Auditory Research publications

The auditory cortex is an essential center for sound localization. In echolocating bats, combination sensitive neurons tuned to specific delays between call emission and echo perception represent target distance. In many bats, these neurons are organized as a chronotopically organized map of echo delay. However, it is still unclear to what extend these neurons can process directional information and thereby form a three-dimensional representation of space. We investigated the representation of three-dimensional space in the auditory cortex of Phyllostomus discolor. Specifically, we hypothesized that combination sensitive neurons encoding target distance in the AC can also process directional information. We used typical echolocation pulses of P. discolor combined with simulated echoes from different positions in virtual 3D-space and measured the evoked neuronal responses in the AC of the anesthetized bats. Our results demonstrate that combination sensitive neurons in the AC responded selectively to specific positions in 3-D space. While these neurons were sharply tuned to echo delay and formed a precise target distance map, the neurons' specificity in azimuth and elevation depended on the presented sound pressure level. Our data further reveal a topographic distribution of best elevation of the combination sensitive neurons along the rostro-caudal axis i.e., neurons in the rostral part of the target distance map representing short delays prefer elevations below the horizon. Due to their spatial directionality and selectivity to specific echo delays representing target distance, combination sensitive cortical neurons are suited to encode three-dimensional spatial information.

In tonal languages, such as Mandarin Chinese, the pitch contour of vowels discriminates lexical meaning, which is not the case in non-tonal languages such as German. Recent data provide evidence that pitch processing is influenced by language experience. However, there are still many open questions concerning the representation of such phonological and language-related differences at the level of the auditory cortex (AC). Using magnetoencephalography (MEG), we recorded transient and sustained auditory evoked fields (AEF) in native Chinese and German speakers to investigate language related phonological and semantic aspects in the processing of acoustic stimuli. AEF were elicited by spoken meaningful and meaningless syllables, by vowels, and by a French horn tone. Speech sounds were recorded from a native speaker and showed frequency-modulations according to the pitch-contours of Mandarin. The sustained field (SF) evoked by natural speech signals was significantly larger for Chinese than for German listeners. In contrast, the SF elicited by a horn tone was not significantly different between groups. Furthermore, the SF of Chinese subjects was larger when evoked by meaningful syllables compared to meaningless ones, but there was no significant difference regarding whether vowels were part of the Chinese phonological system or not. Moreover, the N100m gave subtle but clear evidence that for Chinese listeners other factors than purely physical properties play a role in processing meaningful signals. These findings show that the N100 and the SF generated in Heschl's gyrus are influenced by language experience, which suggests that AC activity related to specific pitch contours of vowels is influenced in a top-down fashion by higher, language related areas. Such interactions are in line with anatomical findings and neuroimaging data, as well as with the dual-stream model of language of Hickok and Poeppel that highlights the close and reciprocal interaction between superior temporal gyrus and sulcus.

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.

Sound stimuli are characterized by their rich spectral and temporal dynamic properties. Individual neurons in auditory cortex (ACX) encode both spectral and temporal aspects of sounds e.g. sound onset and/or offset. While the different fields of the ACX show gradients of frequency selectivity the large-scale organization of sound dynamics is unknown. We used widefield imaging of GCaMP6s in awake mouse ACX combined with a novel unsupervised image segmentation technique to investigate the spatiotemporal representation of sound onset and offset. Using this technique, we identified known auditory fields but also detected novel ACX areas. Furthermore, we found that ACX areas differed in their responses to tone onset and offset. Multiple areas were preferentially activated by tone offset, and on-response areas were more spatially localized than off-response areas. We also found tonotopy in off-responses. Together our results demonstrate a different spatial distribution of neurons across ACX for processing sound onsets versus offsets.

Xeroderma pigmentosum (XP) is a rare recessive heredity disease caused by DNA repair impairment characterized by photosensitivity and neurologic symptoms in half of the cases. There are eight subtypes of XP: XP-A-XP-G and XP variant. Among eight subtypes, XP complementation group A (XP-A) display the lowest DNA repair ability and the severest cutaneous and neurologic symptoms. While its pathogenesis of skin symptoms have been well-studied, that of neurological symptoms, including sensorineural hearing loss (SNHL) remains unknown. Basic studies have suggested that SNHL may be caused by inner ear damage, including damage to the spiral ganglion neurons and organ of Corti, and that the XP-A is associated with most severe form of SNHL in humans. Here, we report the occurrence of SNHL in Xpa-deficient mice. Xpa-deficient mice and wild-type mice underwent measurements for auditory brainstem response, and the results revealed that Xpa-deficient mice exhibited significantly greater (p < 0.01) ABR thresholds at 4, 8, and 16 kHz than the wild-type mice. Furthermore, the number of spiral ganglion neurons was reduced in Xpa-deficient mice compared with that in wild-type mice, indicating that hearing loss may be related to spiral ganglion neuron deficiency, consistent with the few reports published in human patients with XP. These results provide important insights into the pathogenesis of SNHL in patients with XP-A.

Onsets of acoustic stimuli are salient transients and are relevant in humans for the perception of music and speech. Previous studies of onset-duration discrimination and matching focused on whether onsets are perceived categorically. In this study, we address two issues. First, we revisit onset-duration matching and measure, for 79 conditions, how accurately and precisely human listeners can adjust the onset duration of a comparison stimulus to subjectively match that of a standard stimulus. Second, we explore measures for quantifying performance in this and other matching tasks. The conventional measures of accuracy and precision are defined by arithmetic descriptive statistics and the Euclidean distance function on the real numbers. We propose novel measures based on geometric descriptive statistics and the log-ratio distance function, the Euclidean distance function on the positive-real numbers. Only these properly account for the fact that the magnitude of onset durations, like the magnitudes of most physical quantities, can attain only positive real values. The conventional (arithmetic) measures possess a convexity bias that yields errors that grow with the width of the distribution of matches. This convexity bias leads to misrepresentations of the constant error and could even imply the existence of perceptual illusions where none exist. This is not so for the proposed (geometric) measures. We collected up to 68 matches from a given listener for each condition (about 34,000 matches in total) and examined inter-listener variability and the effects of onset duration, plateau duration, sound level, carrier, and restriction of the range of adjustable comparison stimuli on measures of accuracy and precision. Results obtained with the conventional measures generally agree with those reported in the literature. The variance across listeners is highly heterogeneous for the conventional measures but is homogeneous for the proposed measures. Furthermore, the proposed measures show that listeners tend to under- rather than to overestimate the onset duration of the comparison stimuli. They further reveal effects of the stimulus carrier on accuracy and precision which are missed by the conventional measures. Our results have broad implications for psychophysical studies that use arithmetic measures to quantify performance when geometric measures should instead be used.

Cortical entrainment of the auditory cortex to the broadband temporal envelope of a speech signal is crucial for speech comprehension. Entrainment results in phases of high and low neural excitability, which structure and decode the incoming speech signal. Entrainment to speech is strongest in the theta frequency range (4–8 Hz), the average frequency of the speech envelope. If a speech signal is degraded, entrainment to the speech envelope is weaker and speech intelligibility declines. Besides perceptually evoked cortical entrainment, transcranial alternating current stimulation (tACS) entrains neural oscillations by applying an electric signal to the brain. Accordingly, tACS-induced entrainment in auditory cortex has been shown to improve auditory perception. The aim of the current study was to modulate speech intelligibility externally by means of tACS such that the electric current corresponds to the envelope of the presented speech stream (i.e., envelope-tACS). Participants performed the Oldenburg sentence test with sentences presented in noise in combination with envelope-tACS. Critically, tACS was induced at time lags of 0 to 250 ms in 50-ms steps relative to sentence onset (auditory stimuli were simultaneous to or preceded tACS). We performed single-subject sinusoidal, linear, and quadratic fits to the sentence comprehension performance across the time lags. We could show that the sinusoidal fit described the modulation of sentence comprehension best. Importantly, the average frequency of the sinusoidal fit was 5.12 Hz, corresponding to the peaks of the amplitude spectrum of the stimulated envelopes. This finding was supported by a significant 5-Hz peak in the average power spectrum of individual performance time series. Altogether, envelope tACS modulates intelligibility of speech in noise, presumably by enhancing and disrupting (time lag with in-or out-of-phase stimulation, respectively) cortical entrainment to the speech envelope in auditory cortex.

In active sensing, animals make motor adjustments to match sensory inputs to specialized neural circuitry. Here, we describe an active sensing system for sound level processing. The pallid bat uses downward frequency-modulated (FM) sweeps as echolocation calls for general orientation and obstacle avoidance. The bat’s auditory cortex contains a region selective for these FM sweeps (FM sweep-selective region, FMSR). We show that the vast majority of FMSR neurons are sensitive and strongly selective for relatively low levels (30-60 dB SPL). Behavioral testing shows that when a flying bat approaches a target, it reduces output call levels to keep echo levels between ∼30 and 55 dB SPL. Thus, the pallid bat behaviorally matches echo levels to an optimized neural representation of sound levels. FMSR neurons are more selective for sound levels of FM sweeps than tones, suggesting that across-frequency integration enhances level tuning. Level-dependent timing of high-frequency sideband inhibition in the receptive field shapes increased level selectivity for FM sweeps. Together with previous studies, these data indicate that the same receptive field properties shape multiple filters (sweep direction, rate, and level) for FM sweeps, a sound common in multiple vocalizations, including human speech. The matched behavioral and neural adaptations for low-intensity echolocation in the pallid bat will facilitate foraging with reduced probability of acoustic detection by prey.

Many audio applications perform perception-based time-frequency (TF) analysis by decomposing sounds into a set of functions with good TF localization (i.e. with a small essential support in the TF domain) using TF transforms and applying psychoacoustic models of auditory masking to the transform coefficients. To accurately predict masking interactions between coefficients, the TF properties of the model should match those of the transform. This involves having masking data for stimuli with good TF localization. However, little is known about TF masking for mathematically well-localized signals. Most existing masking studies used stimuli that are broad in time and/or frequency and few studies involved TF conditions. Consequently, the present study had two goals. The first was to collect TF masking data for well-localized stimuli in humans. Masker and target were 10-ms Gaussian-shaped sinusoids with a bandwidth of approximately one critical band. The overall pattern of results is qualitatively similar to existing data for long maskers. To facilitate implementation in audio processing algorithms, a dataset provides the measured TF masking function. The second goal was to assess the potential effect of auditory efferents on TF masking using a modeling approach. The temporal window model of masking was used to predict present and existing data in two configurations: (1) with standard model parameters (i.e. without efferents), (2) with cochlear gain reduction to simulate the activation of efferents. The ability of the model to predict the present data was quite good with the standard configuration but highly degraded with gain reduction. Conversely, the ability of the model to predict existing data for long maskers was better with than without gain reduction. Overall, the model predictions suggest that TF masking can be affected by efferent (or other) effects that reduce cochlear gain. Such effects were avoided in the experiment of this study by using maximally-compact stimuli.

With their essential role in inner ear function, stereocilia of sensory hair cells demonstrate the importance of cellular actin protrusions. Actin packing in stereocilia is mediated by cross-linkers of the plastin, fascin, and espin families. Although mice lacking espin (ESPN) have no vestibular or auditory function, we found that mice that either lacked plastin 1 (PLS1) or had nonfunctional fascin 2 (FSCN2) had reduced inner ear function, with double-mutant mice most strongly affected. Targeted mass spectrometry indicated that PLS1 was the most abundant cross-linker in vestibular stereocilia and the second most abundant protein overall; ESPN only accounted for ∼15% of the total cross-linkers in bundles. Mouse utricle stereocilia lacking PLS1 were shorter and thinner than wild-type stereocilia. Surprisingly, although wild-type stereocilia had random liquid packing of their actin filaments, stereocilia lacking PLS1 had orderly hexagonal packing. Although all three cross-linkers are required for stereocilia structure and function, PLS1 biases actin toward liquid packing, which allows stereocilia to grow to a greater diameter.

Tonotopic map plasticity in the adult auditory cortex (AC) is a well established and oft-cited measure of auditory associative learning in classical conditioning paradigms. However, its necessity as an enduring memory trace has been debated, especially given a recent finding that the areal expansion of core AC tuned to a newly relevant frequency range may arise only transiently to support auditory learning. This has been reinforced by an ethological paradigm showing that map expansion is not observed for ultrasonic vocalizations (USVs) or for ultrasound frequencies in postweaning dams for whom USVs emitted by pups acquire behavioral relevance. However, whether transient expansion occurs during maternal experience is not known, and could help to reveal the generality of cortical map expansion as a correlate for auditory learning. We thus mapped the auditory cortices of maternal mice at postnatal time points surrounding the peak in pup USV emission, but found no evidence of frequency map expansion for the behaviorally relevant high ultrasound range in AC. Instead, regions tuned to low frequencies outside of the ultrasound range show progressively greater suppression of activity in response to the playback of ultrasounds or pup USVs for maternally experienced animals assessed at their pups’ postnatal day 9 (P9) to P10, or postweaning. This provides new evidence for a lateral-band suppression mechanism elicited by behaviorally meaningful USVs, likely enhancing their population-level signal-to-noise ratio. These results demonstrate that tonotopic map enlargement has limits as a construct for conceptualizing how experience leaves neural memory traces within sensory cortex in the context of ethological auditory learning.

Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL.

In the auditory system, early neural stations such as brain stem are characterized by strict tonotopy, which is used to deconstruct sounds to their basic frequencies. But higher along the auditory hierarchy, as early as primary auditory cortex (A1), tonotopy starts breaking down at local circuits. Here, we studied the response properties of both excitatory and inhibitory neurons in the auditory cortex of anesthetized mice. We used in vivo two photon-targeted cell-attached recordings from identified parvalbumin-positive neurons (PVNs) and their excitatory pyramidal neighbors (PyrNs). We show that PyrNs are locally heterogeneous as characterized by diverse best frequencies, pairwise signal correlations, and response timing. In marked contrast, neighboring PVNs exhibited homogenous response properties in pairwise signal correlations and temporal responses. The distinct physiological microarchitecture of different cell types is maintained qualitatively in response to natural sounds. Excitatory heterogeneity and inhibitory homogeneity within the same circuit suggest different roles for each population in coding natural stimuli.

The occurrence of tinnitus can be linked to hearing loss in the majority of cases, but there is nevertheless a large degree of unexplained heterogeneity in the relation between hearing loss and tinnitus. Part of the problem might be that hearing loss is usually quantified in terms of increased hearing thresholds, which only provides limited information about the underlying cochlear damage. Moreover, noise exposure that does not cause hearing threshold loss can still lead to "hidden hearing loss" (HHL), i.e., functional deafferentation of auditory nerve fibers (ANFs) through loss of synaptic ribbons in inner hair cells. While it is known that increased hearing thresholds can trigger increases in spontaneous neural activity in the central auditory system, i.e., a putative neural correlate of tinnitus, the central effects of HHL have not yet been investigated. Here, we exposed mice to octave-band noise at 100 and 105 dB SPL to generate HHL and permanent increases of hearing thresholds, respectively. Deafferentation of ANFs was confirmed through measurement of auditory brainstem responses and cochlear immunohistochemistry. Acute extracellular recordings from the auditory midbrain (inferior colliculus) demonstrated increases in spontaneous neuronal activity (a putative neural correlate of tinnitus) in both groups. Surprisingly, the increase in spontaneous activity was most pronounced in the mice with HHL, suggesting that the relation between hearing loss and neuronal hyperactivity might be more complex than currently understood. Our computational model indicated that these differences in neuronal hyperactivity could arise from different degrees of deafferentation of low-threshold ANFs in the two exposure groups. Our results demonstrate that HHL is sufficient to induce changes in central auditory processing, and they also indicate a non-monotonic relationship between cochlear damage and neuronal hyperactivity, suggesting an explanation for why tinnitus might occur without obvious hearing loss and conversely why hearing loss does not always lead to tinnitus.

The ear is the organ that is most sensitive to blast overpressure and ear damage is most frequently seen after blast exposure. Blast overpressure to the ear results in sensorineural hearing loss, which is untreatable and is often associated with a decline in the quality of life. In this study, we used a rat model to demonstrate the pathophysiological and structural changes in the inner ear that replicate pure sensorineural hearing loss associated with blast injury using laser-induced shock wave (LISW) without any conductive hearing loss. Our results indicate that threshold elevation of the auditory brainstem response (ABR) after blast exposure was primarily caused by outer hair cell dysfunction induced by stereociliary bundle disruption. The bundle disruption pattern was unique; disturbed stereocilia were mostly observed in the outermost row, whereas those in the inner and middle rows stereocilia remained intact. In addition, the ABR examination showed a reduction in wave I amplitude without elevation of the threshold in the lower energy exposure group. This phenomenon was caused by loss of the synaptic ribbon. This type of hearing dysfunction has recently been described as hidden hearing loss caused by cochlear neuropathy, which is associated with tinnitus or hyperacusis.

The role of source properties in across-formant integration was explored using three-formant (F1+F2+F3) analogues of natural sentences (targets). In experiment 1, F1+F3 were harmonic analogues (H1+H3) generated using a monotonous buzz source and second-order resonators; in experiment 2, F1+F3 were tonal analogues (T1+T3). F2 could take either form (H2 or T2). Target formants were always presented monaurally; the receiving ear was assigned randomly on each trial. In some conditions, only the target was present; in others, a competitor for F2 (F2C) was presented contralaterally. Buzz-excited or tonal competitors were created using the time-reversed frequency and amplitude contours of F2. Listeners must reject F2C to optimize keyword recognition. Whether or not a competitor was present, there was no effect of source mismatch between F1+F3 and F2. The impact of adding F2C was modest when it was tonal but large when it was harmonic, irrespective of whether F2C matched F1+F3. This pattern was maintained when harmonic and tonal counterparts were loudness-matched (experiment 3). Source type and competition, rather than acoustic similarity, governed the phonetic contribution of a formant. Contrary to earlier research using dichotic targets, requiring across-ear integration to optimize intelligibility, H2C was an equally effective informational masker for H2 as for T2.

Target speaker identification is essential for speech enhancement algorithms in assistive devices aimed toward helping the hearing impaired. Several recent studies have reported that target speaker identification is possible through electroencephalography (EEG) recordings. If the EEG system could be reduced to acceptable size while retaining the signal quality, hearing aids could benefit from the integration with concealed EEG. To compare the performance of a multichannel around-the-ear EEG system with high-density cap EEG recordings an envelope tracking algorithm was applied in a competitive speaker paradigm. The data from 20 normal hearing listeners were concurrently collected from the traditional state-of-the-art laboratory wired EEG system and a wireless mobile EEG system with two bilaterally-placed around-the-ear electrode arrays (cEEGrids). The results show that the cEEGrid ear-EEG technology captured neural signals that allowed the identification of the attended speaker above chance-level, with 69.3% accuracy, while cap-EEG signals resulted in the accuracy of 84.8%. Further analyses investigated the influence of ear-EEG signal quality and revealed that the envelope tracking procedure was unaffected by variability in channel impedances. We conclude that the quality of concealed ear-EEG recordings as acquired with the cEEGrid array has potential to be used in the brain-computer interface steering of hearing aids.

In the cochlea of the mustached bat, cochlear resonance produces extremely sharp frequency tuning to the dominant frequency of the echolocation calls, around 61 kHz. Such high frequency resolution in the cochlea is accomplished at the expense of losing temporal resolution because of cochlear ringing, an effect that is observable not only in the cochlea but also in the cochlear nucleus. In the midbrain, the duration of sounds is thought to be analyzed by duration-tuned neurons, which are selective to both stimulus duration and frequency. We recorded from 57 DTNs in the auditory midbrain of the mustached bat to assess if a spectral-temporal trade-off is present. Such spectral-temporal trade-off is known to occur as sharp tuning in the frequency domain which results in poorer resolution in the time domain, and vice versa. We found that a specialized sub-population of midbrain DTNs tuned to the bat’s mechanical cochlear resonance frequency escape the cochlear spectral-temporal trade-off. We also show evidence that points towards an underlying neuronal inhibition that appears to be specific only at the resonance frequency.

Acoustic overstimulation traumatizes the cochlea, resulting in auditory dysfunction. As a consequence of acoustic injury, the immune system in the cochlea is activated, leading to the production of inflammatory mediators and the infiltration of immune cells. However, the molecular mechanisms responsible for initiating these immune responses remain unclear. Here, we investigate the functional role of Toll-like receptor 4 (Tlr4), a cellular receptor that activates the innate immune system, in the regulation of cochlear responses to acoustic overstimulation. Using a Tlr4 knockout mouse model, we examined how Tlr4 deficiency affects sensory cell pathogenesis, auditory dysfunction and cochlear immune activity. We demonstrate that Tlr4 knockout does not affect sensory cell viability under physiological conditions, but reduces the level of sensory cell damage and cochlear dysfunction after acoustic injury. Together, these findings suggest that Tlr4 promotes sensory cell degeneration and cochlear dysfunction after acoustic injury. Acoustic injury provokes a site-dependent inflammatory response in both the organ of Corti and the tissues of the lateral wall and basilar membrane. Tlr4 deficiency affects these inflammatory responses in a site-dependent manner. In the organ of Corti, loss of Tlr4 function suppresses the production of interleukin 6 (Il6), a pro-inflammatory molecule, after acoustic injury. By contrast, the production of inflammatory mediators, including Il6, persists in the lateral wall and basilar membrane. In addition to immune molecules, Tlr4 knockout inhibits the expression of major histocompatibility complex class II, an antigen-presenting molecule, in macrophages, suggesting that Tlr4 participates in the antigen-presenting function of macrophages after acoustic trauma. Together, these results suggest that Tlr4 regulates multiple aspects of the immune response in the cochlea and contributes to cochlear pathogenesis after acoustic injury.

Background and objective: The auditory efferent system is a complex network of descending pathways, which mainly originate in the primary auditory cortex and are directed to several auditory subcortical nuclei. These descending pathways are connected to olivocochlear neurons, which in turn make synapses with auditory nerve neurons and outer hair cells (OHC) of the cochlea. The olivocochlear function can be studied using contralateral acoustic stimulation, which suppresses auditory nerve and cochlear responses. In the present work, we tested the proposal that the corticofugal effects that modulate the strength of the olivocochlear reflex on auditory nerve responses are produced through cholinergic synapses between medial olivocochlear (MOC) neurons and OHCs via alpha-9/10 nicotinic receptors. Methods: We used wild type (WT) and alpha-9 nicotinic receptor knock-out (KO) mice, which lack cholinergic transmission between MOC neurons and OHC, to record auditory cortex evoked potentials and to evaluate the consequences of auditory cortex electrical microstimulation in the effects produced by contralateral acoustic stimulation on auditory brainstem responses (ABR). Results: Auditory cortex evoked potentials at 15 kHz were similar in WT and KO mice. We found that auditory cortex microstimulation produces an enhancement of contralateral noise suppression of ABR waves I and III in WT mice but not in KO mice. On the other hand, corticofugal modulations of wave V amplitudes were significant in both genotypes. Conclusion: These findings show that the corticofugal modulation of contralateral acoustic suppressions of auditory nerve (ABR wave I) and superior olivary complex (ABR wave III) responses are mediated through MOC synapses.