Abstract

The sound-evoked electrical compound potential known as auditory brainstem response (ABR) represents the firing of a heterogenous population of auditory neurons in response to sound stimuli, and is often used for clinical diagnosis based on wave amplitude and latency. However, recent ABR applications to detect human cochlear synaptopathy have led to inconsistent results, mainly due to the high variability of ABR wave-1 amplitude. Here, rather than focusing on the amplitude of ABR wave 1, we evaluated the use of ABR wave curvature to detect cochlear synaptic loss. We first compared four curvature quantification methods using simulated ABR waves, and identified that the cubic spline method using five data points produced the most accurate quantification. We next evaluated this quantification method with ABR data from an established mouse model with cochlear synaptopathy. The data clearly demonstrated that curvature measurement is more sensitive and consistent in identifying cochlear synaptic loss in mice compared to the amplitude and latency measurements. We further tested this curvature method in a different mouse model presenting with otitis media. The change in curvature profile due to middle ear infection in otitis media is different from the profile of mice with cochlear synaptopathy. Thus, our study suggests that curvature quantification can be used to address the current ABR variability issue, and may lead to additional applications in the clinic diagnosis of hearing disorders.

Highlights

  • In neurodegenerative diseases, synaptic loss often occurs before obvious functional changes

  • Instead of relying on amplitude measurements, we focused on curvature measurements, and identified that the cubic spline method calculated with five data points as the most accurate method for assessing changes of auditory brainstem response (ABR) wave 1

  • Using a well-established mouse model of cochlear synaptopathy, we demonstrated that these curvature measurements are more sensitive and consistent in identifying individual mice with cochlear synaptic loss compared to amplitude measurements

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Summary

Introduction

Synaptic loss often occurs before obvious functional changes. A similar early synaptic loss occurs in both the peripheral and central auditory systems (for recent reviews, Bharadwaj et al, 2019; Ibrahim and Llano, 2019; Kujawa and Liberman, 2019). The seminal discovery of cochlear synaptopathy was initially made in CBA/CaJ mice following moderate noise exposure (Kujawa and Liberman, 2009). They showed, using a precise quantification of synaptic loss by means of immunocytochemistry, the loss of up to half of the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs), despite full recovery of hearing thresholds as measured by auditory brainstem response (ABR). The DPOAE measurement is important because it eliminates possible confounding effects on the ABR wave I from damage to outer hair cells (OHCs)

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