Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects
Cochlear synaptopathy is the loss of synapses between the inner hair cells and the auditory nerve despite survival of sensory hair cells. The findings of extensive cochlear synaptopathy in animals after moderate noise exposures challenged the long-held view that hair cells are the cochlear elements...
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| Format: | Article |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1104574/full |
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| author | Raymond A. Haggerty Kendall A. Hutson William J. Riggs Kevin D. Brown Kevin D. Brown Harold C. Pillsbury Harold C. Pillsbury Oliver F. Adunka Craig A. Buchman Douglas C. Fitzpatrick |
| author_facet | Raymond A. Haggerty Kendall A. Hutson William J. Riggs Kevin D. Brown Kevin D. Brown Harold C. Pillsbury Harold C. Pillsbury Oliver F. Adunka Craig A. Buchman Douglas C. Fitzpatrick |
| author_sort | Raymond A. Haggerty |
| collection | DOAJ |
| description | Cochlear synaptopathy is the loss of synapses between the inner hair cells and the auditory nerve despite survival of sensory hair cells. The findings of extensive cochlear synaptopathy in animals after moderate noise exposures challenged the long-held view that hair cells are the cochlear elements most sensitive to insults that lead to hearing loss. However, cochlear synaptopathy has been difficult to identify in humans. We applied novel algorithms to determine hair cell and neural contributions to electrocochleographic (ECochG) recordings from the round window of animal and human subjects. Gerbils with normal hearing provided training and test sets for a deep learning algorithm to detect the presence of neural responses to low frequency sounds, and an analytic model was used to quantify the proportion of neural and hair cell contributions to the ECochG response. The capacity to detect cochlear synaptopathy was validated in normal hearing and noise-exposed animals by using neurotoxins to reduce or eliminate the neural contributions. When the analytical methods were applied to human surgical subjects with access to the round window, the neural contribution resembled the partial cochlear synaptopathy present after neurotoxin application in animals. This result demonstrates the presence of viable hair cells not connected to auditory nerve fibers in human subjects with substantial hearing loss and indicates that efforts to regenerate nerve fibers may find a ready cochlear substrate for innervation and resumption of function. |
| first_indexed | 2024-03-13T00:51:20Z |
| format | Article |
| id | doaj.art-78ce488fd3e341f9a413b0988f936684 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-13T00:51:20Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-78ce488fd3e341f9a413b0988f9366842023-07-07T14:06:07ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-07-011410.3389/fneur.2023.11045741104574Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjectsRaymond A. Haggerty0Kendall A. Hutson1William J. Riggs2Kevin D. Brown3Kevin D. Brown4Harold C. Pillsbury5Harold C. Pillsbury6Oliver F. Adunka7Craig A. Buchman8Douglas C. Fitzpatrick9Department of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Otolaryngology, The Ohio State University, Columbus, OH, United StatesDepartment of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesUniversity of North Carolina School of Medicine, Chapel Hill, NC, United StatesDepartment of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesUniversity of North Carolina School of Medicine, Chapel Hill, NC, United StatesDepartment of Otolaryngology, The Ohio State University, Columbus, OH, United StatesDepartment of Otolaryngology, Washington University in St. Louis, St. Louis, MO, United StatesDepartment of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesCochlear synaptopathy is the loss of synapses between the inner hair cells and the auditory nerve despite survival of sensory hair cells. The findings of extensive cochlear synaptopathy in animals after moderate noise exposures challenged the long-held view that hair cells are the cochlear elements most sensitive to insults that lead to hearing loss. However, cochlear synaptopathy has been difficult to identify in humans. We applied novel algorithms to determine hair cell and neural contributions to electrocochleographic (ECochG) recordings from the round window of animal and human subjects. Gerbils with normal hearing provided training and test sets for a deep learning algorithm to detect the presence of neural responses to low frequency sounds, and an analytic model was used to quantify the proportion of neural and hair cell contributions to the ECochG response. The capacity to detect cochlear synaptopathy was validated in normal hearing and noise-exposed animals by using neurotoxins to reduce or eliminate the neural contributions. When the analytical methods were applied to human surgical subjects with access to the round window, the neural contribution resembled the partial cochlear synaptopathy present after neurotoxin application in animals. This result demonstrates the presence of viable hair cells not connected to auditory nerve fibers in human subjects with substantial hearing loss and indicates that efforts to regenerate nerve fibers may find a ready cochlear substrate for innervation and resumption of function.https://www.frontiersin.org/articles/10.3389/fneur.2023.1104574/fullelectrocochleographyauditory nervehair cellscochlear microphonicdeep learning |
| spellingShingle | Raymond A. Haggerty Kendall A. Hutson William J. Riggs Kevin D. Brown Kevin D. Brown Harold C. Pillsbury Harold C. Pillsbury Oliver F. Adunka Craig A. Buchman Douglas C. Fitzpatrick Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects Frontiers in Neurology electrocochleography auditory nerve hair cells cochlear microphonic deep learning |
| title | Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects |
| title_full | Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects |
| title_fullStr | Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects |
| title_full_unstemmed | Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects |
| title_short | Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects |
| title_sort | assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects |
| topic | electrocochleography auditory nerve hair cells cochlear microphonic deep learning |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1104574/full |
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