Preventing presbycusis in mice with enhanced medial olivocochlear feedback.

"Growing old" is the most common cause of hearing loss. Age-related hearing loss (ARHL) (presbycusis) first affects the ability to understand speech in background noise, even when auditory thresholds in quiet are normal. It has been suggested that cochlear denervation ("synaptopathy") is an early contributor to age-related auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics ("gain of function" nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calcium-gated potassium channels. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses. Cochlear structure was characterized in immunolabeled organ of Corti whole mounts using confocal microscopy to quantify hair cells, auditory neurons, presynaptic ribbons, and postsynaptic glutamate receptors. Aged wild-type mice had elevated acoustic thresholds and synaptic loss. Afferent synapses were lost from inner hair cells throughout the aged cochlea, together with some loss of outer hair cells. In contrast, cochlear structure and function were preserved in aged mice with gain-of-function nAChRs that provide enhanced olivocochlear inhibition, suggesting that efferent feedback is important for long-term maintenance of inner ear function. Our work provides evidence that olivocochlear-mediated resistance to presbycusis-ARHL occurs via the α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.

Role of the medial olivocochlear efferent auditory system in speech perception in noise: a systematic review and meta-analyses.

OBJECTIVE: The study investigated the relationship between the strength of the medial olivocochlear reflex (measured via contralateral inhibition of otoacoustic emissions) and speech perception in noise (obtained from behavioural identification task) through meta-analyses. DESIGN: A systematic review and random-effects meta-analysis of studies investigating the relationship in neurotypical adults was performed. STUDY SAMPLE: The systematic search (in PubMed, Scopus, Science Direct and Google Scholar databases) revealed 21 eligible studies, which were critically appraised using the NIH tool for Observational Cohort and Cross-Sectional Studies. Meta-analysis was performed on 17 studies (374 participants) with fair to good quality. RESULTS: The results revealed that the medial olivocochlear reflex accounts for less than 1% of the variations in speech perception in noise in neurotypical individuals. Sub-group analyses conducted to address a few methodological differences also revealed no discernible association between the two variables. CONCLUSIONS: The results reveal no modulatory effect of the medial olivocochlear reflex assessed using contralateral inhibition of otoacoustic emission on the ability to perceive speech in noise. However, more data utilising alternative measures of medial olivocochlear reflex strength is necessary before drawing any conclusions about the role of the medial olivocochlear bundle in speech perception in noise.

Magnitude of medial olivocochlear reflex assayed by tone-burst-evoked otoacoustic emissions: reliability and comparison with click-evoked emissions.

OBJECTIVE: The purpose of this pilot study was to evaluate the magnitude of the medial olivocochlear reflex (MOCR) estimated by the reduction in tone-burst evoked otoacoustic emissions (TBOAEs) measured at three levels and at three frequencies in response to fixed contralateral white noise. Results were compared with commonly used click-evoked otoacoustic emissions (CEOAEs). DESIGN: TBOAEs and CEOAEs, with and without contralateral 60 dB SPL white noise, were measured in response to stimulation at 55, 65, and 75 dB peSPL. In each subject, the set of measurements was performed twice. Of particular interest were the MOCR and its repeatability. STUDY SAMPLE: 15 normally hearing persons (13 women, average age 32.3 years, SD = 8.1). RESULTS: For both CEOAE and TBOAEs, the reliability of the MOCR was much better for broadband measurements than for half-octave-band filtered estimates. At the same time, the reliability of MOCR in half-octave bands was higher for TBOAEs than for CEOAEs, especially at 2 and 4 kHz. CONCLUSIONS: For general applications where broadband MOCR is of interest, the highest magnitude and reliability is provided by CEOAEs. However, TBOAEs may be better if a particular frequency band is of interest.

The comprehensive audiological evaluation in young violinists: the medial olivocochlear system, high frequency thresholds, and the auditory figure ground test.

PURPOSE: The aim of this study was to examine whether the medial olivocochlear hearing system functions, the high frequency hearing thresholds and speech discrimination in noise performance can guide us in assessing the risk of hearing loss among violinists. It is aimed to investigate possible hearing damage that is not reflected in pure tone hearing thresholds in violinists. METHODS: The participants (n = 50) who have normal hearing and the ages of 18-30 were included in this study in two groups: violinists and controls who are unrelated to music. High frequency audiometer, auditory figure ground test (AFG) for speech discrimination in noise performance, Distortion Product Otoacoustic Emission (DPOAE) and contralateral suppression on DPOAE for medial olivocochlear system function tests were applied to all participants as well as routine audiological tests. RESULTS: The high frequency hearing thresholds were obtained higher in violinists compared to the controls. In violinists, the AFG test scores and the suppression amount at 1 kHz were lower than the controls. In addition, DPOAE responses at 4-6 kHz were obtained lower in violinists (p < 0.05). CONCLUSION: The reason for high frequency hearing loss, decreased DPOAE response amplitudes, and poor medial olivocochlear function in violinists can be explained by the long-term exposure to high-level noise caused by the violin, one of the closest musical instruments. Routine and comprehensive audiological follow-up is crucial for musicians.

Synaptic Inhibition of Medial Olivocochlear Efferent Neurons by Neurons of the Medial Nucleus of the Trapezoid Body.

Medial olivocochlear (MOC) efferent neurons in the brainstem comprise the final stage of descending control of the mammalian peripheral auditory system through axon projections to the cochlea. MOC activity adjusts cochlear gain and frequency tuning, and protects the ear from acoustic trauma. The neuronal pathways that activate and modulate the MOC somata in the brainstem to drive these cochlear effects are poorly understood. Evidence suggests that MOC neurons are primarily excited by sound stimuli in a three-neuron activation loop from the auditory nerve via an intermediate neuron in the cochlear nucleus. Anatomical studies suggest that MOC neurons receive diverse synaptic inputs, but the functional effect of additional synaptic influences on MOC neuron responses is unknown. Here we use patch-clamp electrophysiological recordings from identified MOC neurons in brainstem slices from mice of either sex to demonstrate that in addition to excitatory glutamatergic synapses, MOC neurons receive inhibitory GABAergic and glycinergic synaptic inputs. These synapses are activated by electrical stimulation of axons near the medial nucleus of the trapezoid body (MNTB). Focal glutamate uncaging confirms MNTB neurons as a source of inhibitory synapses onto MOC neurons. MNTB neurons inhibit MOC action potentials, but this effect depresses with repeat activation. This work identifies a new pathway of connectivity between brainstem auditory neurons and indicates that MOC neurons are both excited and inhibited by sound stimuli received at the same ear. The pathway depression suggests that the effect of MNTB inhibition of MOC neurons diminishes over the course of a sustained sound.SIGNIFICANCE STATEMENT Medial olivocochlear (MOC) neurons are the final stage of descending control of the mammalian auditory system and exert influence on cochlear mechanics to modulate perception of acoustic stimuli. The brainstem pathways that drive MOC function are poorly understood. Here we show for the first time that MOC neurons are inhibited by neurons of the MNTB, which may suppress the effects of MOC activity on the cochlea.

Adaptation to Noise in Human Speech Recognition Depends on Noise-Level Statistics and Fast Dynamic-Range Compression.

Human hearing adapts to background noise, as evidenced by the fact that listeners recognize more isolated words when words are presented later rather than earlier in noise. This adaptation likely occurs because the leading noise shifts ("adapts") the dynamic range of auditory neurons, which can improve the neural encoding of speech spectral and temporal cues. Because neural dynamic range adaptation depends on stimulus-level statistics, here we investigated the importance of "statistical" adaptation for improving speech recognition in noisy backgrounds. We compared the recognition of noised-masked words in the presence and in the absence of adapting noise precursors whose level was either constant or was changing every 50 ms according to different statistical distributions. Adaptation was measured for 28 listeners (9 men) and was quantified as the recognition improvement in the precursor relative to the no-precursor condition. Adaptation was largest for constant-level precursors and did not occur for highly fluctuating precursors, even when the two types of precursors had the same mean level and both activated the medial olivocochlear reflex. Instantaneous amplitude compression of the highly fluctuating precursor produced as much adaptation as the constant-level precursor did without compression. Together, results suggest that noise adaptation in speech recognition is probably mediated by neural dynamic range adaptation to the most frequent sound level. Further, they suggest that auditory peripheral compression per se, rather than the medial olivocochlear reflex, could facilitate noise adaptation by reducing the level fluctuations in the noise.SIGNIFICANCE STATEMENT Recognizing speech in noise is challenging but can be facilitated by noise adaptation. The neural mechanisms underlying this adaptation remain unclear. Here, we report some benefits of adaptation for word-in-noise recognition and show that (1) adaptation occurs for stationary but not for highly fluctuating precursors with equal mean level; (2) both stationary and highly fluctuating noises activate the medial olivocochlear reflex; and (3) adaptation occurs even for highly fluctuating precursors when the stimuli are passed through a fast amplitude compressor. These findings suggest that noise adaptation reflects neural dynamic range adaptation to the most frequent noise level and that auditory peripheral compression, rather than the medial olivocochlear reflex, could facilitate noise adaptation.

Medial olivocochlear reflex effects on amplitude growth functions of long- and short-latency components of click-evoked otoacoustic emissions in humans.

Functional outcomes of medial olivocochlear reflex (MOCR) activation, such as improved hearing in background noise and protection from noise damage, involve moderate to high sound levels. Previous noninvasive measurements of MOCR in humans focused primarily on otoacoustic emissions (OAEs) evoked at low sound levels. Interpreting MOCR effects on OAEs at higher levels is complicated by the possibility of the middle-ear muscle reflex and by components of OAEs arising from different locations along the length of the cochlear spiral. We overcame these issues by presenting click stimuli at a very slow rate and by time-frequency windowing the resulting click-evoked (CE)OAEs into short-latency (SL) and long-latency (LL) components. We characterized the effects of MOCR on CEOAE components using multiple measures to more comprehensively assess these effects throughout much of the dynamic range of hearing. These measures included CEOAE amplitude attenuation, equivalent input attenuation, phase, and slope of growth functions. Results show that MOCR effects are smaller on SL components than LL components, consistent with SL components being generated slightly basal of the characteristic frequency region. Amplitude attenuation measures showed the largest effects at the lowest stimulus levels, but slope change and equivalent input attenuation measures did not decrease at higher stimulus levels. These latter measures are less commonly reported and may provide insight into the variability in listening performance and noise susceptibility seen across individuals.NEW & NOTEWORTHY The auditory efferent system, operating at moderate to high sound levels, may improve hearing in background noise and provide protection from noise damage. We used otoacoustic emissions to measure these efferent effects across a wide range of sound levels and identified level-dependent and independent effects. Previous reports have focused on level-dependent measures. The level-independent effects identified here may provide new insights into the functional relevance of auditory efferent activity in humans.

Reliability of contralateral suppression of otoacoustic emissions in children.

OBJECTIVE: The purpose of the study was to determine the reliability in children of the medial olivocochlear reflex when measured as decibels of suppression of transiently evoked otoacoustic emissions (TEOAEs) by contralateral acoustic stimulation (CAS). DESIGN: TEOAEs with and without CAS (white noise) were measured. In each subject, measurements were performed twice. Of particular interest was the suppression of TEOAEs by CAS and its reliability. Reliability was evaluated by calculating the standard error of measurement (SEM) and minimum detectable change (MDC). STUDY SAMPLE: Fifty-one normally hearing girls aged 3-6 years. RESULTS: The average global TEOAE suppression was around 0.6 dB. The highest reliability was for global values, with SEM of 0.2 dB and MDC of ±0.55 dB for the standard 2.5-20 ms recording window and slightly higher values for an 8-18 ms window. The worst reliability in the studied group was for the 1 kHz half-octave frequency band. Additionally, ears without spontaneous otoacoustic emissions had higher suppression levels than those with, but they also had lower signal-to-noise ratios, which may limit their clinical utility. CONCLUSIONS: The current study shows that, under the studied paradigm, TEOAE suppression does not have satisfactory reliability since MDC was similar to the level of suppression.

Efferent unmasking of speech-in-noise encoding?

OBJECTIVE: The medial olivocochlear (MOC) reflex provides efferent feedback from the brainstem to cochlear outer hair cells. Physiologic studies have demonstrated that the MOC reflex is involved in "unmasking" of signals-in-noise at the level of the auditory nerve; however, its functional importance in human hearing remains unclear. DESIGN: This study examined relationships between pre-neural measurements of MOC reflex strength (click-evoked otoacoustic emission inhibition; CEOAE) and neural measurements of speech-in-noise encoding (speech frequency following response; sFFR) in four conditions (Quiet, Contralateral Noise, Ipsilateral Noise, and Ipsilateral + Contralateral Noise). Three measures of CEOAE inhibition (amplitude reduction, effective attenuation, and input-output slope inhibition) were used to quantify pre-neural MOC reflex strength. Correlations between pre-neural MOC reflex strength and sFFR "unmasking" (i.e. response recovery from masking effects with activation of the MOC reflex in time and frequency domains) were assessed. STUDY SAMPLE: 18 young adults with normal hearing. RESULTS: sFFR unmasking effects were insignificant, and there were no correlations between pre-neural MOC reflex strength and sFFR unmasking in the time or frequency domain. CONCLUSION: Our results do not support the hypothesis that the MOC reflex is involved in speech-in-noise neural encoding, at least for features that are represented in the sFFR at the SNR tested.

The role of efferents in human auditory development: efferent inhibition predicts frequency discrimination in noise for children.

The descending corticofugal fibers originate from the auditory cortex and exert control on the periphery via the olivocochlear efferents. Medial efferents are thought to enhance the discriminability of transient sounds in background noise. In addition, the observation of deleterious long-term effects of efferent sectioning on the response properties of auditory nerve fibers in neonatal cats supports an efferent-mediated control of normal development. However, the role of the efferent system in human hearing remains unclear. The objective of the present study was to test the hypothesis that the medial efferents are involved in the development of frequency discrimination in noise. The hypothesis was examined with a combined behavioral and physiological approach. Frequency discrimination in noise and efferent inhibition were measured in 5- to 12-yr-old children (n = 127) and young adults (n = 37). Medial efferent strength was noninvasively assayed with a rigorous otoacoustic emission protocol. Results revealed an age-mediated relationship between efferent inhibition and frequency discrimination in noise. Efferent inhibition strongly predicted frequency discrimination in noise for younger children (5-9 yr). However, for older children (>9 yr) and adults, efferent inhibition was not related to frequency discrimination in noise. These findings support the role of efferents in the development of hearing-in-noise in humans; specifically, younger children compared with older children and adults are relatively more dependent on efferent inhibition for extracting relevant cues in noise. Additionally, the present findings caution against postulating an oversimplified relationship between efferent inhibition and measures of auditory perception in humans.NEW & NOTEWORTHY Despite several decades of research, the functional role of medial olivocochlear efferents in humans remains controversial and is thought to be insignificant. Here it is shown that medial efferent inhibition strongly predicts frequency discrimination in noise for younger children but not for older children and adults. Young children are relatively more dependent on the efferent system for listening-in-noise. This study highlights the role of the efferent system in hearing-in-noise during childhood development.

Adaptation to Noise in Human Speech Recognition Unrelated to the Medial Olivocochlear Reflex.

Sensory systems constantly adapt their responses to the current environment. In hearing, adaptation may facilitate communication in noisy settings, a benefit frequently (but controversially) attributed to the medial olivocochlear reflex (MOCR) enhancing the neural representation of speech. Here, we show that human listeners (N = 14; five male) recognize more words presented monaurally in ipsilateral, contralateral, and bilateral noise when they are given some time to adapt to the noise. This finding challenges models and theories that claim that speech intelligibility in noise is invariant over time. In addition, we show that this adaptation to the noise occurs also for words processed to maintain the slow-amplitude modulations in speech (the envelope) disregarding the faster fluctuations (the temporal fine structure). This demonstrates that noise adaptation reflects an enhancement of amplitude modulation speech cues and is unaffected by temporal fine structure cues. Last, we show that cochlear implant users (N = 7; four male) show normal monaural adaptation to ipsilateral noise. Because the electrical stimulation delivered by cochlear implants is independent from the MOCR, this demonstrates that noise adaptation does not require the MOCR. We argue that noise adaptation probably reflects adaptation of the dynamic range of auditory neurons to the noise level statistics.SIGNIFICANCE STATEMENT People find it easier to understand speech in noisy environments when they are given some time to adapt to the noise. This benefit is frequently but controversially attributed to the medial olivocochlear efferent reflex enhancing the representation of speech cues in the auditory nerve. Here, we show that the adaptation to noise reflects an enhancement of the slow fluctuations in amplitude over time that are present in speech. In addition, we show that adaptation to noise for cochlear implant users is not statistically different from that for listeners with normal hearing. Because the electrical stimulation delivered by cochlear implants is independent from the medial olivocochlear efferent reflex, this demonstrates that adaptation to noise does not require this reflex.

Enhancement of the Medial Olivocochlear System Prevents Hidden Hearing Loss.

Cochlear synaptopathy produced by exposure to noise levels that cause only transient auditory threshold elevations is a condition that affects many people and is believed to contribute to poor speech discrimination in noisy environments. These functional deficits in hearing, without changes in sensitivity, have been called hidden hearing loss (HHL). It has been proposed that activity of the medial olivocochlear (MOC) system can ameliorate acoustic trauma effects. Here we explore the role of the MOC system in HHL by comparing the performance of two different mouse models: an α9 nicotinic receptor subunit knock-out (KO; Chrna9 KO), which lacks cholinergic transmission between efferent neurons and hair cells; and a gain-of-function knock-in (KI; Chrna9L9'T KI) carrying an α9 point mutation that leads to enhanced cholinergic activity. Animals of either sex were exposed to sound pressure levels that in wild-type produced transient cochlear threshold shifts and a decrease in neural response amplitudes, together with the loss of ribbon synapses, which is indicative of cochlear synaptopathy. Moreover, a reduction in the number of efferent contacts to outer hair cells was observed. In Chrna9 KO ears, noise exposure produced permanent auditory threshold elevations together with cochlear synaptopathy. In contrast, the Chrna9L9'T KI was completely resistant to the same acoustic exposure protocol. These results show a positive correlation between the degree of HHL prevention and the level of cholinergic activity. Notably, enhancement of the MOC feedback promoted new afferent synapse formation, suggesting that it can trigger cellular and molecular mechanisms to protect and/or repair the inner ear sensory epithelium.SIGNIFICANCE STATEMENT Noise overexposure is a major cause of a variety of perceptual disabilities, including speech-in-noise difficulties, tinnitus, and hyperacusis. Here we show that exposure to noise levels that do not cause permanent threshold elevations or hair cell death can produce a loss of cochlear nerve synapses to inner hair cells as well as degeneration of medial olivocochlear (MOC) terminals contacting the outer hair cells. Enhancement of the MOC reflex can prevent both types of neuropathy, highlighting the potential use of drugs that increase α9α10 nicotinic cholinergic receptor activity as a pharmacotherapeutic strategy to avoid hidden hearing loss.

Assessment of the efferent auditory system in children with suspected auditory processing disorder: the Middle ear muscle reflex and contralateral inhibition of OAEs.

OBJECTIVE: To determine whether children aged 7 to 12 years with listening difficulties show objective evidence for efferent auditory function based on measurements of medial olivo-cochlear and middle ear muscle reflexes. DESIGN: Click-evoked otoacoustic emissions recorded with and without contralateral broadband noise and ipsilateral and contralateral tonal (1000, 2000 Hz) middle ear muscle reflex thresholds were examined. STUDY SAMPLE: 29 children diagnosed with suspected auditory processing disorder (APD) and a control group of 34 typically developing children participated in this study. RESULTS: Children with suspected APD had poorer performance on auditory processing tests than the control group. Middle ear muscle reflex thresholds were significantly higher at 2000 Hz in the suspected APD group for contralateral stimulation. MOC inhibition effects did not differ between APD and control groups. CONCLUSIONS: This research supports earlier studies showing altered acoustic reflexes in children with APD. No group differences were found for the MOC reflex measures, consistent with some earlier studies in children with APD.

Evaluation of medial olivocochlear efferent system and hearing loss in patients with primary Sjögren's syndrome

Background/aim: Autoimmune diseases are a remarkable issue for researchers due to their adverse effects on the auditory system, but for primary Sjögren's syndrome (pSS) there is little research on the comprehensive audiological findings in literature. The main objective of this study was to investigate the medial olivocochlear efferent functions of subjects with pSS and to examine the audiological findings. Materials and methods: The study included 36 subjects with pSS and 36 healthy subjects. All the subjects underwent testing including pure tone, speech, and high frequency audiometry; tympanometry and acoustic reflexes; distortion product otoacoustic emissions (DPOAE); and suppression of DPOAE. Results: The hearing thresholds of the pSS group were higher than those of the control at all frequencies (P < 0.001). Minimal to mild sensorineural hearing loss was observed in 52.77% of all the subjects with pSS. Additionally, all of the subjects had type A curve tympanograms, but the static compliances of the pSS group were lower and the acoustic reflex thresholds were higher than in the control (P < 0.001). In suppression levels of DPOAE, no statistically significant difference was found between the groups (P > 0.05). Conclusion: The study indicates that because of obtaining normal suppression levels in DPOAE, the medial olivocochlear efferent system is functional in pSS. However, there is a need for more tests, including auditory brainstem response, to evaluate the afferent auditory system in pSS.

mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea.

KEY POINTS: Spontaneous activity of the sensory inner hair cells shapes maturation of the developing ascending (afferent) auditory system before hearing begins. Just before the onset of hearing, descending (efferent) input from cholinergic neurons originating in the brainstem inhibit inner hair cell spontaneous activity and may further refine maturation. We show that agonist activation of the group I metabotropic glutamate receptor mGluR1 increases the strength of this efferent inhibition by enhancing the presynaptic release of acetylcholine. We further show that the endogenous release of glutamate from the inner hair cells may increase the strength of efferent inhibition via the activation of group I metabotropic glutamate receptors. Thus, before the onset of hearing, metabotropic glutamate signalling establishes a local negative feedback loop that is positioned to regulate inner hair cell excitability and refine maturation of the auditory system. ABSTRACT: Just before the onset of hearing, the inner hair cells (IHCs) receive inhibitory efferent input from cholinergic medial olivocochlear (MOC) neurons originating in the brainstem. This input may serve a role in the maturation of the ascending (afferent) auditory system by inhibiting spontaneous activity of the IHCs. To investigate the molecular mechanisms regulating these IHC efferent synapses, we combined electrical stimulation of the efferent fibres with patch clamp recordings from the IHCs to measure efferent synaptic strength. By examining evoked responses, we show that activation of metabotropic glutamate receptors (mGluRs) by general and group I-specific mGluR agonists enhances IHC efferent inhibition. This enhancement is blocked by application of a group I mGluR1-specific antagonist, indicating that enhancement of IHC efferent inhibition is mediated by group I mGluRs and specifically by mGluR1s. By comparing spontaneous and evoked responses, we show that group I mGluR agonists act presynaptically to increase neurotransmitter release without affecting postsynaptic responsiveness. Moreover, endogenous glutamate released from the IHCs also enhances IHC efferent inhibition via the activation of group I mGluRs. Finally, immunofluorescence analysis indicates that the efferent terminals are sufficiently close to IHC glutamate release sites to allow activation of mGluRs on the efferent terminals by glutamate spillover. Together, these results suggest that glutamate released from the IHCs activates group I mGluRs (mGluR1s), probably present on the efferent terminals, which, in turn, enhances release of acetylcholine and inhibition of the IHCs. Thus, mGluRs establish a local negative feedback loop positioned to regulate IHC activity and maturation of the ascending auditory system in the developing cochlea.

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.

Differences in the suppression of distortion product otoacoustic emissions by contralateral white noise between patients with acute or chronic tinnitus.

OBJECTIVE: The mechanisms underlying the shift from acute tinnitus to chronic remain obscure. An association between tinnitus and medial olivocochlear bundle (MOCB) reflex dysfunction has been hypothesised by several studies. The differences between participants with acute and chronic tinnitus have not yet been investigated. DESIGN: Participants were examined with distortion product otoacoustic emissions (DPOAEs) suppression elicited by contralateral white noise. They were compared in terms of frequency regions with non-recordable DPOAEs, suppression amplitudes and the presence of DPOAE enhancement. STUDY SAMPLE: Eighteen participants with acute tinnitus, 40 age-matched adults with chronic tinnitus and 17 controls were included. All participants (aged 34.7 ± 9.6years; mean ± Standard deviation) had normal hearing. Tinnitus was bilateral in 22 participants and unilateral in 36. RESULTS: Ears with chronic tinnitus presented significantly lower DPOAE suppression amplitudes than ears with acute tinnitus (p < 0.0001). Both acute and chronic tinnitus ears present a high prevalence of enhancement, significantly different from controls (p < 0.0001, p = 0.0002, respectively). Non-recordable DPOAEs were significantly more frequent in the chronic than in the acute tinnitus and control groups (p < 0.0001). CONCLUSIONS: The differences between study groups indicate that when tinnitus becomes chronic, DPOAEs suppression presents changes that might reveal corresponding steps in tinnitus pathophysiology. Treatment implications are discussed.

Aging Effects on Behavioural Estimates of Suppression with Short Suppressors.

Auditory two-tone suppression is a nearly instantaneous reduction in the response of the basilar membrane to a tone or noise when a second tone or noise is presented simultaneously. Previous behavioural studies provide conflicting evidence on whether suppression changes with increasing age, and aging effects may depend on whether a suppressor above (high-side) or below (low-side) the signal frequency is used. Most previous studies have measured suppression using stimuli long enough to elicit the medial olivocochlear reflex (MOCR), a sound-elicited reflex that reduces cochlear amplification or gain. It has a "sluggish" onset of approximately 25 ms. There is physiological evidence that suppression may be reduced or altered by elicitation of the MOCR. In the present study, suppression was measured behaviourally in younger adults and older adults using a forward-masking paradigm with 20-ms and 70-ms maskers and suppressors. In experiment 1, gain was estimated by comparing on-frequency (2 kHz) and off-frequency (1.2 kHz) masker thresholds for a short, fixed-level 2-kHz signal. In experiment 2, the fixed-level signal was preceded by an off-frequency suppressor (1.2 or 2.4 kHz) presented simultaneously with the on-frequency masker. A suppressor level was chosen that did not produce any forward masking of the signal. Suppression was measured as the difference in on-frequency masker threshold with and without the suppressor present. The effects of age on gain and suppression estimates will be discussed.

Hyperactivity in the medial olivocochlear efferent system is a common feature of tinnitus and hyperacusis in humans.

Tinnitus and hyperacusis are common, burdensome sources of morbidity with a high rate of co-occurrence. Knudson et al. (J Neurophysiol 112: 3197-3208, 2014) demonstrated that efferent suppression of cochlear activity by the medial olivocochlear system is enhanced in individuals with tinnitus and/or hyperacusis. Their findings stress that atypical activity in the efferent auditory pathway may represent a shared substrate, as well as a potential therapeutic target, in tinnitus and hyperacusis.