Fast Inhibition Slows and Desynchronizes Mouse Auditory Efferent Neuron Activity.

The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem are well suited for accurate analysis of fast acoustic signals, given their physiological specializations of fast membrane time constants, fast axonal conduction, and reliable synaptic transmission. The medial olivocochlear (MOC) neurons that provide efferent inhibition of the cochlea reside in the ventral brainstem and participate in these fast neural circuits. However, their modulation of cochlear function occurs over time scales of a slower nature. This suggests the presence of mechanisms that reduce MOC inhibition of cochlear function. To determine how monaural excitatory and inhibitory synaptic inputs integrate to affect the timing of MOC neuron activity, we developed a novel in vitro slice preparation ("wedge-slice"). The wedge-slice maintains the ascending auditory nerve root, the entire CN and projecting axons, while preserving the ability to perform visually guided patch-clamp electrophysiology recordings from genetically identified MOC neurons. The "in vivo-like" timing of the wedge-slice demonstrates that the inhibitory pathway accelerates relative to the excitatory pathway when the ascending circuit is intact, and the CN portion of the inhibitory circuit is precise enough to compensate for reduced precision in later synapses. When combined with machine learning PSC analysis and computational modeling, we demonstrate a larger suppression of MOC neuron activity when the inhibition occurs with in vivo-like timing. This delay of MOC activity may ensure that the MOC system is only engaged by sustained background sounds, preventing a maladaptive hypersuppression of cochlear activity.

Direct Cochlear Recordings in Humans Show a Theta Rhythmic Modulation of Auditory Nerve Activity by Selective Attention.

The architecture of the efferent auditory system enables prioritization of strongly overlapping spatiotemporal cochlear activation patterns elicited by relevant and irrelevant inputs. So far, attempts at finding such attentional modulations of cochlear activity delivered indirect insights in humans or required direct recordings in animals. The extent to which spiral ganglion cells forming the human auditory nerve are sensitive to selective attention remains largely unknown. We investigated this question by testing the effects of attending to either the auditory or visual modality in human cochlear implant (CI) users (3 female, 13 male). Auditory nerve activity was directly recorded with standard CIs during a silent (anticipatory) cue-target interval. When attending the upcoming auditory input, ongoing auditory nerve activity within the theta range (5-8 Hz) was enhanced. Crucially, using the broadband signal (4-25 Hz), a classifier was even able to decode the attended modality from single-trial data. Follow-up analysis showed that the effect was not driven by a narrow frequency in particular. Using direct cochlear recordings from deaf individuals, our findings suggest that cochlear spiral ganglion cells are sensitive to top-down attentional modulations. Given the putatively broad hair-cell degeneration of these individuals, the effects are likely mediated by alternative efferent pathways compared with previous studies using otoacoustic emissions. Successful classification of single-trial data could additionally have a significant impact on future closed-loop CI developments that incorporate real-time optimization of CI parameters based on the current mental state of the user.SIGNIFICANCE STATEMENT The efferent auditory system in principle allows top-down modulation of auditory nerve activity; however, evidence for this is lacking in humans. Using cochlear recordings in participants performing an audiovisual attention task, we show that ongoing auditory nerve activity in the silent cue-target period is directly modulated by selective attention. Specifically, ongoing auditory nerve activity is enhanced within the theta range when attending upcoming auditory input. Furthermore, over a broader frequency range, the attended modality can be decoded from single-trial data. Demonstrating this direct top-down influence on auditory nerve activity substantially extends previous works that focus on outer hair cell activity. Generally, our work could promote the use of standard cochlear implant electrodes to study cognitive neuroscientific questions.

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.

Synaptic plasticity of inhibitory synapses onto medial olivocochlear efferent neurons.

The descending auditory system modulates the ascending system at every level. The final descending, or efferent, stage comprises lateral olivocochlear and medial olivocochlear (MOC) neurons. MOC somata in the ventral brainstem project axons to the cochlea to synapse onto outer hair cells (OHC), inhibiting OHC-mediated cochlear amplification. MOC suppression of OHC function is implicated in cochlear gain control with changing sound intensity, detection of salient stimuli, attention and protection against acoustic trauma. Thus, sound excites MOC neurons to provide negative feedback of the cochlea. Sound also inhibits MOC neurons via medial nucleus of the trapezoid body (MNTB) neurons. However, MNTB-MOC synapses exhibit short-term depression, suggesting reduced MNTB-MOC inhibition during sustained stimuli. Further, due to high rates of both baseline and sound-evoked activity in MNTB neurons in vivo, MNTB-MOC synapses may be tonically depressed. To probe this, we characterized short-term plasticity of MNTB-MOC synapses in mouse brain slices. We mimicked in vivo-like temperature and extracellular calcium conditions, and in vivo-like activity patterns of fast synaptic activation rates, sustained activation and prior tonic activity. Synaptic depression was sensitive to extracellular calcium concentration and temperature. During rapid MNTB axon stimulation, postsynaptic currents in MOC neurons summated but with concurrent depression, resulting in smaller, sustained currents, suggesting tonic inhibition of MOC neurons during rapid circuit activity. Low levels of baseline MNTB activity did not significantly reduce responses to subsequent rapid activity that mimics sound stimulation, indicating that, in vivo, MNTB inhibition of MOC neurons persists despite tonic synaptic depression. KEY POINTS: Inhibitory synapses from the medial nucleus of the trapezoid body (MNTB) onto medial olivocochlear (MOC) neurons exhibit short-term plasticity that is sensitive to calcium and temperature, with enhanced synaptic depression occurring at higher calcium concentrations and at room temperature. High rates of background synaptic activity that mimic the upper limits of spontaneous MNTB activity cause tonic synaptic depression of MNTB-MOC synapses that limits further synaptic inhibition. High rates of activity at MNTB-MOC synapses cause synaptic summation with concurrent depression to yield a response with an initial large amplitude that decays to a tonic inhibition.

Olivocochlear projections contribute to superior intensity coding in cochlear nucleus small cells.

Understanding communication signals, especially in noisy environments, is crucial to social interactions. Yet, as we age, acoustic signals can be disrupted by cochlear damage and the subsequent auditory nerve fibre degeneration. The most vulnerable medium- and high-threshold-auditory nerve fibres innervate various cell types in the cochlear nucleus, among which the small cells are unique in receiving this input exclusively. Furthermore, small cells project to medial olivocochlear (MOC) neurons, which in turn send branched collaterals back into the small cell cap. Here, we use single-unit recordings to characterise small cell firing characteristics and demonstrate superior intensity coding in this cell class. We show converse effects when activating/blocking the MOC system, demonstrating that small-cell unique coding properties are facilitated by direct cholinergic input from the MOC system. Small cells also maintain tone-level coding in the presence of background noise. Finally, small cells precisely code low-frequency modulation more accurately than other ventral cochlear nucleus cell types, demonstrating accurate envelope coding that may be important for vocalisation processing. These results highlight the small cell olivocochlear circuit as a key player in signal processing in noisy environments, which may be selectively degraded in ageing or after noise insult. KEY POINTS: Cochlear nucleus small cells receive input from low/medium spontaneous rate auditory nerve fibres and medial olivocochlear neurons. Electrical stimulation of medial olivocochlear neurons in the ventral nucleus of the trapezoid body and blocking cholinergic input to small cells using atropine demonstrates an excitatory cholinergic input to small cells, which increases responses to suprathreshold sound. Unique inputs to small cells produce superior sound intensity coding. This coding of intensity is preserved in the presence of background noise, an effect exclusive to this cell type in the cochlear nucleus. These results suggest that small cells serve an essential function in the ascending auditory system, which may be relevant to disorders such as hidden hearing loss.

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.

Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea.

KEY POINTS: Age-related hearing loss is a progressive hearing loss involving environmental and genetic factors, leading to a decrease in hearing sensitivity, threshold and speech discrimination. We compared age-related changes in inner hair cells (IHCs) between four mouse strains with different levels of progressive hearing loss. The surface area of apical coil IHCs (9-12 kHz cochlear region) decreases by about 30-40% with age. The number of BK channels progressively decreases with age in the IHCs from most mouse strains, but the basolateral membrane current profile remains unchanged. The mechanoelectrical transducer current is smaller in mice harbouring the hypomorphic Cdh23 allele Cdh23ahl (C57BL/6J; C57BL/6NTac), but not in Cdh23-repaired mice (C57BL/6NTacCdh23+ ), indicating that it could contribute to the different progression of hearing loss among mouse strains. The degree of efferent rewiring onto aged IHCs, most likely coming from the lateral olivocochlea fibres, was correlated with hearing loss in the different mouse strains. ABSTRACT: Inner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea, transducing acoustic information into electrical signals that are relayed to the afferent neurons. Functional changes in IHCs are a potential cause of age-related hearing loss. Here, we have investigated the functional characteristics of IHCs from early-onset hearing loss mice harbouring the allele Cdh23ahl (C57BL/6J and C57BL/6NTac), from late-onset hearing loss mice (C3H/HeJ), and from mice corrected for the Cdh23ahl mutation (C57BL/6NTacCdh23+ ) with an intermediate hearing phenotype. There was no significant loss of IHCs in the 9-12 kHz cochlear region up to at least 15 months of age, but their surface area decreased progressively by 30-40% starting from ∼6 months of age. Although the size of the BK current decreased with age, IHCs retained a normal KCNQ4 current and resting membrane potential. These basolateral membrane changes were most severe for C57BL/6J and C57BL/6NTac, less so for C57BL/6NTacCdh23+ and minimal or absent in C3H/HeJ mice. We also found that lateral olivocochlear (LOC) efferent fibres re-form functional axon-somatic connections with aged IHCs, but this was seen only sporadically in C3H/HeJ mice. The efferent post-synaptic SK2 channels appear prior to the establishment of the efferent contacts, suggesting that IHCs may play a direct role in re-establishing the LOC-IHC synapses. Finally, we showed that the size of the mechanoelectrical transducer (MET) current from IHCs decreased significantly with age in mice harbouring the Cdh23ahl allele but not in C57BL/6NTacCdh23+ mice, indicating that the MET apparatus directly contributes to the progression of age-related hearing loss.

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.

The medial olivocochlear reflex strength is modulated during a visual working memory task.

Top-down modulation of sensory responses to distracting stimuli by selective attention has been proposed as an important mechanism by which our brain can maintain relevant information during working memory tasks. Previous works in visual working memory (VWM) have reported modulation of neural responses to distracting sounds at different levels of the central auditory pathways. Whether these modulations occur also at the level of the auditory receptor is unknown. Here, we hypothesize that cochlear responses to irrelevant auditory stimuli can be modulated by the medial olivocochlear system during VWM. Twenty-one subjects (13 males, mean age 25.3 yr) with normal hearing performed a visual change detection task with different VWM load conditions (high load = 4 visual objects; low load = 2 visual objects). Auditory stimuli were presented as distractors and allowed the measurement of distortion product otoacoustic emissions (DPOAEs) and scalp auditory evoked potentials. In addition, the medial olivocochlear reflex strength was evaluated by adding contralateral acoustic stimulation. We found larger contralateral acoustic suppression of DPOAEs during the visual working memory period (n = 21) compared with control experiments (n = 10), in which individuals were passively exposed to the same experimental conditions. These results show that during the visual working memory period there is a modulation of the medial olivocochlear reflex strength, suggesting a possible common mechanism for top-down filtering of auditory responses during cognitive processes.NEW & NOTEWORTHY The auditory efferent system has been proposed to function as a biological filter of cochlear responses during selective attention. Here, we recorded electroencephalographic activity and otoacoustic emissions in response to auditory distractors during a visual working memory task in humans. We found that the olivocochlear efferent activity is modulated during the visual working memory period suggesting a common mechanism for suppressing cochlear responses during selective attention and working memory.

The role of the medial olivocochlear reflex in psychophysical masking and intensity resolution in humans: a review.

This review addresses the putative role of the medial olivocochlear (MOC) reflex in psychophysical masking and intensity resolution in humans. A framework for interpreting psychophysical results in terms of the expected influence of the MOC reflex is introduced. This framework is used to review the effects of a precursor or contralateral acoustic stimulation on 1) simultaneous masking of brief tones, 2) behavioral estimates of cochlear gain and frequency resolution in forward masking, 3) the buildup and decay of forward masking, and 4) measures of intensity resolution. Support, or lack thereof, for a role of the MOC reflex in psychophysical perception is discussed in terms of studies on estimates of MOC strength from otoacoustic emissions and the effects of resection of the olivocochlear bundle in patients with vestibular neurectomy. Novel, innovative approaches are needed to resolve the dissatisfying conclusion that current results are unable to definitively confirm or refute the role of the MOC reflex in masking and intensity resolution.

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.

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.

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.

Establishing critical differences in ear-canal stimulus amplitude for detecting middle ear muscle reflex activation during olivocochlear efferent measurements.

Objective: Assessments of the medial olivocochlear reflex (MOCR) may have clinical utility. The MOCR is measured using contralateral inhibition of otoacoustic emissions but concurrent activation of the middle ear muscle reflex (MEMR) confounds test interpretation. MEMR activation can be detected using the change in ear-canal stimulus amplitude without versus with an MOCR elicitor. This study provides a description of how critical differences in ear-canal stimulus amplitude can be established.Design: Clicks were presented in right ears without and with a contralateral MOCR elicitor. Ear-canal stimulus amplitudes were measured. Two measurements without an elicitor were used to develop critical differences. MEMR activation was considered present if the difference in ear-canal stimulus amplitude without versus with an elicitor exceeded the critical difference.Study sample: Forty-six normal-hearing adults (mean age = 23.4 years, 35 females) participated, with data from 44 participants included in the final analysis.Results: Two participants exceeded the 95% critical difference. The 80, 90 and 99% critical differences are also reported for reference.Conclusions: Results suggest that the contralateral elicitor can evoke the MEMR in a small number of participants. The methods described in this paper can be used for developing equipment- and clinic-specific critical differences for detecting MEMR activation.

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.