Medial Olivocochlear Inhibition Research Articles

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 hyper-suppression of cochlear activity.Significance Statement Auditory brainstem neurons are specialized for speed and fidelity to encode rapid features of sound. Extremely fast inhibition contributes to precise brainstem sound encoding. This circuit also projects to medial olivocochlear (MOC) efferent neurons that suppress cochlear function to enhance detection of signals in background sound. Using a novel brain slice preparation with intact ascending circuitry, we show that inhibition of MOC neurons can also be extremely fast, with the speed of the circuit localized to the cochlear nucleus. In contrast with the enhancement of precision afforded by fast inhibition in other brainstem auditory circuits, inhibition to MOC neurons instead has a variable onset that delays and desynchronizes activity, thus reducing precision for a slow, sustained response to background sounds.

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.

Medial olivocochlear suppression in musicians versus non-musicians.

The medial olivocochlear efferent (MOCE) branch synapses with outer hair cells (OHCs), and the efferent pathway can be activated via a contralateral acoustic stimulus (CAS). The activation of MOCE can change OHC motile responses and convert signals that are capable of controlling the sensitivity of the peripheral hearing system in a frequency-specific manner. The aim of this study was to examine the MOCE system activity in professional musicians using transient evoked otoacoustic emission test and CAS. Musician group showed stronger suppression in all frequency bands in the presence of CAS.

Objective speech transmission improvements with a binaural cochlear implant sound-coding strategy inspired by the contralateral medial olivocochlear reflex.

It has been recently shown that cochlear implant users could enjoy better speech reception in noise and enhanced spatial unmasking with binaural audio processing inspired by the inhibitory effects of the contralateral medial olivocochlear (MOC) reflex on compression [Lopez-Poveda, Eustaquio-Martin, Stohl, Wolford, Schatzer, and Wilson (2016). Ear Hear. 37, e138-e148]. The perceptual evidence supporting those benefits, however, is limited to a few target-interferer spatial configurations and to a particular implementation of contralateral MOC inhibition. Here, the short-term objective intelligibility index is used to (1) objectively demonstrate potential benefits over many more spatial configurations, and (2) investigate if the predicted benefits may be enhanced by using more realistic MOC implementations. Results corroborate the advantages and drawbacks of MOC processing indicated by the previously published perceptual tests. The results also suggest that the benefits may be enhanced and the drawbacks overcome by using longer time constants for the activation and deactivation of inhibition and, to a lesser extent, by using a comparatively greater inhibition in the lower than in the higher frequency channels. Compared to using two functionally independent processors, the better MOC processor improved the signal-to-noise ratio in the two ears between 1 and 6 decibels by enhancing head-shadow effects, and was advantageous for all tested target-interferer spatial configurations.

A Gain-of-Function Mutation in the α9 Nicotinic Acetylcholine Receptor Alters Medial Olivocochlear Efferent Short-Term Synaptic Plasticity.

Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher-processing centers. Efferent activation inhibits OHC active amplification within the mammalian cochlea, through the activation of a calcium-permeable α9α10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels. Correct operation of this feedback requires careful matching of acoustic input with the strength of cochlear inhibition (Galambos, 1956; Wiederhold and Kiang, 1970; Gifford and Guinan, 1987), which is driven by the rate of MOC activity and short-term facilitation at the MOC-OHC synapse (Ballestero et al., 2011; Katz and Elgoyhen, 2014). The present work shows (in mice of either sex) that a mutation in the α9α10 nAChR with increased duration of channel gating (Taranda et al., 2009) greatly elongates hair cell-evoked IPSCs and Ca2+ signals. Interestingly, MOC-OHC synapses of L9'T mice presented reduced quantum content and increased presynaptic facilitation. These phenotypic changes lead to enhanced and sustained synaptic responses and OHC hyperpolarization upon high-frequency stimulation of MOC terminals. At the cochlear physiology level these changes were matched by a longer time course of efferent MOC suppression. This indicates that the properties of the MOC-OHC synapse directly determine the efficacy of the MOC feedback to the cochlea being a main player in the "gain control" of the auditory periphery.SIGNIFICANCE STATEMENT Plasticity can involve reciprocal signaling across chemical synapses. An opportunity to study this phenomenon occurs in the mammalian cochlea whose sensitivity is regulated by efferent olivocochlear neurons. These release acetylcholine to inhibit sensory hair cells. A point mutation in the hair cell's acetylcholine receptor that leads to increased gating of the receptor greatly elongates IPSCs. Interestingly, efferent terminals from mutant mice present a reduced resting release probability. However, upon high-frequency stimulation transmitter release facilitates strongly to produce stronger and far longer-lasting inhibition of cochlear function. Thus, central neuronal feedback on cochlear hair cells provides an opportunity to define plasticity mechanisms in cholinergic synapses other than the highly studied neuromuscular junction.

The effects of noise exposure and musical training on suprathreshold auditory processing and speech perception in noise

Recent animal research has shown that exposure to single episodes of intense noise causes cochlear synaptopathy without affecting hearing thresholds. It has been suggested that the same may occur in humans. If so, it is hypothesized that this would result in impaired encoding of sound and lead to difficulties hearing at suprathreshold levels, particularly in challenging listening environments. The primary aim of this study was to investigate the effect of noise exposure on auditory processing, including the perception of speech in noise, in adult humans. A secondary aim was to explore whether musical training might improve some aspects of auditory processing and thus counteract or ameliorate any negative impacts of noise exposure. In a sample of 122 participants (63 female) aged 30–57 years with normal or near-normal hearing thresholds, we conducted audiometric tests, including tympanometry, audiometry, acoustic reflexes, otoacoustic emissions and medial olivocochlear responses. We also assessed temporal and spectral processing, by determining thresholds for detection of amplitude modulation and temporal fine structure. We assessed speech-in-noise perception, and conducted tests of attention, memory and sentence closure. We also calculated participants' accumulated lifetime noise exposure and administered questionnaires to assess self-reported listening difficulty and musical training. The results showed no clear link between participants' lifetime noise exposure and performance on any of the auditory processing or speech-in-noise tasks. Musical training was associated with better performance on the auditory processing tasks, but not the on the speech-in-noise perception tasks. The results indicate that sentence closure skills, working memory, attention, extended high frequency hearing thresholds and medial olivocochlear suppression strength are important factors that are related to the ability to process speech in noise.

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.

Electrically Evoked Medial Olivocochlear Efferent Effects on Stimulus Frequency Otoacoustic Emissions in Guinea Pigs.

Stimulus frequency otoacoustic emissions (SFOAEs) are produced by cochlear irregularities reflecting energy from the peak region of the traveling wave (TW). Activation of medial olivocochlear (MOC) efferents reduces cochlear amplification and otoacoustic emissions (OAEs). In other OAEs, MOC activation can produce enhancements. The extent of MOC enhancements of SFOAEs has not been previously studied. In anesthetized guinea pigs, we electrically stimulated MOC fibers and recorded their effects on SFOAEs. MOC stimulation mostly inhibited SFOAEs but sometimes enhanced them. Some enhancements were not near response dips and therefore cannot be explained by a reduction of wavelet cancelations. MOC stimulation always inhibited auditory-nerve compound action potentials showing that cochlear-amplifier gain was not increased. We propose that some SFOAE enhancements arise because shocks excite only a small number of MOC fibers that inhibit a few scattered outer hair cells thereby changing (perhaps increasing) cochlear irregularities and SFOAE amplitudes. Contralateral sound activation is expected to excite approximately one third of MOC efferents and may also change cochlear irregularities. Some papers suggest that large SFOAE components originate far basal of the TW peak, basal of the region that receives cochlear amplification. Using a time-frequency analysis, we separated SFOAEs into components with different latencies. At all SFOAE latencies, most SFOAE components were inhibited by MOC stimulation, but some were enhanced. The MOC inhibition of short-latency SFOAE components is consistent with these components being produced in the cochlear-amplified region near the TW peak.

Right-ear advantage drives the link between olivocochlear efferent 'antimasking' and speech-in-noise listening benefits.

The mammalian cochlea receives feedback from the brainstem medial olivocochlear (MOC) efferents, whose putative 'antimasking' function is to adjust cochlear amplification and enhance peripheral signal detection in adverse listening environments. Human studies have been inconsistent in demonstrating a clear connection between this corticofugal system and behavioral speech-in-noise (SIN) listening skills. To elucidate the role of brainstem efferent activity in SIN perception, we measured ear-specific contralateral suppression of transient-evoked otoacoustic emissions (OAEs), a proxy measure of MOC activation linked to auditory learning in noisy environments. We show that suppression of cochlear emissions is stronger with a more basal cochlear bias in the right ear compared with the left ear. Moreover, a strong negative correlation was observed between behavioral SIN performance and right-ear OAE suppression magnitudes, such that lower speech reception thresholds in noise were predicted by larger amounts of MOC-related activity. This brain-behavioral relation was not observed for left ear SIN perception. The rightward bias in contralateral MOC suppression of OAEs, coupled with the stronger association between physiological and perceptual measures, is consistent with left-hemisphere cerebral dominance for speech-language processing. We posit that corticofugal feedback from the left cerebral cortex through descending MOC projections sensitizes the right cochlea to signal-in-noise detection, facilitating figure-ground contrast and improving degraded speech analysis. Our findings demonstrate that SIN listening is at least partly driven by subcortical brain mechanisms; primitive stages of cochlear processing and brainstem MOC modulation of (right) inner ear mechanics play a critical role in dictating SIN understanding.

Medial efferent mechanisms in children with auditory processing disorders.

Auditory processing disorder (APD) affects about 2–5% of children. However, the nature of this disorder is poorly understood. Children with APD typically have difficulties in complex listening situations. One mechanism thought to aid in listening-in-noise is the medial olivocochlear (MOC) inhibition. The purpose of this review was to critically analyze the published data on MOC inhibition in children with APD to determine whether the MOC efferents are involved in these individuals. The otoacoustic emission (OAE) methods used to assay MOC reflex were examined in the context of the current understanding of OAE generation mechanisms. Relevant literature suggests critical differences in the study population and OAE methods. Variables currently known to influence MOC reflex measurements, for example, middle-ear muscle reflexes or OAE signal-to-noise ratio, were not controlled in most studies. The use of potentially weaker OAE methods and the remarkable heterogeneity across studies does not allow for a definite conclusion whether or not the MOC reflex is altered in children with APD. Further carefully designed studies are needed to confirm the involvement of MOC efferents in APD. Knowledge of efferent functioning in children with APD would be mechanistically and clinically beneficial.

Influence of aging on medial olivocochlear system function

BackgroundThere is still controversy regarding the influence of aging on medial olivocochlear (MOC) system function. The main objective of this study is to measure age-related changes of MOC system function in people with normal hearing thresholds.MethodBilateral assessment of the MOC effect for click-evoked otoacoustic emissions (CEOAEs; at 70±3 dB peak sound pressure level [pSPL], click at 50/second, 260 repeats, 2.5–20 millisecond window) and for distortion product otoacoustic emissions (DPOAEs; with [frequencies] f2/f1=1.22, [levels of primary tones] L1=65 dB SPL and L2=55 dB SPL; DP-grams for 2f1–f2 were collected for the f1 frequencies varying from 977 Hz to 5,164 kHz, with the resolution of four points per octave) was performed in a group of 146 (n=292 ears) healthy, right-handed subjects aged from 10–60 years with a bilateral hearing threshold from 0.25–4.0 kHz, not exceeding 20 dB hearing level; normal tympanograms; and a threshold of the contralateral stapedial reflex for broadband noise (BBN) of 75 dB SPL or higher. The MOC inhibition was assessed on the basis of changes in OAE level during BBN contralateral stimulation at 50 dB sensation level (mean, 65±3 dB SPL).ResultsComparative analysis of the MOC effect for CEOAE and DPOAE showed the weakest effect in the oldest age group (41–60 years) at almost all tested frequencies. Moreover, a weak, albeit significant, positive correlation between the level of OAE and the size of the MOC effect was documented.ConclusionOn the basis of our study, we have found a decrease in the strength of the MOC system with increasing age in normally hearing subjects, as reflected by a decrease of the OAE suppression effects in older individuals and an increase of the number of CEOAE and DPOAE enhancements during contralateral acoustic stimulation in the elderly, especially in the high-frequency range.

Medial olivocochlear efferent effects on auditory responses

Medial Olivocochlear (MOC) inhibition in one ear can be elicited by sound in either ear. Curiously, the ratio of ipsilateral/contralateral inhibition depends on sound bandwidth; the ratio is ~2 for narrow-band sounds but ~1 for wide-band sounds. Reflex amplitude also depends on elicitor bandwidth and increases as bandwidth is increased, even when elicitor-sound energy is held constant. After elicitor onset (or offset), nothing changes for 20–30 ms and then MOC inhibition builds up (or decays) over 100–300 ms. MOC inhibition has typically been measured in humans by its effects on otoacoustic emissions (OAEs). Problems in such OAE studies include inadequate signal-to-noise ratios (SNRs) and inadequate separation of MOC effects from middle-ear-muscle effects. MOC inhibition reduces basilar-membrane responses more at low levels than high levels, which increases the response SNRs of higher-level signals relative to lower-level background noises, and reduces noise-induced adaptation. The net effect is expected to be increased intelligibility of sounds such as speech. Numerous studies have looked for such perceptual benefits of MOC activity with mixed results. More work is needed to determine whether the differing results are due to experimental conditions (e.g., the speech and noise levels used) or to methodological weaknesses. [Work supported by NIH-RO1DC005977.]

Top-down influences of the medial olivocochlear efferent system in speech perception in noise.

One of the putative functions of the medial olivocochlear (MOC) system is to enhance signal detection in noise. The objective of this study was to elucidate the role of the MOC system in speech perception in noise. In normal-hearing human listeners, we examined (1) the association between magnitude of MOC inhibition and speech-in-noise performance, and (2) the association between MOC inhibition and the amount of contralateral acoustic stimulation (CAS)-induced shift in speech-in-noise acuity. MOC reflex measurements in this study considered critical measurement issues overlooked in past work by: recording relatively low-level, linear click-evoked otoacoustic emissions (CEOAEs), adopting 6 dB signal-to-noise ratio (SNR) criteria, and computing normalized CEOAE differences. We found normalized index to be a stable measure of MOC inhibition (mean = 17.21%). MOC inhibition was not related to speech-in-noise performance measured without CAS. However, CAS in a speech-in-noise task caused an SNRSP enhancement (mean = 2.45 dB), and this improvement in speech-in-noise acuity was directly related to their MOC reflex assayed by CEOAEs. Individuals do not necessarily use the available MOC-unmasking characteristic while listening to speech in noise, or do not utilize unmasking to the extent that can be shown by artificial MOC activation. It may be the case that the MOC is not actually used under natural listening conditions and the higher auditory centers recruit MOC-mediated mechanisms only in specific listening conditions–those conditions remain to be investigated.

Acoustic Stapedius Reflex Function in Man Revisited

The objective of this study was to examine the role of the acoustic stapedius reflex in the protection of speech recognition from the upward spread of masking arising from low-frequency background noise. Speech recognition scores were measured for nine control participants (19-34 years) and six patients with transected stapedius tendons poststapedotomy (39-57 years) as a function of the amplitude of a low-frequency masker, presented at nominal signal to noise ratios of +5 dB, -5 dB, and -15 dB. All participants had pure-tone hearing thresholds in the normal range. Continuous high-pass noise was present in all conditions to avoid ceiling effects; this reduced performance in quiet to approximately 85% for all participants. Scores were measured for soft and loud nonsense syllables (average third octave band levels of 35 and 65 dB SPL), so that a comparison of the low-frequency noise masking functions at the two levels would provide information about the effects of the reflex on speech intelligibility in noise. A third group of nine control participants (19-22 years) listened in the presence of a low-frequency masker gated to come on 1 sec before stimulus onset, to reduce the likelihood of reflex adaptation. The Speech-Intelligibility Index was used to quantify the amount of speech information available in each condition. Patients with transected tendons performed more poorly than control participants as a function of Speech-Intelligibility Index in all conditions, even at levels that were too soft for reflex activation. This could be because of postsurgical differences in sensitivity, the more advanced age of poststapedotomy group, or differences in medial olivocochlear inhibition. For loud speech, patient performance fell nearly linearly with increases in the low-frequency masker, but control participants' performance declined little as the signal to noise ratio declined from +5 to -5 dB, and then fell rapidly as the ratio declined to -15 dB. This plateau in the masking function did not occur for the patients. Masking functions obtained with the gated low-frequency masker were either highly similar or poorer to those obtained with a continuous masker, suggesting that the use of a continuous low frequency masker did not result in significant reflex adaptation. The stapedius reflex appears to offer some protection from the upward spread of masking of speech by background low-frequency noise at moderate levels, but not at high levels.

How are inner hair cells stimulated? Evidence for multiple mechanical drives

Recent studies indicate that the gap over outer hair cells (OHCs) between the reticular lamina (RL) and the tectorial membrane (TM) varies cyclically during low-frequency sounds. Variation in the RL-TM gap produces radial fluid flow in the gap that can drive inner hair cell (IHC) stereocilia. Analysis of RL-TM gap changes reveals three IHC drives in addition to classic SHEAR. For upward basilar-membrane (BM) motion, IHC stereocilia are deflected in the excitatory direction by SHEAR and OHC-MOTILITY, but in the inhibitory direction by TM-PUSH and CILIA-SLANT. Upward BM motion causes OHC somatic contraction which tilts the RL, compresses the RL-TM gap over IHCs and expands the RL-TM gap over OHCs, thereby producing an outward (away from the IHCs) radial fluid flow which is the OHC-MOTILITY drive. For upward BM motion, the force that moves the TM upward also compresses the RL-TM gap over OHCs causing inward radial flow past IHCs which is the TM-PUSH drive. Motions that produce large tilting of OHC stereocilia squeeze the supra-OHC RL-TM gap and caused inward radial flow past IHCs which is the CILIA-SLANT drive. Combinations of these drives explain: (1) the reversal at high sound levels of auditory nerve (AN) initial peak (ANIP) responses to clicks, and medial olivocochlear (MOC) inhibition of ANIP responses below, but not above, the ANIP reversal, (2) dips and phase reversals in AN responses to tones in cats and chinchillas, (3) hypersensitivity and phase reversals in tuning-curve tails after OHC ablation, and (4) MOC inhibition of tail-frequency AN responses. The OHC-MOTILITY drive provides another mechanism, in addition to BM motion amplification, that uses active processes to enhance the output of the cochlea. The ability of these IHC drives to explain previously anomalous data provides strong, although indirect, evidence that these drives are significant and presents a new view of how the cochlea works at frequencies below 3 kHz.

Influence of acute hyperglycemia on otoacoustic emissions and the medial olivocochlear reflex

Stimulus-frequency (SF) otoacoustic emission (OAE) amplitude and the amplitude of medial olivocochlear (MOC) inhibition of SF OAEs for ipsilateral, contralateral and bilateral MOC reflex elicitors were recorded in six subjects with type 2 diabetes during a glucose tolerance test (GTT). Five of the six subjects were tested twice for a total of 11 trials and three subjects were tested in a control experiment. During the GTT experiment, the subjects' blood glucose was elevated from a euglycemic level below 150 mg/dL to a hyperglycemic level above 160 mg/dL following the consumption of a bolus of 80 g of sugar. A subset of three subjects were tested in a control experiment during which SF OAE and MOC reflex measurements were made while blood sugar levels remained constant within the euglycemic region. Mean SF OAE amplitudes were elevated following glucose consumption. A statistically significant increase in MOC inhibition amplitude was observed during elevated sugar levels for the 11 GTT trials. Maximum inhibition occurred about an hour after glucose consumption when blood glucose levels peaked. Results indicate that acute hyperglycemia influences efferent control of the cochlea in people with type 2 diabetes.

Short-Term Synaptic Plasticity Regulates the Level of Olivocochlear Inhibition to Auditory Hair Cells

In the mammalian inner ear, the gain control of auditory inputs is exerted by medial olivocochlear (MOC) neurons that innervate cochlear outer hair cells (OHCs). OHCs mechanically amplify the incoming sound waves by virtue of their electromotile properties while the MOC system reduces the gain of auditory inputs by inhibiting OHC function. How this process is orchestrated at the synaptic level remains unknown. In the present study, MOC firing was evoked by electrical stimulation in an isolated mouse cochlear preparation, while OHCs postsynaptic responses were monitored by whole-cell recordings. These recordings confirmed that electrically evoked IPSCs (eIPSCs) are mediated solely by α9α10 nAChRs functionally coupled to calcium-activated SK2 channels. Synaptic release occurred with low probability when MOC-OHC synapses were stimulated at 1 Hz. However, as the stimulation frequency was raised, the reliability of release increased due to presynaptic facilitation. In addition, the relatively slow decay of eIPSCs gave rise to temporal summation at stimulation frequencies >10 Hz. The combined effect of facilitation and summation resulted in a frequency-dependent increase in the average amplitude of inhibitory currents in OHCs. Thus, we have demonstrated that short-term plasticity is responsible for shaping MOC inhibition and, therefore, encodes the transfer function from efferent firing frequency to the gain of the cochlear amplifier.

Alteration in auditory function during the ovarian cycle

This study investigates whether physiological variations in ovarian hormones during the ovarian cycle (OC) are associated with changes in auditory function. Sixteen women with normal hearing underwent auditory tests and simultaneous measurements of the hormone levels four times during OC. The auditory tests included recording of otoacoustic emissions (OAEs), the medial olivocochlear (MOC) suppression and auditory brainstem responses (ABRs). The OC was defined by oestradiol and progesterone serum levels and menstrual cycle dating. A significant spontaneous OAE frequency shift [ F(3,114.6) = 15.8, p < 0.001], with the greatest shift in the late follicular phase (highest oestrogen levels), was observed. Transient evoked OAE levels showed a consistent tendency in an increase in all frequency bands in the late follicular/early luteal stage and a decrease in the late follicular stage; TEOAE inter-session comparison indicated very small statistical differences. The MOC suppression changed significantly during OC [ F(3,33.8) = 3.2, p = 0.036], with significant inter-session difference, lower in session 2 than in session 1 ( p = 0.019) and lower in session 4 than in session 1 ( p = 0.007). The ABR wave V absolute latency changed significantly during OC [ F(3,33) = 3.3, p = 0.03], longer in the late follicular phase. There was also a significant positive correlation of TEOAEs and ABR (wave V latency and III–V interval) and significant negative correlation of MOC suppression with oestradiol levels in the follicular phase. The results of this study reflect very small changes in auditory function during OC, and they are suggestive of an increased hearing sensitivity around the time of ovulation.

Reflex control of the human inner ear: a half-octave offset in medial efferent feedback that is consistent with an efferent role in the control of masking.

The high sensitivity and frequency selectivity of the mammalian cochlea is due to amplification produced by outer hair cells (OHCs) and controlled by medial olivocochlear (MOC) efferents. Data from animals led to the view that MOC fibers provide frequency-specific inhibitory feedback; however, these studies did not measure intact MOC reflexes. To test whether MOC inhibition is primarily at the frequency that elicits the MOC activity, acoustically elicited MOC effects were quantified in humans by the change in otoacoustic emissions produced by 60-dB SPL tone and half-octave-band noise elicitors at different frequencies relative to a 40-dB SPL, 1-kHz probe tone. On average, all elicitors produced MOC effects that were skewed (elicitor frequencies -1 octave below the probe produced larger effects than those -1 octave above). The largest MOC effects were from elicitors below the probe frequency for contra- and bilateral elicitors but were from elicitors centered at the probe frequency for ipsilateral elicitors. Typically, ipsilateral elicitors produced larger effects than contralateral elicitors and bilateral elicitors produced effects near the ipsi+contra sum. Elicitors at levels down to 30-dB SPL produced similar patterns. Tuning curves (TCs) interpolated from these data were V-shaped with Q10s approximately 2. These are sharper than MOC-fiber TCs found near 1 kHz in cats and guinea pigs. Because cochlear amplification is skewed (more below the best frequency of a cochlear region), these data are consistent with an anti-masking role of MOC efferents that reduces masking by reducing the cochlear amplification seen at 1 kHz.

Test eferentny ślimaka – czułość i swoistość metody

The amplitude of click evoked otoacoustic emissions can be suppressed (reduced) with contralateral acoustic stimulation (CAS). This is thought to be due to the inhibitory control that the medial efferent auditory nerve exerts on outer hair cell function. One commonly used test of medial olivocochlear (MOC) function in humans involves measuring the degree of suppression of ipsilateral otoacoustic emissions (OAEs) by CAS. This effect is called contralateral suppression, efferent effect or olivocochlear reflex. Aim of the study. The objective of this study was to measure cut-off level of contralateral suppression, sensitivity and specificity of the efferent test. To evaluate the function of MOC system click evoked otoacoustic emissions (CEOAEs) with and without continuous contralateral broadband noise (BBN) stimulation were recorded in 14 patients with multiple sclerosis, 16 patients with unilateral cerebello-pontine angle tumor and control group matched for age and gender. BBN was presented at 50 dB SL and otoacoustic emissions were recorded in response to nonlinear clicks at 70 +/− 3 dB SPL. The cut-off level was established at −1.4 dB. For 1.4 dB cut-off level of contralateral suppression the sensitivity of the efferent test was 90% and specificity was 70%. To conclude, assessment of efferent suppression may be a useful addition to the battery test employed in the investigation of multiple sclerosis and cerebello-pontine angle tumors. The MOC suppression test may provide a tool for an early diagnosis of the brainstem pathology.