Cochlear Efferent Innervation Is Sparse in Humans and Decreases with Age

Liberman, Leslie D.; Liberman, M. Charles

doi:10.1523/jneurosci.3004-18.2019

Cited by 38 publications

(44 citation statements)

References 62 publications

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“…Moreover, as the mouse ages, there are significant changes in the efficiency of the MOC suppression mechanism as elicited by contralateral narrowband stimuli, reinforcing the idea that age-related changes in the MOC or the operating points of OHCs might play a role in the progression of presbycusis in mammals (46)(47)(48)(49)(50). A similar midcochlear distribution of efferent terminals has recently been seen in human cochlea (86). Remarkably, our work shows greater age-related apical and basal loss of OHCs in WT compared to mice with enhanced MOC feedback, suggesting that therapeutics designed to enhance the magnitude or duration of efferent effects on cochlear function could be beneficial in preventing OHC death.…”

Section: Discussionsupporting

confidence: 62%

Preventing presbycusis in mice with enhanced medial olivocochlear feedback

Boero

Castagna

Terreros

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“Growing old” is the most common cause of hearing loss. Age-related hearing loss (ARHL) (presbycusis) first affects the ability to understand speech in background noise, even when auditory thresholds in quiet are normal. It has been suggested that cochlear denervation (“synaptopathy”) is an early contributor to age-related auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics (“gain of function” nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calcium-gated potassium channels. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses. Cochlear structure was characterized in immunolabeled organ of Corti whole mounts using confocal microscopy to quantify hair cells, auditory neurons, presynaptic ribbons, and postsynaptic glutamate receptors. Aged wild-type mice had elevated acoustic thresholds and synaptic loss. Afferent synapses were lost from inner hair cells throughout the aged cochlea, together with some loss of outer hair cells. In contrast, cochlear structure and function were preserved in aged mice with gain-of-function nAChRs that provide enhanced olivocochlear inhibition, suggesting that efferent feedback is important for long-term maintenance of inner ear function. Our work provides evidence that olivocochlear-mediated resistance to presbycusis-ARHL occurs via the α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.

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Section: Discussionsupporting

confidence: 62%

Preventing presbycusis in mice with enhanced medial olivocochlear feedback

Boero

Castagna

Terreros

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…As regards the auditory periphery model itself, recent insights into the MOC reflex’s circuitry will enhance the biological realism of any future models incorporating efferent feedback. Our model and previous phenomenological models simulate efferent feedback as a solely on-frequency effect which appears unlikely given anatomical evidence that MOC neurons are sparse and innervate relatively broad regions of the cochlea [95, 96]. Additionally, most models do not include neural adaptation to stimulus statistics as a potential contributing factor to speech-in-noise discrimination [73, 79], we therefore cannot discount its involvement in the lexical-decision task.…”

Section: Discussionmentioning

confidence: 98%

Perceptual gating of a brainstem reflex facilitates speech understanding in human listeners

Hernández-Pérez

Mikiel-Hunter

McAlpine

et al. 2020

Preprint

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14Navigating "cocktail party" situations by enhancing foreground sounds over irrelevant background 15 information is typically considered from a cortico-centric perspective. However, subcortical circuits, 16 such as the medial olivocochlear reflex (MOCR) that modulates inner ear activity itself, have ample 17 opportunity to extract salient features from the auditory scene prior to any cortical processing. To 18 understand the contribution of auditory subcortical nuclei and the cochleae, physiological 19 recordings were made along the auditory pathway while listeners differentiated non(sense)-words 20 and words. Both naturally-spoken and intrinsically-noisy, vocoded speechfiltering that mimics 21 processing by a cochlear implant-significantly activated the MOCR, whereas listening to speech-22 in-background noise revealed instead engagement of midbrain and cortical resources. An auditory 23 periphery model reproduced these speech degradation-specific effects, providing a rationale for 24 goal-directed MOCR gating to enhance representation of speech features in the auditory nerve. 25These results highlight two strategies co-existing in the auditory system to accommodate 26 categorically different speech degradations. 27 78 cortical auditory responses in both the active listening task and when listeners were required to 79 ignore the task and watch a silent, non-subtitled film. 80Maintaining a fixed task difficulty across speech manipulations, we found measures of hearing 81 function at the level of the cochlea, brainstem, midbrain and cortex to be modulated differently 82 depending on the degradation type applied to speech sounds, and on whether or not speech was 83 3 actively attended. Specifically, the MOCR, assessed in terms of the magnitude of click-evoked 84 OAEs (CEOAEs), was activated by vocoded speech-an intrinsically degraded speech signal-but 85 not by otherwise 'clean' speech presented in either babble-noise or speech-shaped noise. Neural 86 activity at the first synaptic stage of central processing in the cochlear nucleus (CN)-assessed 87 physiologically through auditory brainstem responses (ABRs)-confirmed the reduction in cochlear 88 gain for actively attended vocoded speech, but not speech-in-noise. Conversely, neural activity 89 generated by the auditory midbrain was significantly increased in active vs. passive listening for 90 speech in babble and speech-shaped noise, but not for vocoded speech. This increase was 91 associated with elevated cortical markers of listening effort for the speech-in-noise conditions. A 92 model of the auditory periphery including an MOC circuit with biophysically-realistic temporal 93 dynamics confirmed the stimulus-dependent role of the MOCR in enhancing neural coding of 94 speech signals. Our data suggest that otherwise identical performance in active listening tasks may 95 invoke quite different efferent circuits, requiring different levels of listening effort, depending on the 96 type of stimulus degradation experienced. 98 Results 99Iso-performance in three manipul...

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“…Unfortunately, there is currently no way to investigate the cochlear effects of LOC dysfunction noninvasively in humans (Groff & Liberman, 2003;Le Prell et al, 2003). Regarding MOC efferents, previous studies have demonstrated that the density of cholinergic neurons peaks in the upper basal turn, corresponding to the 4000-Hz area in humans, and decreases toward the apex and base (L. D. Liberman & Liberman, 2019;M. C. Liberman & Gao, 1995).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Parkinson's Disease on Otoacoustic Emissions and Efferent Suppression of Transient Evoked Otoacoustic Emissions

Groote

Bockstael

Botteldooren

et al. 2021

J Speech Lang Hear Res

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Purpose Several studies have demonstrated increased auditory thresholds in patients with Parkinson's disease (PD) based on subjective tonal audiometry. However, the pathophysiological mechanisms underlying auditory dysfunction in PD remain elusive. The primary aim of this study was to investigate cochlear and olivocochlear function in PD using objective measurements and to assess the effect of dopaminergic medication on auditory function. Method Eighteen patients with PD and 18 gender- and age-matched healthy controls (HCs) were included. Patients with PD participated in medication on and off conditions. Linear mixed models were used to determine the effect of PD on tonal audiometry, transient evoked and distortion product otoacoustic emissions (OAEs), and efferent suppression (ES). Results Tonal audiometry revealed normal auditory thresholds in patients with PD for their age across all frequencies. OAE signal amplitudes demonstrated a significant interaction effect between group (PD vs. HC) and frequency, indicating decreased OAEs at low frequencies and increased OAEs at high frequencies in patients with PD. No significant differences were found between patients with PD and HCs regarding ES. In addition, no significant effect of medication status was found on auditory measurements in patients with PD. Conclusions Altered OAEs support the hypothesis of cochlear alterations in PD. No evidence was found for the involvement of the medial olivocochlear system. Altogether, OAEs may provide an objective early indicator of auditory alterations in PD and should complement subjective tonal audiometry when assessing and monitoring auditory function in PD.

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Cochlear Efferent Innervation Is Sparse in Humans and Decreases with Age

Cited by 38 publications

References 62 publications

Preventing presbycusis in mice with enhanced medial olivocochlear feedback

Preventing presbycusis in mice with enhanced medial olivocochlear feedback

Perceptual gating of a brainstem reflex facilitates speech understanding in human listeners

The Effect of Parkinson's Disease on Otoacoustic Emissions and Efferent Suppression of Transient Evoked Otoacoustic Emissions

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