Temporal processing deficits due to noise-induced synaptopathy studied using envelope following responses

Description

Title
Temporal processing deficits due to noise-induced synaptopathy studied using envelope following responses

Authors:
Aravindakshan Parthasarathy - Post-Doc, Eaton-Peabody Labs, Mass. Eye and Ear; Department of Otolaryngology, Harvard Medical School (Role: First Author;Presenting Author)
Gerard Encina-Llamas - PhD Student, Technical University of Denmark (Role: Co-Author)
Barbara Shinn-Cunningham - Professor, Boston University (Role: Co-Author)
Sharon G. Kujawa - Associate Professor, Harvard Medical S chool and Massachussets Eye and Ear Infirmary (Role: Co-Author)

Introduction
Sound overexposure can result in a loss of synapses between inner hair cells (IHC) and the auditory nerve (AN) fibers. Although not manifested as changes in hearing thresholds, this synaptopathy may affect encoding of temporally complex stimuli, especially in conditions of background noise. Here, population envelope following responses (EFRs) were used to study suprathreshold temporal processing in a rodent model of synaptopathy. By also recreating these responses in a computational model of AN response, contributions of different spontaneous-rate (SR) fiber groups and the influence of off-frequency neurons to encoding suprathreshold sounds were explored.

Methods
EFRs were obtained from CBA/CaJ mice reared in quiet or after single exposure to a known synaptopathic noise that does not cause permanent hearing threshold elevations. EFR stimuli were tones, sinusoidally amplitude modulated (sAM) at 1024Hz that stimulated either synaptopathic or non-synaptopathic cochlear regions. First, tones were presented in quiet with modulation depths of 25% and 85% and sound levels from 20 to 80dBSPL. In the second experiment, fully modulated sAM tones were presented at a suprathreshold sound level, in varying levels of noise. ABR and DPOAE growth functions also were recorded, and immunostained cochlear whole-mounts were used to quantify hair cells and synapses. Results were compared to model-simulated EFRs with varying degrees of noise-induced synaptopathy. Contributions of off-channel, higher frequency neurons to the EFRs, as well as contributions of low, medium and high SR fibers were explored.

Results
Animals with noise-induced synaptopathy showed reduced EFR and ABR amplitudes, even though ABR and DPOAE thresholds and DPOAE amplitudes were recovered. These synaptopathic animals also showed a decreased dynamic range of noise masking in EFRs, relative to controls. The computational model recreated these responses. Off-frequency contributions of high-SR fibers dominated the modelled EFR amplitudes in quiet; however, these contributions were minimized at supra-threshold levels in the presence of noise masking.

Conclusions
Noise-induced synaptopathy causes deficits in temporal processing, as reflected in the EFR. Modelled results can account for the general trends obtained from the EFRs. Specifically, off-frequency contributions of high-SR fibers dominated the total modelled EFR in quiet. However, high-SR fiber contributions were reduced in broadband noise, consistent with a greater role for low- and medium-SR neurons in the temporal processing of sound signals in noise.

Funding provided by DoD W81XWH-15-1-0103 (SGK); CHeSS, Technical University of Denmark and ACN Erasmus Mundus scholarship (GEL).

Period	11 Feb 2017
Event title	40th MidWinter Meeting of the Association for Research in Otolaryngology
Event type	Conference
Location	Baltimore, United States, MarylandShow on map