibition. VEMPid provides both normalization and better accuracy at low response levels than amplitude-normalized cVEMPs. Hopefully, VEMPid will aid in the clinical assessment of patients with vestibulopatholgy. To calculate VEMPid a template is needed. In the original method, a subject's own cVEMP was used as the template, but this method can be problematic in patients who do not have robust cVEMP responses. We hypothesize that a "generic" template, created by assembling cVEMPs from healthy subjects, can be used to compute VEMPid, which would facilitate the use of VEMPid in subjects with pathological conditions. DESIGN: A generic template was created by averaging cVEMP responses from 6 normal subjects. To compare VEMPid calculations using a generic versus a subject-specific template, cVEMPs were obtained in 40 healthy subjects using 500, 750, and 1000 Hz tonebursts at sound levels ranging from 98 to 123 dB peSPL. VEMPids were calculated both with the generic template and with the subject's own template. The ability of both templates to determine whether a cVEMP was present or not was compared with receiver operating characteristic curves. RESULTS: No significant differences were found between VEMPid calculations using a generic template versus using a subject-specific template for all frequencies and sound levels. Based on the receiver operating characteristic curves, the subject-specific and generic template did an equally good job at determining threshold. Within limits, the shape of the generic template did not affect these results. CONCLUSIONS: A generic template can be used instead of a subject-specific template to calculate VEMPid. Compared with cVEMP normalized by electromyographic amplitudes, VEMPid is advantageous because it averages zero when there is no sound stimulus and it allows the accumulating VEMPid value to be shown during data acquisition as a guide to deciding when enough data has been collected.

Olivocochlear efferents: Their action, effects, measurement and uses, and the impact of the new conception of cochlear mechanical responses.

The anatomy and physiology of olivocochlear (OC) efferents are reviewed. To help interpret these, recent advances in cochlear mechanics are also reviewed. Lateral OC (LOC) efferents innervate primary auditory-nerve (AN) fiber dendrites. The most important LOC function may be to reduce auditory neuropathy. Medial OC (MOC) efferents innervate the outer hair cells (OHCs) and act to turn down the gain of cochlear amplification. Cochlear amplification had been thought to act only through basilar membrane (BM) motion, but recent reports show that motion near the reticular lamina (RL) is amplified more than BM motion, and that RL-motion amplification extends to several octaves below the local characteristic frequency. Data on efferent effects on AN-fiber responses, otoacoustic emissions (OAEs) and human psychophysics are reviewed and reinterpreted in the light of the new cochlear-mechanical data. The possible origin of OAEs in RL motion is considered. MOC-effect measuring methods and MOC-induced changes in human responses are also reviewed, including that ipsilateral and contralateral sound can produce MOC effects with different patterns across frequency. MOC efferents help to reduce damage due to acoustic trauma. Many, but not all, reports show that subjects with stronger contralaterally-evoked MOC effects have better ability to detect signals (e.g. speech) in noise, and that MOC effects can be modulated by attention.

Non-tip auditory-nerve responses that are suppressed by low-frequency bias tones originate from reticular lamina motion.

Recent cochlear mechanical measurements show that active processes increase the motion response of the reticular lamina (RL) at frequencies more than an octave below the local characteristic frequency (CF) for CFs above 5 kHz. A possible correlate is that in high-CF (>5 kHz) auditory-nerve (AN) fibers, responses to frequencies 1-3 octaves below CF ("tail" frequencies) can be inhibited by medial olivocochlear (MOC) efferents. These results indicate that active processes enhance the sensitivity of tail-frequency RL and AN responses. Perhaps related is that some apical low-CF AN fibers have tuning-curve (TC) "side-lobe" response areas at frequencies above and below the TC-tip that are MOC inhibited. We hypothesized that the tail and side-lobe responses are enhanced by the same active mechanisms as CF cochlear amplification. If responses to CF, tail-frequency, and TC-side-lobe tones are all enhanced by prestin motility controlled by outer-hair-cell (OHC) transmembrane voltage, then they should depend on OHC stereocilia position in the same way. To test this, we cyclically changed the OHC-stereocilia mechano-electric-transduction (MET) operating point with low-frequency "bias" tones (BTs) and increased the BT level until the BT caused quasi-static OHC MET saturation that reduced or "suppressed" the gain of OHC active processes. While measuring cat AN-fiber responses, 50 Hz BT level series, 70-120 dB SPL, were run alone and with CF tones, or 2.5 kHz tail-frequency tones, or side-lobe tones. BT-tone-alone responses were used to exclude BT sound levels that produced AN responses that might obscure BT suppression. Data were analyzed to show the BT phase that suppressed the tone responses at the lowest sound level. We found that AN responses to CF, tail-frequency, and side-lobe tones were suppressed at the same BT phase in almost all cases. The data are consistent with the enhancement of responses to CF, tail-frequency, and side-lobe tones all being due to the same OHC-stereocilia MET-dependent active process. Thus, OHC active processes enhance AN responses at frequencies outside of the cochlear-amplified TC-tip region in both high- and low-frequency cochlear regions. The data are consistent with the AN response enhancements being due to enhanced RL motion that drives IHC-stereocilia deflection by traditional RL-TM shear and/or by changing the RL-TM gap. Since tail-frequency basilar membrane (BM) motion is not actively enhanced, the tail-frequency IHC drive is from a vibrational mode little present on the BM, not a "second filter" of BM motion.

Toward Optimizing Cervical Vestibular Evoked Myogenic Potentials (cVEMP): Combining Air-Bone Gap and cVEMP Thresholds to Improve Diagnosis of Superior Canal Dehiscence.

OBJECTIVE: To develop a novel approach combining low-frequency air-bone gap (ABG) and cervical vestibular evoked myogenic potential (cVEMP) thresholds to improve screening for superior canal dehiscence (SCD) syndrome. STUDY DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: One hundred forty patients with SCD and 21 healthy age-matched controls were included. Ears for each patient were divided into three groups based on computed tomography (CT) findings: 1) dehiscent, 2) thin, or 3) unaffected. MAIN OUTCOME MEASURES: cVEMP and audiometric thresholds were analyzed and differences among groups were evaluated. RESULTS: We define the third window indicator (TWI) as the cVEMP thresholds at 500, 750, and 1000 Hz adjusted for the ABG at 250 Hz (i.e., subtracting ABG from cVEMP threshold). The TWI differentiates between dehiscent and nondehiscent control ears with a sensitivity of 82% and specificity of 100%, corresponding to a positive predictive value of 100%. ABGs and cVEMP thresholds were similar for healthy controls and patients with thin bone over the superior canal. CONCLUSION: This is the largest study to date examining the usefulness of cVEMPs in the diagnosis of SCD. Our "third window indicator" (TWI) combines cVEMP thresholds with the ABG at 250 Hz to improve the ability to screen patients with SCD symptoms.

Toward Optimizing cVEMP: 2,000-Hz Tone Bursts Improve the Detection of Superior Canal Dehiscence.

BACKGROUND: The cervical vestibular evoked myogenic potential (cVEMP) test measures saccular and inferior vestibular nerve function. The cVEMP can be elicited with different frequency stimuli and interpreted using a variety of metrics. Patients with superior semicircular canal dehiscence (SCD) syndrome generally have lower cVEMP thresholds and larger amplitudes, although there is overlap with healthy subjects. The aim of this study was to evaluate which metric and frequency best differentiate healthy ears from SCD ears using cVEMP. METHODS: Twenty-one patients with SCD and 23 age-matched controls were prospectively included and underwent cVEMP testing at 500, 750, 1,000 and 2,000 Hz. Sound level functions were obtained at all frequencies to acquire threshold and to calculate normalized peak-to-peak amplitude (VEMPn) and VEMP inhibition depth (VEMPid). Third window indicator (TWI) metrics were calculated by subtracting the 250-Hz air-bone gap from the ipsilateral cVEMP threshold at each frequency. Ears of SCD patients were divided into three groups based on CT imaging: dehiscent, thin or unaffected. The ears of healthy age-matched control subjects constituted a fourth group. RESULTS: Comparing metrics at all frequencies revealed that 2,000-Hz stimuli were most effective in differentiating SCD from normal ears. ROC analysis indicated that for both 2,000-Hz cVEMP threshold and for 2,000-Hz TWI, 100% specificity could be achieved with a sensitivity of 92.0%. With 2,000-Hz VEMPn and VEMPid at the highest sound level, 100% specificity could be achieved with a sensitivity of 96.0%. CONCLUSION: The best diagnostic accuracy of cVEMP in SCD patients can be achieved with 2,000-Hz tone burst stimuli, regardless of which metric is used.

Efferent inhibition strength is a physiological correlate of hyperacusis in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is a developmental disability that is poorly understood. ASD can influence communication, social interaction, and behavior. Children with ASD often have sensory hypersensitivities, including auditory hypersensitivity (hyperacusis). In adults with hyperacusis who are otherwise neurotypical, the medial olivocochlear (MOC) efferent reflex is stronger than usual. In children with ASD, the MOC reflex has been measured, but without also assessing hyperacusis. We assessed the MOC reflex in children with ASD by measuring the strength of MOC-induced inhibition of transient-evoked otoacoustic emissions (TEOAEs), a noninvasive physiological measure that reflects cochlear amplification. MOC activity was evoked by contralateral noise. Hyperacusis was assessed subjectively on the basis of the children's symptoms. We found a significant correlation between hyperacusis scores and MOC strength in children with ASD. When children were divided into ASD-with-severe-hyperacusis (ASDs), ASD-with-not-severe-hyperacusis (ASDns), and neurotypical (NT) groups, the last two groups had similar hyperacusis and MOC reflexes, whereas the ASDs group, on average, had hyperacusis and MOC reflexes that were approximately twice as strong. The MOC inhibition of TEOAEs averaged larger at all frequencies in the ASDs compared with ASDns and NT groups. The results suggest that the MOC reflex can be used to estimate hyperacusis in children with ASD and might be used to validate future questionnaires to assess hyperacusis. Our results also provide evidence that strong MOC reflexes in children with ASD are associated with hyperacusis and that hyperacusis is a comorbid condition and is not a necessary, integral part of the abnormal neural processing associated with ASD.NEW & NOTEWORTHY Children with autism spectrum disorder (ASD) are a heterogeneous group, some with hyperacusis and some without. Our research shows that hyperacusis can be estimated in children with ASD by using medial olivocochlear (MOC) reflex measurements. By establishing that an objective measure correlates with attributes of hyperacusis, our results enable future work to enable subtyping of children with ASD to provide improved individualized treatments to at-risk children and those without adequate language to describe their hyperacusis symptoms.