Biology subjects

Dias, J. W.

Publications and source records attributed to Dias, J. W..

7 recordsLinked to original sources

bioRxiv2025

Age-related auditory nerve deficits propagate central gain throughout the auditory system: Associations with cortical microstructure and speech recognition

There is growing evidence that many perceptual difficulties associated with age-related hearing loss are not solely due to cochlear damage and are exacerbated by changes within the central nervous system. We examined electrophysiological (EEG) responses to clicks and diffusion kurtosis imaging (DKI) in 49 older (29 female) and 26 younger (20 female) adults to determine the extent to which auditory nerve (AN) deficits in older adults contributed to functional and structural changes throughout the auditory system. Older adults exhibited smaller AN responses, similar brainstem responses, and larger auditory cortex (AC) responses, demonstrating progressive "central gain". Audiometric thresholds were not predictive of EEG measures. Reduced AN function predicted deficits in cortical microstructure (lower AC fractional anisotropy, FA) in older adults, consistent with myelin degeneration. These lower FA values in the AC of older adults also predicted larger AC responses and more central gain. Older adults exhibited significantly lower AC FA and higher mean diffusivity (MD) than younger adults, and AC FA and MD were significant predictors of speech-in-noise (SIN) recognition in older adults. The results suggest that reduced afferent input in older adults not only results in functional changes throughout the auditory system consistent with progressive gain, but also contributes to deficits in AC structure beyond those explained by age alone, contributing to SIN deficits. Understanding the complex effects of age, reduced AN input, central gain, and AC structure on SIN recognition may provide potential therapeutic targets for intervention. SignificanceAge-related hearing loss is the most common sensory deficit with aging, but little is known about how the auditory cortex adapts to the chronic loss of afferent auditory input. We measured auditory nerve, brainstem, and cortical responses in younger and older adults. In older adults, deficits in afferent input predicted progressive hyperexcitability, or "central gain", at the brainstem and cortex. Smaller auditory nerve responses predicted poorer white matter structure in auditory cortex. Poorer white matter structure predicted smaller auditory cortex responses, more auditory cortical gain, and worse speech-in-noise recognition in older adults. This is the first study to show that reduced afferent input leads to both amplified cortical responses and reduced cortical integrity in older adults, contributing to speech-in-noise deficits.

neuroscience↗

bioRxiv2024

Effects of Age and Noise Exposure History on Auditory Nerve Response Amplitudes: A Systematic Review, Study, and Meta-Analysis

Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r=-0.407), but noise-exposure effects are weak (r=-0.152). We conclude that noise-exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.

neuroscience↗

bioRxiv2022

Sensory Tetanization to Induce LTP-Like Plasticity: A Review and Reassessment of the Approach

Great interest has been given to developing non-invasive approaches for studying cortical plasticity in humans. High frequency presentation of auditory and visual stimuli, or sensory tetanization, can induce long-term-potentiation-like (LTP-like) changes in cortical activity. However, contrasting effects across studies suggest that sensory tetanization may be unreliable. We review these contrasting effects, conduct our own study of auditory and visual tetanization, and perform meta-analyses to determine the average effect of sensory tetanization across studies. We measured auditory-evoked amplitude changes in a group of younger (18-29 years of age) and older (55-83 years of age) adults following tetanization to 1 kHz and 4 kHz tone bursts and following a slow-presentation control. We also measured visual-evoked amplitude changes following tetanization to horizontal and vertical sign gradients. Auditory and visual response amplitudes decreased following tetanization, consistent with some studies but contrasting with others finding amplitude increases (i.e., LTP-like changes). Older adults exhibited more modest auditory-evoked amplitude decreases, but visual-evoked amplitude decreases like those of younger adults. Changes in response amplitude were not specific to tetanized stimuli. Importantly, slow presentation of auditory tone-bursts produced response amplitude changes approximating those observed following tetanization in younger adults. Meta-analyses of visual and auditory tetanization studies found that the overall effect of sensory tetanization was not significant across studies or study sites. The results suggest that sensory tetanization may not produce reliable changes in cortical responses and more work is needed to determine the validity of sensory tetanization as a method for inducing human cortical plasticity in vivo.

neuroscience↗

bioRxiv2022

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

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.

neuroscience↗

bioRxiv2022

Cortical compensation for afferent loss in older adults: Associations with GABA and speech recognition in noise

Age-related deficits in auditory nerve (AN) function reduce afferent input to the auditory cortex. The extent to which the auditory cortex in older adults compensates for this loss of afferent input, also known as central gain, and the mechanisms underlying this compensation are not well understood. We took a neural systems approach to estimate central gain, measuring AN and cortical evoked responses within 50 older and 27 younger adults. Amplitudes were significantly smaller for older than for younger adults for AN responses but not for cortical responses. We used the relationship between AN and cortical response amplitudes in younger adults to predict cortical response amplitudes for older adults from their AN responses. Central gain in older adults was thus defined as the difference between their observed cortical responses and those predicted from the parameter estimates of younger adults. More central gain was associated with decreased cortical levels of GABA measured with 1H-MRS and poorer speech recognition in noise (SIN). Effects of central gain and GABA on SIN occur in addition to, and independent from, effects attributed to elevated hearing thresholds. Our results are consistent with animal models of central gain and suggest that reduced AN afferent input in some older adults may result in changes in cortical encoding and inhibitory neurotransmission, which contribute to reduced SIN. An advancement in our understanding of the changes that occur throughout the auditory system in response to the gradual loss of input with increasing age may provide potential therapeutic targets for intervention. SignificanceAge-related hearing loss is one of the most common chronic conditions of aging, yet little is known about how the cortex compensates for this loss of sensory input. We measured AN and cortical responses to the same stimulus in younger and older adults. In older adults we found an increase in cortical activity following concomitant declines in afferent input that are consistent with central gain. Increased central gain was associated with lower levels of cortical GABA, an inhibitory neurotransmitter, which predicted poorer speech recognition in noise. The results suggest that the cortex in older adults can compensate for attenuated sensory input by reducing inhibition to amplify the cortical response, but this amplification may lead to poorer speech recognition in noise.

neuroscience↗

bioRxiv2021

Two distinct types of nodes of Ranvier support auditory nerve function in the mouse cochlea

Glial cells of the auditory nerve regulate formation of the nodes of Ranvier that are needed for regeneration of action potentials and proper hearing function. Here we identify and describe the distinct features of two novel types of Ranvier nodes--the axonal node and the ganglion node--in the mouse auditory nerve that change across the lifespan, including during myelination and postnatal development, and degenerate during aging. Cellular, molecular, and structure-function correlation evaluations revealed that nodal types are critical for different aspects of auditory nerve function. Specifically, the length of the axonal node is associated with neural processing speed and neural synchrony, whereas ganglion node development is associated with amplitude growth of the action potential. Moreover, our data indicate that dysregulation of glial cells and associated degeneration of the ganglion node structure are an important and new mechanism of auditory nerve dysfunction in age-related hearing loss.

neuroscience↗

bioRxiv2017

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

Declines in auditory nerve (AN) function contribute to suprathreshold auditory processing and communication deficits in individuals with normal hearing, hearing loss, hyperacusis, and tinnitus. Procedures to characterize AN loss or dysfunction in humans are limited. We report several novel complementary metrics to characterize AN function noninvasively in humans using the compound action potential (CAP), a direct measure of summated AN activity. We examined how these metrics change with stimulus intensity, and interpreted these changes within a framework of known physiological properties of the basilar membrane and AN. Our results reveal how neural synchrony and the recruitment of AN fibers with later first-spike latencies likely contribute to the CAP, affect auditory processing, and differ with noise exposure history in younger adults despite normal pure-tone thresholds. Moving forward, these new metrics, when applied to patient populations, can provide a means to characterize cochlear synaptopathy and other deficits in AN function in humans.\n\nNew and noteworthy\n\nLoss or inactivity of auditory nerve (AN) fibers is thought to contribute to suprathreshold auditory processing deficits, but evidence-based methods to assess these effects are not available. We describe several novel metrics that may be used to quantify neural synchrony and characterize AN function.

neuroscience↗