Olivocochlear Changes Associated With Aging Predominantly Affect the Medial Olivocochlear System

Age-related hearing loss (ARHL) is a public health problem that has been associated with negative health outcomes ranging from increased frailty to an elevated risk of developing dementia. Significant gaps remain in our knowledge of the underlying central neural mechanisms, especially those related to the efferent auditory pathways. Thus, the aim of this study was to quantify and compare age-related alterations in the cholinergic olivocochlear efferent auditory neurons. We assessed, in young-adult and aged CBA mice, the number of cholinergic olivocochlear neurons, auditory brainstem response (ABR) thresholds in silence and in presence of background noise, and the expression of excitatory and inhibitory proteins in the ventral nucleus of the trapezoid body (VNTB) and in the lateral superior olive (LSO). In association with aging, we found a significant decrease in the number of medial olivocochlear (MOC) cholinergic neurons together with changes in the ratio of excitatory and inhibitory proteins in the VNTB. Furthermore, in old mice we identified a correlation between the number of MOC neurons and ABR thresholds in the presence of background noise. In contrast, the alterations observed in the lateral olivocochlear (LOC) system were less significant. The decrease in the number of LOC cells associated with aging was 2.7-fold lower than in MOC and in the absence of changes in the expression of excitatory and inhibitory proteins in the LSO. These differences suggest that aging alters the medial and lateral olivocochlear efferent pathways in a differential manner and that the changes observed may account for some of the symptoms seen in ARHL.

Cochlear nucleus small cells use olivocochlear collaterals to encode sounds in noise

Understanding speech, especially in noisy environments, is crucial to social interactions. Yet, as we age, speech processing can be disrupted by cochlear damage and the subsequent auditory nerve fiber degeneration. The most vulnerable-medium and high-threshold-auditory nerve fibers innervate various cell types in the cochlear nucleus, among which, the small cells are unique in receiving this input exclusively. Here, we characterize small cell firing characteristics, demonstrating superior temporal as well as intensity coding. We show that small-cell unique coding properties are facilitated by direct cholinergic input from the medial olivocochlear system. These results highlight the small cell-olivocochlear circuit as a key player in signal processing in noisy environments, which may be selectively degraded in aging or after noise insult.

Efferent feedback controls bilateral auditory spontaneous activity

In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation. The effects of peripheral firing patterns on spontaneous activity in the central auditory system are not well understood. Here, we describe wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the brainstem medial olivocochlear system. Knocking out α9/α10 nicotinic acetylcholine receptors, a requisite part of the efferent pathway, profoundly reduces bilateral correlations. Pharmacological and chemogenetic experiments confirm that the efferent system is necessary for normal bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, these results demonstrate how afferent and efferent pathways collectively shape spontaneous activity patterns and reveal the important role of efferents in coordinating bilateral spontaneous activity and the emergence of functional responses during the prehearing period.

Overexpression of Isl1 under the Pax2 Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus

The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse (Tg) expressing Isl1 under the Pax2 promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these Tg mice. In this study, we investigated how Isl1 overexpression affects sound processing by the neurons of the inferior colliculus (IC). We recorded extracellular neuronal activity and analyzed the responses of IC neurons to broadband noise, clicks, pure tones, two-tone stimulation and frequency-modulated sounds. We found that Tg animals showed a higher inhibition as displayed by two-tone stimulation; they exhibited a wider dynamic range, lower spontaneous firing rate, longer first spike latency and, in the processing of frequency modulated sounds, showed a prevalence of high-frequency inhibition. Functional changes were accompanied by a decreased number of calretinin and parvalbumin positive neurons, and an increased expression of vesicular GABA/glycine transporter and calbindin in the IC of Tg mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of Tg mice and demonstrate that major changes occur on the side of inhibition.

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

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.

Click evoked Middle Ear Muscle Reflex: Implications for Medial Olivocochlear System Assays

This study describes a time series-based method of middle ear muscle reflex (MEMR) detection using bilateral clicks, with implications for otoacoustic emission (OAE)-based medial olivocochlear reflex (MOCR) assays. Although current click-based methods can detect changes in the OAE evoking stimulus to monitor the MEMR, these methods do not discriminate between true MEMR-mediated vs. artifactual changes in the stimulus. We measured MEMR in 20 young clinically normal hearing individuals using a series of clicks presented at six levels (65 to 95 dB peak-to-peak SPL in 6 dB steps). Results were well-approximated by double-exponential functions. The change in ear canal pressure due to MEMR increased monotonically as a function of click level but non-monotonically with frequency. MEMR thresholds estimated using this method were lower than that obtained from a clinical tympanometer in ~94% of the participants. It is recommended that the OAE-evoking stimulus be monitored to determine the presence of MEMR across a wide band of frequencies in MOCR assays. A time series-based method, along with statistical tests, may provide additional confidence in detecting the MEMR. MEMR effects were smallest at 2 kHz which may provide avenues for minimizing the MEMR influence on the MOCR.

Electroacoustic and electrophysiological auditory assessment in aphasic individuals

ABSTRACT Purpose: to verify the functioning of the outer hair cells and the medial efferent olivocochlear system, and the integrity of the auditory pathways in the brainstem up to the auditory cortex, in aphasic individuals. Methods: the sample comprised 20 individuals - 10 without aphasia and 10 with it, aged from 21 to 58 years. The procedures used were the research of the otoacoustic emissions by a transient stimulus with and without noise, and the cognitive potential (tone-burst and speech stimuli). The findings were analyzed based on descriptive statistics. Results: the suppression effect was more present in individuals without aphasia when compared with the aphasic ones. In the cognitive potential, the mean latency values of P3 was within normality standards, with a higher latency in the individuals presented with aphasia for the tone-burst stimulus in both ears. A statistically significant difference of the P3-N2 amplitude was observed for the tone-burst stimulus, comparing the ears in both groups, and for speech stimulus only to the left ear in both groups. Conclusions: aphasic individuals did not present significant differences regarding suppression of the otoacoustic emissions. As for the cognitive potential, the aphasic individuals presented higher latency values when compared to those with no aphasia.