Age-Related Primary Cochlear Neuronal Degeneration in Human Temporal Bones

Makary, Chadi A.; Shin, Jennifer J.; Kujawa, Sharon G.; Liberman, M. Charles; Merchant, Saumil N.

doi:10.1007/s10162-011-0283-2

Cited by 349 publications

(329 citation statements)

References 32 publications

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“…In contrast, previous animal studies showed that moderate noise exposure and early aging can produce synapse/ neuronal loss without changes to cochlear mechanics and with no hair cell loss-a completely different form of sensorineural hearing loss (Kujawa and Liberman, 2009;Makary et al, 2011;Sergeyenko et al, 2013). Here, we investigated whether perceptual differences in the general population of NH listeners who have no known hearing deficits are consistent with this mechanism of synaptopathy/neuropathy (Bharadwaj et al, 2014).…”

Section: Discussionmentioning

confidence: 68%

“…Aging also appears to reduce the effective auditory nerve fiber (ANF) population, initially through a loss of synapses with a subsequent degeneration of cell bodies (Makary et al, 2011;Sergeyenko et al, 2013). Furthermore, significant levels of deafferentation do not appear to affect detection thresholds (Schuknecht and Woellner, 1955;Lobarinas et al, 2013); however, in the healthy auditory system, convergence of nerve fibers is important for precise coding of both temporal finestructure and envelope cues in suprathreshold sounds (Joris et al, 1994;Lopez-Poveda and Barrios, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Individual Differences Reveal Correlates of Hidden Hearing Deficits

Bharadwaj¹,

Masud²,

Mehraei³

et al. 2015

J. Neurosci.

284

294

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Clinical audiometry has long focused on determining the detection thresholds for pure tones, which depend on intact cochlear mechanics and hair cell function. Yet many listeners with normal hearing thresholds complain of communication difficulties, and the causes for such problems are not well understood. Here, we explore whether normal-hearing listeners exhibit such suprathreshold deficits, affecting the fidelity with which subcortical areas encode the temporal structure of clearly audible sound. Using an array of measures, we evaluated a cohort of young adults with thresholds in the normal range to assess both cochlear mechanical function and temporal coding of suprathreshold sounds. Listeners differed widely in both electrophysiological and behavioral measures of temporal coding fidelity. These measures correlated significantly with each other. Conversely, these differences were unrelated to the modest variation in otoacoustic emissions, cochlear tuning, or the residual differences in hearing threshold present in our cohort. Electroencephalography revealed that listeners with poor subcortical encoding had poor cortical sensitivity to changes in interaural time differences, which are critical for localizing sound sources and analyzing complex scenes. These listeners also performed poorly when asked to direct selective attention to one of two competing speech streams, a task that mimics the challenges of many everyday listening environments. Together with previous animal and computational models, our results suggest that hidden hearing deficits, likely originating at the level of the cochlear nerve, are part of "normal hearing."

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Individual Differences Reveal Correlates of Hidden Hearing Deficits

Bharadwaj¹,

Masud²,

Mehraei³

et al. 2015

J. Neurosci.

284

294

View full text Add to dashboard Cite

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“…We determined whether ribbons were associated with glutamate receptors (GluA2) or afferent terminals (Na/K-ATPase). This analysis was aided by custom software that computed and displayed the x-y projection of the voxel space within 1 m of the center of each ribbon, as identified from the Amira analysis (Liberman et al, 2011). Juxtaposed ribbons and receptors or ribbons and terminals could then be viewed (and counted) within the generated array of thumbnails.…”

Section: Histologic Preparation and Assessmentmentioning

confidence: 99%

“…They require the biological motors in OHCs , which amplify sound-evoked cochlear vibration. They do not require IHCs or auditory nerve fibers (Takeno et al, 1994;Kujawa and Liberman, 2009). ABRs are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting IHCs (Buchwald and Huang, 1975).…”

Section: Cochlear Thresholds and Suprathreshold Response Growthmentioning

confidence: 99%

“…It has been known for decades that loss of auditory nerve fibers, the primary sensory neurons connecting the hair cells to the auditory brainstem, need not affect threshold sensitivity when the degeneration is diffusely distributed along the cochlear spiral (Schuknecht and Woellner, 1953). More recently, thresholds were shown to be insensitive to widespread loss of the inner hair cell (IHC) synapses of these neurons that can occur after noise exposures causing only temporary threshold elevations (Kujawa and Liberman, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Age-Related Cochlear Synaptopathy: An Early-Onset Contributor to Auditory Functional Decline

et al. 2013

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Aging listeners experience greater difficulty understanding speech in adverse listening conditions and exhibit degraded temporal resolution, even when audiometric thresholds are normal. When threshold evidence for peripheral involvement is lacking, central and cognitive factors are often cited as underlying performance declines. However, previous work has uncovered widespread loss of cochlear afferent synapses and progressive cochlear nerve degeneration in noise-exposed ears with recovered thresholds and no hair cell loss (Kujawa and Liberman 2009). Here, we characterize age-related cochlear synaptic and neural degeneration in CBA/CaJ mice never exposed to high-level noise. Cochlear hair cell and neuronal function was assessed via distortion product otoacoustic emissions and auditory brainstem responses, respectively. Immunostained cochlear whole mounts and plastic-embedded sections were studied by confocal and conventional light microscopy to quantify hair cells, cochlear neurons, and synaptic structures, i.e., presynaptic ribbons and postsynaptic glutamate receptors. Cochlear synaptic loss progresses from youth (4 weeks) to old age (144 weeks) and is seen throughout the cochlea long before age-related changes in thresholds or hair cell counts. Cochlear nerve loss parallels the synaptic loss, after a delay of several months. Key functional clues to the synaptopathy are available in the neural response; these can be accessed noninvasively, enhancing the possibilities for translation to human clinical characterization.

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