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Age-related hearing loss is linked to cognitive impairment, but the mechanisms that relate to these conditions remain unclear. Evidence shows that the activation of medial olivocochlear (MOC) neurons delays cochlear aging and hearing loss. Consequently, the loss of MOC function may be related to cognitive impairment. The α9/α10 nicotinic receptor is the main target of cholinergic synapses between the MOC neurons and cochlear outer hair cells. Here, we explored spatial learning and memory performance in middle-aged wild-type (WT) and α9-nAChR subunit knock-out (KO) mice using the Barnes maze and measured auditory brainstem response (ABR) thresholds and the number of cochlear hair cells as a proxy of cochlear aging. Our results show non-significant spatial learning differences between WT and KO mice, but KO mice had a trend of increased latency to enter the escape box and freezing time. To test a possible reactivity to the escape box, we evaluated the novelty-induced behavior using an open field and found a tendency towards more freezing time in KO mice. There were no differences in memory, ABR threshold, or the number of cochlear hair cells. We suggest that the lack of α9-nAChR subunit alters novelty-induced behavior, but not spatial learning in middle-aged mice, by a non-cochlear mechanism.

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It is widely established that musicians possess a higher level in certain auditory perceptual abilities when compared to non-musicians. This improvement may be mediated, at least in part, by changes in the cochlear response induced by reflex activation of the olivocochlear efferent system. In this review, we describe and analyze the scientific evidence regarding possible differences in the efferent response in musicians and non-musicians. The main evidence observed is that musicians present a greater robustness of the efferent olivocochlear reflex when measured by suppression of otoacoustic emissions and compared to non-musicians. Analyzing the articles presented in this review, it is possible to point out that the differential role of the efferent effect in musicians is not yet established. There is not enough evidence to support the idea that the olivocochlear system favors comparative changes in the properties of musicians' auditory filters. New studies with psychoacoustic techniques, among others, are needed to measure the effect of the olivocochlear reflex on tuning, gain, compression, or temporal resolution in musicians and non-musicians.

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Introduction: The mechanisms underlying tinnitus perception are still under research. One of the proposed hypotheses involves an alteration in top-down processing of auditory activity. Low-frequency oscillations in the delta and theta bands have been recently described in brain and cochlear infrasonic signals during selective attention paradigms in normal hearing controls. Here, we propose that the top-down oscillatory activity observed in brain and cochlear signals during auditory and visual selective attention in normal subjects, is altered in tinnitus patients, reflecting an abnormal functioning of the corticofugal pathways that connect brain circuits with the cochlear receptor. Methods: To test this hypothesis, we used a behavioral task that alternates between auditory and visual top-down attention while we simultaneously measured electroencephalogram (EEG) and distortion-product otoacoustic emissions (DPOAE) signals in 14 tinnitus and 14 control subjects. Results: We found oscillatory activity in the delta and theta bands in cortical and cochlear channels in control and tinnitus patients. There were significant decreases in the DPOAE oscillatory amplitude during the visual attention period as compared to the auditory attention period in tinnitus and control groups. We did not find significant differences when using a between-subjects statistical approach comparing tinnitus and control groups. On the other hand, we found a significant cluster in the delta band in tinnitus when using within-group statistics to compare the difference between auditory and visual DPOAE oscillatory power. Conclusion: These results confirm the presence of top-down infrasonic low-frequency cochlear oscillatory activity in the delta and theta bands in tinnitus patients, showing that the corticofugal suppression of cochlear oscillations during visual and auditory attention in tinnitus patients is preserved.

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Abstract Introduction Distortion product otoacoustic emissions (DPOAE) and their suppression may be considered useful in monitoring cochlear function and the efferent auditory pathway inhibitory effect. Nonetheless, the establishment of reliable parameters of response variations is of great importance. Objectives To verify the replicability of test and retest in the research of the inhibitory effect of the efferent pathway using contralateral suppressing stimulus during DPOAE recording for clinical applicability. Methods Cross-sectional study with 48 volunteers, aged 18 to 30 years, with normal audiometric thresholds. The procedures included were audiometric and immittance measures to overrule any conductive or sensorineural conditions and DPOAE recordings without and with contralateral suppression with a 60 dBHL white noise. Distortion product otoacoustic emissions amplitudes were analyzed and compared in both conditions with Wilcoxon test, and the Spearman correlation test was used to assess test-retest reliability. Results The comparative analysis showed differences between amplitudes in test and retest conditions only in 1,500 Hz for DPOAE measures with all other tested frequencies showing no differences, and no difference was observed in all recorded frequencies in the test and retest comparison for DPOAE suppression. The degree of correlation between test and retest of DPOAE amplitude was good at 6,000 Hz and strong (r > 0.880) at the other frequencies. For DPOAE with suppression, all frequencies presented strong correlation between test and retest: 1,500 Hz (r = 0.880), 2,000 Hz (r = 0.882), 3,000 Hz (r = 0.940), and 6,000 Hz (r = 0.957). Conclusions The study found good replicability in contralateral suppression of DPOAE with potential clinical applicability, and we recommend conducting the test from 2000Hz to higher frequencies for more reliable results.

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Cholinergic transmission is essential for survival and reproduction, as it is involved in several physiological responses. In the auditory system, both ascending and descending auditory pathways are modulated by cholinergic transmission, affecting the perception of sounds. The auditory efferent system is a neuronal network comprised of several feedback loops, including corticofugal and brainstem pathways to the cochlear receptor. The auditory efferent system's -final and mandatory synapses that connect the brain with the cochlear receptor- involve medial olivocochlear neurons and outer hair cells. A unique cholinergic transmission mediates these synapses through α9/α10 nicotinic receptors. To study this receptor, it was generated a strain of mice carrying a null mutation of the Chrna9 gene (α9-KO mice), lacking cholinergic transmission between medial olivocochlear neurons and outer hair cells, providing a unique opportunity to study the role of medial olivocochlear cholinergic transmission in auditory and cognitive functions. In this article, we review behavioral and physiological studies carried out to research auditory efferent function in the context of audition, cognition, and hearing impairments. Auditory studies have shown that hearing thresholds in the α9-KO mice are normal, while more complex auditory functions, such as frequency selectivity and sound localization, are altered. The corticofugal pathways have been studied in α9-KO mice using behavioral tasks, evidencing a reduced capacity to suppress auditory distractors during visual selective attention. Finally, we discuss the evolutionary role of the auditory efferent system detecting vocalizations in noise and its role in auditory disorders, such as the prevention of age-related hearing loss.

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Introduction Distortion product otoacoustic emissions (DPOAE) and their suppression may be considered useful in monitoring cochlear function and the efferent auditory pathway inhibitory effect. Nonetheless, the establishment of reliable parameters of response variations is of great importance. Objectives To verify the replicability of test and retest in the research of the inhibitory effect of the efferent pathway using contralateral suppressing stimulus during DPOAE recording for clinical applicability. Methods Cross-sectional study with 48 volunteers, aged 18 to 30 years, with normal audiometric thresholds. The procedures included were audiometric and immittance measures to overrule any conductive or sensorineural conditions and DPOAE recordings without and with contralateral suppression with a 60 dBHL white noise. Distortion product otoacoustic emissions amplitudes were analyzed and compared in both conditions with Wilcoxon test, and the Spearman correlation test was used to assess test-retest reliability. Results The comparative analysis showed differences between amplitudes in test and retest conditions only in 1,500 Hz for DPOAE measures with all other tested frequencies showing no differences, and no difference was observed in all recorded frequencies in the test and retest comparison for DPOAE suppression. The degree of correlation between test and retest of DPOAE amplitude was good at 6,000 Hz and strong (r > 0.880) at the other frequencies. For DPOAE with suppression, all frequencies presented strong correlation between test and retest: 1,500 Hz (r = 0.880), 2,000 Hz (r = 0.882), 3,000 Hz (r = 0.940), and 6,000 Hz (r = 0.957). Conclusions The study found good replicability in contralateral suppression of DPOAE with potential clinical applicability, and we recommend conducting the test from 2000Hz to higher frequencies for more reliable results.

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

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Resumen Introducción: La presencia de tinnitus se asocia a un incremento del nivel de ansiedad y empeoramiento de la calidad de vida, sin embargo, aún no existe claridad de si el sistema eferente auditivo podría influir en estas relaciones. Objetivo: Determinar si las amplitudes de las emisiones otoacústicas por producto de distorsión (EOAPD) y el efecto supresor del reflejo olivococlear gatillado con ruido contralateral (ROC) se asocian al grado del impacto psicoemocional y nivel de ansiedad en pacientes con tinnitus. Material y Método: Se evaluaron las amplitudes de EOAPD y magnitud del ROC para cada oído de manera independiente en una cohorte de 32 sujetos tinnitus y 26 controles, cuyos valores fueron correlacionados con State-Trait Anxiety Inventory (STAI) y Tinnitus Handicap Inventory (THI). Resultados: Los pacientes con tinnitus tuvieron una correlación significativa entre la magnitud del ROC del oído izquierdo y los puntajes en las pruebas de STAI y THI. Conclusión: Una mayor carga de ansiedad y peor calidad de vida en sujetos con tinnitus puede estar asociada con un empeoramiento del efecto supresor del ROC de la vía eferente auditiva.

Abstract Introduction: Tinnitus is associated with an increase in the degree of anxiety and with worse quality of life. However, whether there are relations between the function of the auditory efferent system and anxiety and tinnitus distress levels is not known. Aim: To determine possible associations between the distortion product otoacoustic emission (DPOAE) amplitudes and the suppressing effect of the olivo-cochlear reflex (OCR) with anxiety and psycho-emotional impact in tinnitus. Material and Method: DPOAE amplitudes and OCR strength were evaluated for each ear independently in a cohort of 32 tinnitus and 26 controls, whose values were correlated with the State-Trait Anxiety Inventory (STAI) and Tinnitus Handicap Inventory (THI). Results: A significant correlation of STAI and THI scales with the OCR strength measured in the left ear was found in subjects with tinnitus. Conclusion: A higher anxiety load and worse quality of life in subjects with tinnitus may be associated with an impaired olivocochlear reflex suppressing effect.

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The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through olivocochlear (OC) neurons. Medial OC neurons make cholinergic synapses with outer hair cells (OHCs) through nicotinic receptors constituted by α9 and α10 subunits. One of the physiological functions of the α9 nicotinic receptor subunit (α9-nAChR) is the suppression of auditory distractors during selective attention to visual stimuli. In a recent study we demonstrated that the behavioral performance of alpha-9 nicotinic receptor knock-out (KO) mice is altered during selective attention to visual stimuli with auditory distractors since they made less correct responses and more omissions than wild type (WT) mice. As the inhibition of the behavioral responses to irrelevant stimuli is an important mechanism of the selective attention processes, behavioral errors are relevant measures that can reflect altered inhibitory control. Errors produced during a cued attention task can be classified as premature, target and perseverative errors. Perseverative responses can be considered as an inability to inhibit the repetition of an action already planned, while premature responses can be considered as an index of the ability to wait or retain an action. Here, we studied premature, target and perseverative errors during a visual attention task with auditory distractors in WT and KO mice. We found that α9-KO mice make fewer perseverative errors with longer latencies than WT mice in the presence of auditory distractors. In addition, although we found no significant difference in the number of target error between genotypes, KO mice made more short-latency target errors than WT mice during the presentation of auditory distractors. The fewer perseverative error made by α9-KO mice could be explained by a reduced motivation for reward and an increased impulsivity during decision making with auditory distraction in KO mice.

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UNLABELLED: During selective attention, subjects voluntarily focus their cognitive resources on a specific stimulus while ignoring others. Top-down filtering of peripheral sensory responses by higher structures of the brain has been proposed as one of the mechanisms responsible for selective attention. A prerequisite to accomplish top-down modulation of the activity of peripheral structures is the presence of corticofugal pathways. The mammalian auditory efferent system is a unique neural network that originates in the auditory cortex and projects to the cochlear receptor through the olivocochlear bundle, and it has been proposed to function as a top-down filter of peripheral auditory responses during attention to cross-modal stimuli. However, to date, there is no conclusive evidence of the involvement of olivocochlear neurons in selective attention paradigms. Here, we trained wild-type and α-9 nicotinic receptor subunit knock-out (KO) mice, which lack cholinergic transmission between medial olivocochlear neurons and outer hair cells, in a two-choice visual discrimination task and studied the behavioral consequences of adding different types of auditory distractors. In addition, we evaluated the effects of contralateral noise on auditory nerve responses as a measure of the individual strength of the olivocochlear reflex. We demonstrate that KO mice have a reduced olivocochlear reflex strength and perform poorly in a visual selective attention paradigm. These results confirm that an intact medial olivocochlear transmission aids in ignoring auditory distraction during selective attention to visual stimuli. SIGNIFICANCE STATEMENT: The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through the olivocochlear system. It has been proposed to function as a top-down filter of peripheral auditory responses during attention to cross-modal stimuli. However, to date, there is no conclusive evidence of the involvement of olivocochlear neurons in selective attention paradigms. Here, we studied the behavioral consequences of adding different types of auditory distractors in a visual selective attention task in wild-type and α-9 nicotinic receptor knock-out (KO) mice. We demonstrate that KO mice perform poorly in the selective attention paradigm and that an intact medial olivocochlear transmission aids in ignoring auditory distractors during attention.

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The auditory efferent system originates in the auditory cortex and projects to the medial geniculate body (MGB), inferior colliculus (IC), cochlear nucleus (CN) and superior olivary complex (SOC) reaching the cochlea through olivocochlear (OC) fibers. This unique neuronal network is organized in several afferent-efferent feedback loops including: the (i) colliculo-thalamic-cortico-collicular; (ii) cortico-(collicular)-OC; and (iii) cortico-(collicular)-CN pathways. Recent experiments demonstrate that blocking ongoing auditory-cortex activity with pharmacological and physical methods modulates the amplitude of cochlear potentials. In addition, auditory-cortex microstimulation independently modulates cochlear sensitivity and the strength of the OC reflex. In this mini-review, anatomical and physiological evidence supporting the presence of a functional efferent network from the auditory cortex to the cochlear receptor is presented. Special emphasis is given to the corticofugal effects on initial auditory processing, that is, on CN, auditory nerve and cochlear responses. A working model of three parallel pathways from the auditory cortex to the cochlea and auditory nerve is proposed.

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There are two types of sensory cells in the mammalian cochlea, inner hair cells, which make synaptic contact with auditory-nerve afferent fibers, and outer hair cells that are innervated by crossed and uncrossed medial olivocochlear (MOC) efferent fibers. Contralateral acoustic stimulation activates the uncrossed efferent MOC fibers reducing cochlear neural responses, thus modifying the input to the central auditory system. The chinchilla, among all studied mammals, displays the lowest percentage of uncrossed MOC fibers raising questions about the strength and frequency distribution of the contralateral-sound effect in this species. On the other hand, MOC effects on cochlear sensitivity have been mainly studied in anesthetized animals and since the MOC-neuron activity depends on the level of anesthesia, it is important to assess the influence of anesthesia in the strength of efferent effects. Seven adult chinchillas (Chinchilla laniger) were chronically implanted with round-window electrodes in both cochleae. We compared the effect of contralateral sound in awake and anesthetized condition. Compound action potentials (CAP) and cochlear microphonics (CM) were measured in the ipsilateral cochlea in response to tones in absence and presence of contralateral sound. Control measurements performed after middle-ear muscles section in one animal discarded any possible middle-ear reflex activation. Contralateral sound produced CAP amplitude reductions in all chinchillas, with suppression effects greater by about 1-3 dB in awake than in anesthetized animals. In contrast, CM amplitude increases of up to 1.9 dB were found in only three awake chinchillas. In both conditions the strongest efferent effects were produced by contralateral tones at frequencies equal or close to those of ipsilateral tones. Contralateral CAP suppressions for 1-6 kHz ipsilateral tones corresponded to a span of uncrossed MOC fiber innervation reaching at least the central third of the chinchilla cochlea.

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El sistema eferente auditivo está constituido por el sistema olivococlear y por vías descendentes que provienen de la corteza auditiva y se dirigen a la cóclea. El sistema olivococlear se divide en una porción medial y una lateral, con neuronas que inervan a las células ciliadas externas y a fibras del nervio auditivo respectivamente. El principal neurotransmisor de las sinapsis olivococleares es acetilcolina, y tanto las células ciliadas externas como las fibras del nervio auditivo poseen receptores para esta molécula. El sistema eferente córtico-coclear se origina en la capa V y VI de la corteza auditiva y proyecta a los colículos inferiores y complejo olivar superior, donde a través del sistema olivococlear se conecta con el órgano receptor auditivo. En este artículo se revisan importantes hallazgos obtenidos en los últimos años que involucran (i) nuevos neurotransmisores y receptores del sistema eferente auditivo; (ii) vías descendentes de la corteza auditiva y su rol fisiológico sobre las respuestas cocleares y (iii) rol del sistema eferente auditivo en patologías audiológicas y neuropsiquiátricas.

The auditory efferent system is composed by the olivocochlear fibers and descending projections that originate in the auditory cortex and end in the cochlea. The olivocochlear system is divided into a medial and lateral division, with fibers directed to the outer hair cells and to the auditory nerve fibers respectively. It is known that acetylcholine is the main neurotransmitter of the olivocochlear synapses and that outer hair cells and auditory nerve fibers have receptors to this molecule. The cortico-cochlear efferent system originates in layers V and VI of the auditory cortex. These descending projections are directed to the inferior colliculus and superior olivary complex, a site in which the olivocochlear fibers emerge and connect the brain with the cochlear receptor. In this article recent discoveries obtained in the last years are reviewed: (i) new neurotransmitters and receptors of the olivocochlear system; (ii) anatomy and physiology of descending pathways from the auditory cortex to the cochlea and, (iii) clinical role of auditory efferents in audiological and neuropsychiatric pathologies.

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