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Effects of Kainic Acid-Induced Auditory Nerve Damage on Envelope-Following Responses in the Budgerigar (Melopsittacus undulatus)

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Abstract

Sensorineural hearing loss is a prevalent problem that adversely impacts quality of life by compromising interpersonal communication. While hair cell damage is readily detectable with the clinical audiogram, this traditional diagnostic tool appears inadequate to detect lost afferent connections between inner hair cells and auditory nerve (AN) fibers, known as cochlear synaptopathy. The envelope-following response (EFR) is a scalp-recorded response to amplitude modulation, a critical acoustic feature of speech. Because EFRs can have greater amplitude than wave I of the auditory brainstem response (ABR; i.e., the AN-generated component) in humans, the EFR may provide a more sensitive way to detect cochlear synaptopathy. We explored the effects of kainate- (kainic acid) induced excitotoxic AN injury on EFRs and ABRs in the budgerigar (Melopsittacus undulatus), a parakeet species used in studies of complex sound discrimination. Kainate reduced ABR wave I by 65–75 % across animals while leaving otoacoustic emissions unaffected or mildly enhanced, consistent with substantial and selective AN synaptic loss. Compared to wave I loss, EFRs showed similar or greater percent reduction following kainate for amplitude-modulation frequencies from 380 to 940 Hz and slightly less reduction from 80 to 120 Hz. In contrast, forebrain-generated middle latency responses showed no consistent change post-kainate, potentially due to elevated “central gain” in the time period following AN damage. EFR reduction in all modulation frequency ranges was highly correlated with wave I reduction, though within-animal effect sizes were greater for higher modulation frequencies. These results suggest that even low-frequency EFRs generated primarily by central auditory nuclei might provide a useful noninvasive tool for detecting synaptic injury clinically.

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Acknowledgments

Laurel Carney provided helpful comments on a previous version of the manuscript. This research was supported by a National Institute on Deafness and Other Communication Disorders grant (R00-DC013792 and R01-DC017519; P.I.: Henry) and a National Institutes of Health Ruth L. Kirschstein Individual Predoctoral National Research Service Award Fellowship (TL1 TR002000) administered by the University of Rochester Clinical and Translational Science Institute. The content of this publication is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. University of Rochester School of Medicine & Dentistry, Rochester, NY, USA

    John L. Wilson

  2. Department of Otolaryngology – Head & Neck Surgery, University of Rochester, Rochester, NY, USA

    John L. Wilson & Kenneth S. Henry

  3. Department of Neuroscience, University of Rochester, Rochester, NY, USA

    John L. Wilson, Kristina S. Abrams & Kenneth S. Henry

  4. Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA

    Kenneth S. Henry

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  1. John L. Wilson
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JLW and KSH designed the research, performed the experiments, analyzed the data, and wrote the manuscript. KSA performed the experiments.

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Correspondence to Kenneth S. Henry.

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Wilson, J.L., Abrams, K.S. & Henry, K.S. Effects of Kainic Acid-Induced Auditory Nerve Damage on Envelope-Following Responses in the Budgerigar (Melopsittacus undulatus). JARO 22, 33–49 (2021). https://doi.org/10.1007/s10162-020-00776-x

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