Complementary metrics of human auditory nerve function derived from compound action potentials

Harris, Kelly C.; Vaden, Kenneth I.; McClaskey, Carolyn M.; Dias, James W.; Dubno, Judy R.

doi:10.1101/213157

Cited by 8 publications

(21 citation statements)

References 46 publications

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“…Whereas response amplitude is determined both by temporal jitter and by the response amplitudes within each trial, PLV reflects temporal jitter, independent from response amplitudes. Therefore, while PLV and response amplitudes both increase as stimulus level increases, as shown previously (Harris et al, 2018, 2021; McClaskey et al, 2020), examining these two measures together provides a means to dissociate synchrony from amplitude. PLV is calculated from a complex time-frequency transform, using the following equation, in which F k (f, t) is the spectral estimate of trial k at frequency f and time t : In this study, Hanning FFT tapers were applied to the continuous neural activity data, using the newtimef() function in EEGLAB.…”

Section: Methodssupporting

confidence: 59%

“…We fit hypothesis-driven LMER models to the AN and midbrain response measurements using the lme4 package for R (x64 v4.0.5). Amplitude and PLV at each frequently were modeled separately (e.g., Harris et al, 2018, 2021; McClaskey et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

“…Neural synchrony across trials, measured as the phase-locking value (PLV), has been demonstrated to predict speech recognition (Harris et al, 2021). In this study, we calculated the PLV of CAP and ABR responses to estimate neural synchrony (Harris et al, 2018, 2021, McClaskey et al, 2020). Models of amplitude and synchrony were then compared to determine whether age-related central gain improves synchrony in mice and human.…”

Section: Introductionmentioning

confidence: 99%

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Age-Related Central Gain with Degraded Neural Synchrony in the Auditory Brainstem of Mice and Humans

Rumschlag

McClaskey

Dias

et al. 2022

Preprint

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Aging is associated with auditory nerve (AN) functional deficits and decreased inhibition in the central auditory system, amplifying central responses in a process known as central gain. Although central gain enhances response amplitudes, central gain may not restore disrupted response timing. In this translational study, we measured responses from the AN and auditory midbrain in younger and older mice and humans. We hypothesized that older mice and humans exhibit central gain without an improvement in inter-trial synchrony in the midbrain. Our data demonstrated greater age-related deficits in AN response amplitudes than auditory midbrain response amplitudes, as shown by significant interactions between neural generator and age group, indicating central gain in auditory midbrain. However, synchrony decreases with age in both the AN and midbrain responses. These results reveal age-related central gain without concomitant improvements in synchrony, consistent with those predictions based on decreases in inhibition. Persistent decreases in synchrony may contribute to auditory processing deficits in older mice and humans.

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Section: Methodssupporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age-Related Central Gain with Degraded Neural Synchrony in the Auditory Brainstem of Mice and Humans

Rumschlag

McClaskey

Dias

et al. 2022

Preprint

Self Cite

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“…In other words, peak width and latency may be used to estimate the degeneration rate. This notion of peak width and latency being subject to the relative presence of different subpopulations (in our case healthy and degenerating neurons) has been previously described extensively by Harris et al (2018) in the context of contributions of two distinct populations of auditory nerve fibers (in their case the high-threshold low-spontaneous rate fibers and low-threshold high-spontaneous rate fibers) in the acoustically evoked CAP.…”

Section: Peak Width and Peak Area Represent Different Aspects Of Sgc ...mentioning

confidence: 76%

Changes in the Electrically Evoked Compound Action Potential over time After Implantation and Subsequent Deafening in Guinea Pigs

Ramekers

Benav

Klis

et al. 2022

JARO

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The electrically evoked compound action potential (eCAP) is a direct measure of the responsiveness of the auditory nerve to electrical stimulation from a cochlear implant (CI). CIs offer a unique opportunity to study the auditory nerve’s electrophysiological behavior in individual human subjects over time. In order to understand exactly how the eCAP relates to the condition of the auditory nerve, it is crucial to compare changes in the eCAP over time in a controlled model of deafness-induced auditory nerve degeneration. In the present study, 10 normal-hearing young adult guinea pigs were implanted and deafened 4 weeks later, so that the effect of deafening could be monitored within-subject over time. Following implantation, but before deafening, most examined eCAP characteristics significantly changed, suggesting increasing excitation efficacy (e.g., higher maximum amplitude, lower threshold, shorter latency). Conversely, inter-phase gap (IPG) effects on these measures – within-subject difference measures that have been shown to correlate well with auditory nerve survival – did not vary for most eCAP characteristics. After deafening, we observed an initial increase in excitability (steeper slope of the eCAP amplitude growth function (AGF), lower threshold, shorter latency and peak width) which typically returned to normal-hearing levels within a week, after which a slower process, probably reflecting spiral ganglion cell loss, took place over the remaining 6 weeks (e.g., decrease in maximum amplitude, AGF slope, peak area, and IPG effect for AGF slope; increase in IPG effect for latency). Our results suggest that gradual changes in peak width and latency reflect the rate of neural degeneration, while peak area, maximum amplitude, and AGF slope reflect neural population size, which may be valuable for clinical diagnostics.

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“…Suprathreshold estimates of AN peak response amplitudes and latency, and neural synchrony (Phase-locking value: PLV) were acquired. These suprathreshold measures of the ABR have been associated with speech recognition in noise (Harris et al, 2018, 2021).…”

Section: Methodsmentioning

confidence: 99%

Peripheral Auditory Nerve Impairment in a Mouse Model of Syndromic Autism

McChesney

Barth

Rumschlag

et al. 2022

Preprint

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Dysfunction of the peripheral auditory nerve (AN) contributes to dynamic changes throughout the central auditory system, resulting in abnormal auditory processing, including hypersensitivity. Altered sound sensitivity is frequently observed in autism spectrum disorder (ASD), suggesting that AN deficits and changes in auditory information processing may contribute to ASD-associated symptoms, including social communication deficits and hyperacusis. The MEF2C transcription factor is associated with risk for several neurodevelopmental disorders, and mutations or deletions of MEF2C produce a haploinsufficiency syndrome characterized by ASD, and language and cognitive deficits. A mouse model of this syndromic ASD (i.e., Mef2c+/- or Mef2c-Het) recapitulates many of the MEF2C Haploinsufficiency syndrome-linked behaviors including communication deficits. We show here that Mef2c-Het mice exhibit functional impairment of the peripheral AN and a modest reduction in hearing sensitivity. We find that MEF2C is expressed during development in multiple AN and cochlear cell types, and in Mef2c-Het mice, we observe multiple cellular and molecular alterations associated with the AN, including abnormal myelination, neuronal degeneration, neuronal mitochondria dysfunction, and increased macrophage activation and cochlear inflammation. These results reveal the importance of MEF2C function in inner ear development and function and the engagement of immune cells and other non-neuronal cells, which suggests that microglia/macrophages and other non-neuronal cells might contribute, directly or indirectly, to AN dysfunction and ASD-related phenotypes. Finally, our study establishes a comprehensive approach for characterizing AN function at the physiological, cellular, and molecular levels in mice, which can be applied to animal models with a wide range of human auditory processing impairments.

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Complementary metrics of human auditory nerve function derived from compound action potentials

Cited by 8 publications

References 46 publications

Age-Related Central Gain with Degraded Neural Synchrony in the Auditory Brainstem of Mice and Humans

Age-Related Central Gain with Degraded Neural Synchrony in the Auditory Brainstem of Mice and Humans

Changes in the Electrically Evoked Compound Action Potential over time After Implantation and Subsequent Deafening in Guinea Pigs

Peripheral Auditory Nerve Impairment in a Mouse Model of Syndromic Autism

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