Predicting synapse counts in living humans by combining computational models with auditory physiology

Aging, noise exposure, and ototoxic medications lead to cochlear synapse loss in animal models. As cochlear function is highly conserved across mammalian species, synaptopathy likely occurs in humans as well. Synaptopathy is predicted to result in perceptual deficits including tinnitus, hyperacusis,...

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Bibliographic Details
Published in:The Journal of the Acoustical Society of America 2022-01, Vol.151 (1), p.561-576
Main Authors: Buran, Brad N., McMillan, Garnett P., Keshishzadeh, Sarineh, Verhulst, Sarah, Bramhall, Naomi F.
Format: Article
Language:English
Subjects:
Animals
Auditory Threshold
Cochlea
Computer Simulation
Evoked Potentials, Auditory, Brain Stem - physiology
Hearing Loss, Noise-Induced
Humans
Otoacoustic Emissions, Spontaneous - physiology
Psychological and Physiological Acoustics
Synapses
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Summary:Aging, noise exposure, and ototoxic medications lead to cochlear synapse loss in animal models. As cochlear function is highly conserved across mammalian species, synaptopathy likely occurs in humans as well. Synaptopathy is predicted to result in perceptual deficits including tinnitus, hyperacusis, and difficulty understanding speech-in-noise. The lack of a method for diagnosing synaptopathy in living humans hinders studies designed to determine if noise-induced synaptopathy occurs in humans, identify the perceptual consequences of synaptopathy, or test potential drug treatments. Several physiological measures are sensitive to synaptopathy in animal models including auditory brainstem response (ABR) wave I amplitude. However, it is unclear how to translate these measures to synaptopathy diagnosis in humans. This work demonstrates how a human computational model of the auditory periphery, which can predict ABR waveforms and distortion product otoacoustic emissions (DPOAEs), can be used to predict synaptic loss in individual human participants based on their measured DPOAE levels and ABR wave I amplitudes. Lower predicted synapse numbers were associated with advancing age, higher noise exposure history, increased likelihood of tinnitus, and poorer speech-in-noise perception. These findings demonstrate the utility of this modeling approach in predicting synapse counts from physiological data in individual human subjects.
ISSN:0001-4966
1520-8524
DOI:10.1121/10.0009238