Olivocochlear Bundle Research Articles

Chapter 29 - Cochlea and auditory nerve

The transduction process in the cochlea requires patent hair cells. Population responses that reflect this patency are the cochlear microphonic (CM) and summating potential (SP). They can be measured using electrocochleography (ECochG). The CM reflects the sound waveform in the form of outer hair cell (OHC) depolarization and hyperpolarization, and the SP reflects the average voltage difference of the OHC membrane potential for depolarization and hyperpolarization. The CM can be measured using ECochG or via the so-called otoacoustic emissions, using a sensitive microphone in the ear canal. Neural population responses are called the compound action potentials (CAPs), which by frequency selective masking can be decomposed into narrow-band action potentials (NAPs) reflecting CAPs evoked by activity from small cochlear regions. Presence of CM and absence of CAPs are the diagnostic hallmarks of auditory neuropathy. Increased and prolonged SPs are often found in Ménière's disease but are too often in the normal range to be diagnostic. When including NAP waveforms, Ménière's disease can be differentiated from vestibular schwannomas, which often feature overlapping symptoms such as dizziness, hearing loss, and tinnitus. The patency of the efferent system, particularly the olivocochlear bundle, can be tested using the suppressive effect of contralateral stimulation on the otoacoustic emission amplitude.

Effect of levodopa on cochlear mechanics and efferent auditory system of Parkinson's disease individuals.

To evaluate the effect of levodopa on cochlear dynamics and on the medial olivocochlear efferent pathway of idiopathic Parkinson's disease (PD) individuals. Individuals with and without PD, followed at a University Hospital, were submitted to Distortion Product Otoacoustic Emissions (DPOAE) and DPOAE Inhibitory Effect (OAEIE) in the presence of contralateral noise. Correlation measures between DPOAE and OAEIE results with Hoehn&Yahr (H&Y) stage, daily dose of levodopa and PD diagnosis period were established. Furthermore, electroacoustic measures were compared between individuals without and those with PD, stratified by dose of levodopa daily administered. Weak negative correlation between DPOAE amplitude and daily dose of levodopa was found, as well positive correlations between EIEOA with daily dose of levodopa and time of PD diagnosis, respectively. Higher DPOAE amplitude was found in individuals with PD using daily doses of levodopa ≤ 600 milligrams when compared to individuals without PD and those with PD using higher doses. EIEOA was lower in individuals using doses ≤ 600 milligrams, when compared to the other groups. Daily doses of levodopa up to 600 mg / day increase the cochlear mechanical-transducer responses in 2 and 3 kHz frequencies, while the action of olivocochlear efferent systems is reduced in this region.

Olivocochlear system plasticity in response to chronic noise

Plasticity in the medial and lateral olivocochlear (MOC and LOC) systems in response to chronic exposure to background noise was investigated. Three different age-groups of young mice were exposed to the same chronic moderate noise conditions with either immediate tissue harvest or harvest following restoration to quiet conditions, with age matched controls. Cochleae were dissected and standard immunohistochemistry protocols were used to label hair cells with antibodies against myosin 6 and olivocochlear synaptic terminals with synaptic vesicle protein 2 (SV2). Specimens were imaged using confocal microscopy, and density of SV2 labeling was quantified. There was no statistically significant difference in MOC SV2 density between mice raised in noise and age matched controls for any group. However, there was a statistically significant increase in LOC SV2 density for adult mice raised in noise, particularly at higher frequency regions. This could suggest a protective upregulation of the efferent system against chronic moderate noise exposure. The increase in LOC innervation persisted for juvenile mice raised in noise with subsequent restoration to quiet conditions. These data suggest that the LOC system demonstrates sound-dependent plasticity, but that synaptic morphology may be altered for a substantial time period after exposure to noise ceases.

Quantitative distribution of choline acetyltransferase activity in rat trapezoid body

There is evidence for a function of acetylcholine in the cochlear nucleus, primarily in a feedback, modulatory effect on auditory processing. Using a microdissection and quantitative microassay approach, choline acetyltransferase activity was mapped in the trapezoid bodies of rats, in which the activity is relatively higher than in cats or hamsters. Maps of series of sections through the trapezoid body demonstrated generally higher choline acetyltransferase activity rostrally than caudally, particularly in its portion ventral to the medial part of the spinal trigeminal tract. In the lateral part of the trapezoid body, near the cochlear nucleus, activities tended to be higher in more superficial portions than in deeper portions. Calculation of choline acetyltransferase activity in the total trapezoid body cross-section of a rat with a comprehensive trapezoid body map gave a value 3–4 times that estimated for the centrifugal labyrinthine bundle, which is mostly composed of the olivocochlear bundle, in the same rat. Comparisons with other rats suggest that the ratio may not usually be this high, but it is still consistent with our previous results suggesting that the centrifugal cholinergic innervation of the rat cochlear nucleus reaching it via a trapezoid body route is much higher than that reaching it via branches from the olivocochlear bundle. The higher choline acetyltransferase activity rostrally than caudally in the trapezoid body is consistent with evidence that the centrifugal cholinergic innervation of the cochlear nucleus derives predominantly from locations at or rostral to its anterior part, in the superior olivary complex and pontomesencephalic tegmentum.

Efferent Inhibition of the Cochlea.

Cholinergic efferent neurons originating in the brainstem innervate the acoustico-lateralis organs (inner ear, lateral line) of vertebrates. These release acetylcholine (ACh) to inhibit hair cells through activation of calcium-dependent potassium channels. In the mammalian cochlea, ACh shunts and suppresses outer hair cell (OHC) electromotility, reducing the essential amplification of basilar membrane motion. Consequently, medial olivocochlear neurons that inhibit OHCs reduce the sensitivity and frequency selectivity of afferent neurons driven by cochlear vibration of inner hair cells (IHCs). The cholinergic synapse on hair cells involves an unusual ionotropic ACh receptor, and a near-membrane postsynaptic cistern. Lateral olivocochlear (LOC) neurons modulate type I afferents by still-to-be-defined synaptic mechanisms. Olivocochlear neurons can be activated by a reflex arc that includes the auditory nerve and projections from the cochlear nucleus. They are also subject to modulation by higher-order central auditory interneurons. Through its actions on cochlear hair cells, afferent neurons, and higher centers, the olivocochlear system protects against age-related and noise-induced hearing loss, improves signal coding in noise under certain conditions, modulates selective attention to sensory stimuli, and influences sound localization.

Adversarial relationship between combined medial olivocochlear (MOC) and middle-ear-muscle (MEM) reflexes and alarm-in-noise detection thresholds under negative signal-to-noise ratios (SNRs)

The role of auditory efferent feedback from the medial olivocochlear system (MOCS) and the middle-ear-muscle (MEM) reflex in tonal detection tasks for humans in the presence of noise is not clearly understood. Past studies have yielded inconsistent results on the relationship between efferent feedback and tonal detection thresholds. This study attempts to address this inconsistency. Fifteen human subjects with normal hearing participated in an experiment where they were asked to identify an alarm signal in the presence of 80 dBA background (pink) noise. Masked detection thresholds were estimated using the method of two-interval forced choice (2IFC). Contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs) was measured to estimate the strength of auditory efferent feedback. Subsequent correlation analysis revealed that the contralateral suppression of TEOAEs was significantly negatively correlated (r = −0.526, n = 15, p = 0.0438) with alarm-in-noise (AIN) detection thresholds under negative signal-to-noise conditions. The result implies that the stronger the auditory efferent feedback, the worse the detection thresholds and thus the poorer the tonal detection performance in the presence of loud noise.

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.

Talking back: Development of the olivocochlear efferent system.

Developing sensory systems must coordinate the growth of neural circuitry spanning from receptors in the peripheral nervous system (PNS) to multilayered networks within the central nervous system (CNS). This breadth presents particular challenges, as nascent processes must navigate across the CNS-PNS boundary and coalesce into a tightly intermingled wiring pattern, thereby enabling reliable integration from the PNS to the CNS and back. In the auditory system, feedforward spiral ganglion neurons (SGNs) from the periphery collect sound information via tonotopically organized connections in the cochlea and transmit this information to the brainstem for processing via the VIII cranial nerve. In turn, feedback olivocochlear neurons (OCNs) housed in the auditory brainstem send projections into the periphery, also through the VIII nerve. OCNs are motor neuron-like efferent cells that influence auditory processing within the cochlea and protect against noise damage in adult animals. These aligned feedforward and feedback systems develop in parallel, with SGN central axons reaching the developing auditory brainstem around the same time that the OCN axons extend out toward the developing inner ear. Recent findings have begun to unravel the genetic and molecular mechanisms that guide OCN development, from their origins in a generic pool of motor neuron precursors to their specialized roles as modulators of cochlear activity. One recurrent theme is the importance of efferent-afferent interactions, as afferent SGNs guide OCNs to their final locations within the sensory epithelium, and efferent OCNs shape the activity of the developing auditory system. This article is categorized under: Nervous System Development > Vertebrates: Regional Development.

Otoacoustic emission suppression in children diagnosed with central auditory processing disorder and speech in noise perception deficits

ObjectiveThe present study was designed to test the hypothesis that medial olivocochlear system functionality is associated with speech recognition in babble performance in children diagnosed with central auditory processing disorder. MethodChildren diagnosed with central auditory processing disorder who specifically demonstrated speech in noise deficits were compared to children diagnosed with central auditory processing disorder without these deficits. Suppression effects were examined across 15 time intervals to examine variability. Analysis of right and left ear suppression was performed separately to evaluate laterality. Study sample52 children diagnosed with central auditory processing disorder, aged 6–14 years were divided into normal or abnormal groups based on SinB performance in each ear. Cut-off value was set at SNR = 1.33 dB. Transient otoacoustic emissions suppression was measured. ResultsThe abnormal Speech in Babble Right Ear group showed significant negative correlations with suppression levels for 7 of the 15 time intervals measured. No significant correlations with SinBR performance were observed for the remaining time intervals, as was the case for the typically evaluated R8-18 time interval and the Speech in Babble Left Ear. ConclusionsResults indicate that suppression is influenced by the time window analysed, and ear tested, and is associated with speech recognition in babble performance in children with central auditory processing disorder.

Objective assessment of subjective tinnitus through contralateral suppression of otoacoustic emissions by white noise: effects of frequency, gender, tinnitus bilaterality and age.

Accumulating evidence seems to support an association between tinnitus and medial olivocochlear bundle (MOCB) dysfunction. Most studies use patient/control comparisons to support this correlation. The aim of this study was to investigate the hypothesis in a substantially different way and evaluate the roles of gender, age, frequency and tinnitus bilaterality as possible confounding factors. The population consisted of 78 normal hearing patients with chronic tinnitus, 28 normal hearing controls, 19 presbycousic tinnitus patients and 13 presbycousic controls (n = 276 ears). Mean suppression amplitudes of transient evoked otoacoustic emissions (TEOAEs) and distortion product OAEs (DPOAEs) by contralateral white noise (50 dB SPL) were computed. Mean suppression values < 1 dB SPL or < 2 dB SPL were validated as positive test results. Overall suppression (OS) values < 1 dB SPL were qualified as a diagnostic test of moderate positive predictive value for both DPOAEs and TEOAEs, while OS values < 2 dB SPL were found to be of large negative predictive value for DPOAEs and moderate for TEOAEs. Mean suppression values (for all frequencies, OS) are of higher diagnostic value than suppression values corresponding to either lower (1-2 kHz) or higher frequencies (2.8-4 kHz for TEOAEs and 2.8-6 kHz for DPOAEs). After excluding patients with unilateral tinnitus from the analysis, correlations were found to be stronger. Useful correlations were also attributed for all age groups < 61 years. In females, OAE suppression seems to have a stronger positive predictive value, while in males it seems to have a stronger negative predictive value. OAE-based assays of MOCB function as an objective diagnostic tool for subjective tinnitus might deserve further investigation. Tinnitus uni- or bi-laterality is a confounding factor, which probably confirms the observation that defective function of the MOCB usually applies to the contralateral ear as well. Gender is an additional confounding factor, while correlations can be verified for all age groups < 61 years old.

Reflex Modification Audiometry Reveals Dual Roles for Olivocochlear Neurotransmission

Approximately 15% of American adults report some degree of difficulty hearing in a noisy environment or have auditory filtering difficulties. There are objective clinical tests of auditory filtering, yet few tests exist for mouse models that do not rely on extensive training. We have used reflex modification audiometry (RMA) and developed exclusion criteria for the mouse model. This RMA based test makes use of the acoustic startle response (ASR) and the ability of prepulses to inhibit the ASR [i.e., prepulse inhibition (PPI)] to assess the mouse's ability to detect prepulse signals presented in quiet or embedded in masking noise. We have studied PPI behavior across four inbred mouse strains with normal cochlear function and developed pre-testing exclusion criteria and test/retest reliability measures. Moreover, because both the medial (MOC) and the lateral (LOC) olivocochlear efferent feedback systems have been proposed to improve auditory behavior performance, especially in noisy backgrounds, we have examined PPI abilities in mice (with their littermate controls) either lacking the MOC receptor subunit α9 nicotinic acetylcholine receptor [α9 nAChR (–/–)] or expressing an overactive receptor [Ld'T mutation in α9 nAChR KI], or lacking an LOC efferent neuropeptide, alpha calcitonin gene-related peptide [αCGRP (–/–)] only in the CNS. Because CGRP receptor formation has been shown to mature from juvenile to adult ages, we also studied if this maturation would be reflected in PPI behavioral responses in juvenile and adult (+/+) controls and in adult αCGRP (–/–) animals. We show that 50% PPI response thresholds (sound level with 50% correct responses) in quiet are decreased in the (–/–) α9 nAChR animals, and 50% PPI responses are increased for mice with an overactive receptor (α9 nAChR KI) and are increased in adult mice lacking αCGRP (–/–). However, in background noise, only mice lacking αCGRP exhibited increased 50% PPI response thresholds, as there were no significant differences between α9 nAChR adult mouse lines and their littermate controls. These findings suggest that MOC and LOC olivocochlear neurotransmission work in tandem to improve behavioral responses to sound. These experiments further pave the way for rapid behavioral hearing assessments in other mouse models.

Effects of surgical lesions on choline acetyltransferase activity in the cat cochlea

Although it is well established that the choline acetyltransferase (ChAT, the enzyme for acetylcholine synthesis) in the mammalian cochlea is associated with its olivocochlear innervation, the distribution of this innervation in the cochlea varies somewhat among mammalian species. The quantitative distribution of ChAT activity in the cochlea has been reported for guinea pigs and rats. The present study reports the distribution of ChAT activity within the organ of Corti among the three turns of the cat cochlea and the effects of removing olivocochlear innervation either by a lateral cut aimed to totally transect the left olivocochlear bundle or a more medial cut additionally damaging the superior olivary complex on the same side. Similarly to results for guinea pig and rat, the distribution of ChAT activity in the cat outer hair cell region showed a decrease from base to apex, but, unlike in the guinea pig and rat, the cat inner hair cell region did not. As in the rat, little ChAT activity was measured in the outer supporting cell region. As previously reported for whole cat cochlea and for rat cochlear regions, transection of the olivocochlear bundle resulted in almost total loss of ChAT activity in the hair cell regions of the cat cochlea. Lesions of the superior olivary complex resulted in loss of ChAT activity in the inner hair cell region of all cochlear turns only on the lesion side but bilateral losses in the outer hair cell region of all turns. The results are consistent with previous evidence that virtually all cholinergic synapses in the mammalian cochlea are associated with its olivocochlear innervation, that the olivocochlear innervation to the inner hair cell region is predominantly ipsilateral, and that the olivocochlear innervation to the outer hair cells is bilateral.

Frequency specificity and left-ear advantage of medial olivocochlear efferent modulation: a study based on stimulus frequency otoacoustic emission.

The medial olivocochlear (MOC) bundle is an auditory nucleus that projects efferent nerve fibers to the outer hair cells (OHCs) for synaptic innervation. The aim of the present study was to investigate the possible existence of frequency and ear specificity in MOC efferent modulation, as well as how MOC activation influences cochlear tuning. Stimulus frequency otoacoustic emissions (SFOAEs) were used to study MOC efferent modulation. Therefore, the current experiment was designed to compare the degree of SFOAE suppression in the both ears of 20 individuals at 1, 2, 4, and 8 kHz. We also compared changes in Q10 values of SFOAE suppression tuning curves at 1, 2, and 4 kHz under contralateral acoustic stimulation (CAS) and no-CAS conditions. We observed a significant reduction in SFOAE magnitude in the CAS condition compared with the no-CAS condition at 1 and 2 kHz in the left ear. A significant difference in CAS suppression was also found between the left and right ears at 1 and 2 kHz, with larger CAS suppression in the left ear. CAS further produced a statistically significant increase in the Q10 value at 1 kHz and a significant reduction in Q10 values at 2 and 4 kHz. These findings suggest a left-ear advantage in terms of CAS-induced MOC efferent SFOAE suppression, with larger MOC efferent modulation for lower frequencies, and cochlear tuning was sharpened by means of MOC activation at lower frequencies and broadened at higher frequencies.

Strain-specific differences in the development of neuronal excitability in the mouse ventral nucleus of the trapezoid body

This investigation compared the development of neuronal excitability in the ventral nucleus of the trapezoid body (VNTB) between two strains of mice with differing progression rates for age-related hearing loss. In contrast to CBA/Ca (CBA) mice, the C57BL/6J (C57) strain are subject to hearing loss from a younger age and are more prone to damage from sound over-exposure. Higher firing rates in the medial olivocochlear system (MOC) are associated with protection from loud sounds and these cells are located in the VNTB. We postulated that reduced neuronal firing of the MOC in C57 mice could contribute to hearing loss in this strain by reducing efferent protection. Whole cell patch clamp was used to compare the electrical properties of VNTB neurons from the two strains initially in two age groups: before and after hearing onset at ∼ P9 and ∼P16, respectively. Prior to hearing onset VNTB neurons electrophysiological properties were identical in both strains, but started to diverge after hearing onset. One week after hearing onset VNTB neurons of C57 mice had larger amplitude action potentials but in contrast to CBA mice, their waveform failed to accelerate with increasing age, consistent with the faster inactivation of voltage-gated potassium currents in C57 VNTB neurons. The lower frequency action potential firing of C57 VNTB neurons at P16 was maintained to P28, indicating that this change was not a developmental delay. We conclude that C57 VNTB neurons fire at lower frequencies than in the CBA strain, supporting the hypothesis that reduced MOC firing could contribute to the greater hearing loss of the C57 strain.

SLC44A4 mutation causes autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss.

Clinical, genetic, and functional investigations were performed to identify the causative mutation in a distinctive Chinese family with postlingual non-syndromic mid-frequency sensorineural hearing loss. Whole-exome sequencing revealed SLC44A4, which encodes the choline transport protein, as the pathogenic gene in this family. In the zebrafish model, downregulation of slc44a4 using morpholinos led to significant abnormalities in the zebrafish inner ear and lateral line neuromasts and contributed, to some extent, to disabilities in hearing and balance. SH-SY5Y cells transfected with SLC44A4 showed higher choline uptake and acetylcholine release than that of cells transfected with mutant SLC44A4. We concluded that mutation of SLC44A4 may cause defects in the Choline- acetylcholine system, which is crucial to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury, leading to hearing loss.

Assessment of Ipsilateral Efferent Effects in Human via ECochG.

Development of electrophysiological means to assess the medial olivocochlear (MOC) system in humans is important to further our understanding of the function of that system and for the refinement and validation of psychoacoustical and otoacoustic emission methods which are thought to probe the MOC. Based on measurements in anesthetized animals it has been hypothesized that the MOC-reflex (MOCR) can enhance the response to signals in noise, and several lines of evidence support such a role in humans. A difficulty in these studies is the isolation of efferent effects. Efferent activation can be triggered by acoustic stimulation of the contralateral or ipsilateral ear, but ipsilateral stimulation is thought to be more effective. However, ipsilateral stimulation complicates interpretation of effects since these sounds can affect the perception of other ipsilateral sounds by mechanisms not involving olivocochlear efferents. We assessed the ipsilaterally evoked MOCR in human using a transtympanic procedure to record mass-potentials from the cochlear promontory or the niche of the round window. Averaged compound action potential (CAP) responses to masked probe tones of 4 kHz with and without a precursor (designed to activate the MOCR but not the stapedius reflex) were extracted with a polarity alternating paradigm. The masker was either a simultaneous narrow band noise masker or a short (20-ms) tonal ON- or OFF-frequency forward masker. The subjects were screened for normal hearing (audiogram, tympanogram, threshold stapedius reflex) and psychoacoustically tested for the presence of a precursor effect. We observed a clear reduction of CAP amplitude by the precursor, for different masking conditions. Even without an MOCR, this is expected because the precursor will affect the response to subsequent stimuli via neural adaptation. To determine whether the precursor also activated the efferent system, we measured the CAP over a range of masker levels, with or without precursor, and for different types of masker. The results show CAP reduction consistent with the type of gain reduction caused by the MOCR. These results generally support psychoacoustical paradigms designed to probe the efferent system as indeed activating the MOCR system, but not all observations are consistent with this mechanism.

Effect of efferent activation on binaural frequency selectivity

Binaural notched-noise experiments indicate a reduced frequency selectivity of the binaural system compared to monaural processing. The present study investigates how auditory efferent activation (via the medial olivocochlear system) affects binaural frequency selectivity in normal-hearing listeners. Thresholds were measured for a 1-kHz signal embedded in a diotic notched-noise masker for various notch widths. The signal was either presented in phase (diotic) or in antiphase (dichotic), gated with the noise. Stimulus duration was 25 ms, in order to avoid efferent activation due to the masker or the signal. A bandpass-filtered noise precursor was presented prior to the masker and signal stimuli to activate the efferent system. The silent interval between the precursor and the masker-signal complex was 50 ms. For comparison, thresholds for detectability of the masked signal were also measured in a baseline condition without the precursor and, in addition, without the masker. On average, the results of the baseline condition indicate an effectively wider binaural filter, as expected. For both signal phases, the addition of the precursor results in effectively wider filters, which is in agreement with the hypothesis that cochlear gain is reduced due to the presence of the precursor.

Contralateral Inhibition of Click- and Chirp-Evoked Human Compound Action Potentials.

Cochlear outer hair cells (OHC) receive direct efferent feedback from the caudal auditory brainstem via the medial olivocochlear (MOC) bundle. This circuit provides the neural substrate for the MOC reflex, which inhibits cochlear amplifier gain and is believed to play a role in listening in noise and protection from acoustic overexposure. The human MOC reflex has been studied extensively using otoacoustic emissions (OAE) paradigms; however, these measurements are insensitive to subsequent “downstream” efferent effects on the neural ensembles that mediate hearing. In this experiment, click- and chirp-evoked auditory nerve compound action potential (CAP) amplitudes were measured electrocochleographically from the human eardrum without and with MOC reflex activation elicited by contralateral broadband noise. We hypothesized that the chirp would be a more optimal stimulus for measuring neural MOC effects because it synchronizes excitation along the entire length of the basilar membrane and thus evokes a more robust CAP than a click at low to moderate stimulus levels. Chirps produced larger CAPs than clicks at all stimulus intensities (50–80 dB ppeSPL). MOC reflex inhibition of CAPs was larger for chirps than clicks at low stimulus levels when quantified both in terms of amplitude reduction and effective attenuation. Effective attenuation was larger for chirp- and click-evoked CAPs than for click-evoked OAEs measured from the same subjects. Our results suggest that the chirp is an optimal stimulus for evoking CAPs at low stimulus intensities and for assessing MOC reflex effects on the auditory nerve. Further, our work supports previous findings that MOC reflex effects at the level of the auditory nerve are underestimated by measures of OAE inhibition.

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.

Ablation of the auditory cortex results in changes in the expression of neurotransmission-related mRNAs in the cochlea

The auditory cortex (AC) dynamically regulates responses of the Organ of Corti to sound through descending connections to both the medial (MOC) and lateral (LOC) olivocochlear efferent systems. We have recently provided evidence that AC has a reinforcement role in the responses to sound of the auditory brainstem nuclei. In a molecular level, we have shown that descending inputs from AC are needed to regulate the expression of molecules involved in outer hair cell (OHC) electromotility control, such as prestin and the α10 nicotinic acetylcholine receptor (nAchR). In this report, we show that descending connections from AC to olivocochlear neurons are necessary to regulate the expression of molecules involved in cochlear afferent signaling. RT-qPCR was performed in rats at 1, 7 and 15 days after unilateral ablation of the AC, and analyzed the time course changes in gene transcripts involved in neurotransmission at the first auditory synapse. This included the glutamate metabolism enzyme glutamate decarboxylase 1 (glud1) and AMPA glutamate receptor subunits GluA2-4. In addition, gene transcripts involved in efferent regulation of type I spiral ganglion neuron (SGN) excitability mediated by LOC, such as the α7 nAchR, the D2 dopamine receptor, and the α1, and γ2 GABAA receptor subunits, were also investigated. Unilateral AC ablation induced up-regulation of GluA3 receptor subunit transcripts, whereas both GluA2 and GluA4 mRNA receptors were down-regulated already at 1 day after the ablation. Unilateral removal of the AC also resulted in up-regulation of the transcripts for α7 nAchR subunit, D2 dopamine receptor, and α1 GABAA receptor subunit at 1 day after the ablation. Fifteen days after the injury, AC ablations induced an up-regulation of glud1 transcripts.