Gap detection ability declines with central auditory neurodegeneration following age-related cochlear synaptopathy.

Age-related hearing impairment (ARHI) is commonly associated with decreased auditory temporal resolution caused by auditory neurodegeneration. Age-related deterioration in gap detection ability, resulting in poor temporal auditory processing, is often attributed to pathophysiological changes in both the peripheral and central auditory systems. This study aimed to investigate whether the gap detection ability declines in the early stages of ageing and to determine its usefulness in detecting peripheral and central auditory degeneration. The study used 1-month-old (1 M), 6-month-old (6 M) and 12-month-old (12 M) mice to examine changes in gap detection ability and associated auditory pathophysiology. Although hearing thresholds did not significantly differ between the groups, the amplitude of auditory brainstem response (ABR) wave I decreased significantly in an age-dependent manner, consistent with age-related cochlear synaptopathy. The relative ABR amplitude ratio of waves 2 and 5 to wave 1 was significantly increased in 12 M mice, indicating that the central auditory system had increased in relative neuroactivity. A significant increase in gap detection thresholds was observed in 12 M mice compared to 1 M mice. Although cochlear synaptopathy and central hyperactivity were positively correlated with gap detection thresholds, central hyperactivity strongly influenced gap detection ability. In the cochlear nucleus and auditory cortex, the inhibitory synaptic expression of GAD65 and the expression of parvalbumin were significantly decreased in 12 M mice, consistent with central hyperactivity. Evaluating gap detection performance may allow the identification of decreased auditory temporal resolution in the early stages of ARHI, which is strongly associated with auditory neurodegeneration.

Walking and balance in older adults with age-related hearing loss: A cross-sectional study of cases and matched controls.

BACKGROUND: Hearing loss (HL) is prevalent in older individuals. It is suggested that there is an association between age-related HL, walking and balance, leading to poorer function and increased risk of falls in older individuals. RESEARCH QUESTION: Is HL associated with physical performance, gait variability, and postural sway in older adults, and will additional dizziness moderate the effect of HL on balance? METHODS: In this cross-sectional study we examined 100 older individuals (age ≥70 years, 60 % females), divided in two groups, with or without age-related HL. Physical function and balance were evaluated by the Short Physical Performance Battery (SPPB), postural sway measured on a force platform (posturography), and balance in walking (gait variability) measured with a body-worn sensor. Multiple linear regression was used to examine the relationships between the variables, with physical function and balance as outcomes and HL as a dichotomous exposure (>30 dB). For all analyses, we further tested if associations were modified by self-reported dizziness. RESULTS: Multiple regression analysis with HL, age, sex, education, diabetes, and cardiovascular disease revealed a significant association between reduced SPPB and HL. Multiple linear regression analysis also showed that HL was associated with increased postural sway on firm surface with eyes open and closed after adjusting for age, sex, education, diabetes, and cardiovascular disease. There was significant association between HL and increased gait variability during dual task walking in all directions after adjusting for age, sex, education, diabetes, and cardiovascular disease. Further, we found that the association between HL and SPPB was significantly stronger in those with dizziness compared with those without dizziness. Dizziness also modified the association of HL with the other SPPB sub-scores but not for the other outcomes of postural sway or gait variability. SIGNIFICANCE: In this study, age-related HL was associated with worse physical performance as measured by SPPB, postural sway, and gait variability. This relationship illustrates the importance of assessing physical performance in people with HL to prevent risk of falls and disability.

Visual selective attention in individuals with age-related hearing loss.

Evidence from epidemiological studies suggests that hearing loss is associated with an accelerated decline in cognitive function, but the underlying pathophysiological mechanism remains poorly understood. Studies using auditory tasks have suggested that degraded auditory input increases the cognitive load for auditory perceptual processing and thereby reduces the resources available for other cognitive tasks. Attention-related networks are among the systems overrecruited to support degraded auditory perception, but it is unclear how they function when no excessive recruitment of cognitive resources for auditory processing is needed. Here, we implemented an EEG study using a nonauditory visual attentional selection task in 30 individuals with age-related hearing loss (ARHLs, 60-73 years) and compared them with aged (N = 30, 60-70 years) and young (N = 35, 22-29 years) normal-hearing controls. Compared with their normal-hearing peers, ARHLs demonstrated a significant amplitude reduction for the posterior contralateral N2 component, which is a well-validated index of the allocation of selective visual attention, despite the comparable behavioral performance. Furthermore, the amplitudes were observed to correlate significantly with hearing acuities (pure tone audiometry thresholds) and higher-order hearing abilities (speech-in-noise thresholds) in aged individuals. The target-elicited alpha lateralization, another mechanism of visuospatial attention, demonstrated in control groups was not observed in ARHLs. Although behavioral performance is comparable, the significant decrease in N2pc amplitude in ARHLs provides neurophysiologic evidence that may suggest a visual attentional deficit in ARHLs even without extra-recruitment of cognitive resources by auditory processing. It supports the hypothesis that constant degraded auditory input in ARHLs has an adverse impact on the function of cognitive control systems, which is a possible mechanism mediating the relationship between hearing loss and cognitive decline.

Voxelwise analysis of the central hearing pathway in senior dogs reveals changes associated with fractional lifespan.

Presbycusis, or age-related hearing loss, affects both elderly humans and dogs, significantly impairing their social interactions and cognition. In humans, presbycusis involves changes in peripheral and central auditory systems, with central changes potentially occurring independently. While peripheral presbycusis in dogs is well-documented, research on central changes remains limited. Diffusion tensor imaging (DTI) is a useful tool for detecting and quantifying cerebral white matter abnormalities. This study used DTI to explore the central auditory pathway of senior dogs, aiming to enhance our understanding of canine presbycusis. Dogs beyond 75% of their expected lifespan were recruited and screened with brainstem auditory evoked response testing to select dogs without severe peripheral hearing loss. Sixteen dogs meeting the criteria were scanned using a 3 T magnetic resonance scanner. Tract-based spatial statistics was used to analyze the central auditory pathways. A significant negative correlation between fractional lifespan and fractional anisotropy was found in the acoustic radiation, suggesting age-related white matter changes in the central auditory system. These changes, observed in dogs without severe peripheral hearing loss, may contribute to central presbycusis development.

A Step Toward Precision Audiology: Individual Differences and Characteristic Profiles From Auditory Perceptual and Cognitive Abilities.

Older adults with normal hearing or with age-related hearing loss face challenges when listening to speech in noisy environments. To better serve individuals with communication difficulties, precision diagnostics are needed to characterize individuals' auditory perceptual and cognitive abilities beyond pure tone thresholds. These abilities can be heterogenous across individuals within the same population. The goal of the present study is to consider the suprathreshold variability and develop characteristic profiles for older adults with normal hearing (ONH) and with hearing loss (OHL). Auditory perceptual and cognitive abilities were tested on ONH (n = 20) and OHL (n = 20) on an abbreviated test battery using portable automated rapid testing. Using cluster analyses, three main profiles were revealed for each group, showing differences in auditory perceptual and cognitive abilities despite similar audiometric thresholds. Analysis of variance showed that ONH profiles differed in spatial release from masking, speech-in-babble testing, cognition, tone-in-noise, and binaural temporal processing abilities. The OHL profiles differed in spatial release from masking, speech-in-babble testing, cognition, and tolerance to background noise performance. Correlation analyses showed significant relationships between auditory and cognitive abilities in both groups. This study showed that auditory perceptual and cognitive deficits can be present to varying degrees in the presence of audiometrically normal hearing and among listeners with similar degrees of hearing loss. The results of this study inform the need for taking individual differences into consideration and developing targeted intervention options beyond pure tone thresholds and speech testing.

Attenuation and distortion components of age-related hearing loss: Contributions to recognizing temporal-envelope filtered speech in modulated noise.

Older adults with hearing loss may experience difficulty recognizing speech in noise due to factors related to attenuation (e.g., reduced audibility and sensation levels, SLs) and distortion (e.g., reduced temporal fine structure, TFS, processing). Furthermore, speech recognition may improve when the amplitude modulation spectrum of the speech and masker are non-overlapping. The current study investigated this by filtering the amplitude modulation spectrum into different modulation rates for speech and speech-modulated noise. The modulation depth of the noise was manipulated to vary the SL of speech glimpses. Younger adults with normal hearing and older adults with normal or impaired hearing listened to natural speech or speech vocoded to degrade TFS cues. Control groups of younger adults were tested on all conditions with spectrally shaped speech and threshold matching noise, which reduced audibility to match that of the older hearing-impaired group. All groups benefitted from increased masker modulation depth and preservation of syllabic-rate speech modulations. Older adults with hearing loss had reduced speech recognition across all conditions. This was explained by factors related to attenuation, due to reduced SLs, and distortion, due to reduced TFS processing, which resulted in poorer auditory processing of speech cues during the dips of the masker.

Effects of neurofeedback training on the alpha activity in quantitative electroencephalography, cognitive function, and speech perception in elderly with presbycusis: a quasi-experimental study.

BACKGROUND: This study aimed to investigate the effects of neurofeedback training (NFT) on alpha activity in quantitative electroencephalography (QEEG), cognitive function, and speech perception in elderly with presbycusis. METHODS: This study was conducted from June 15 to November 30, 2020. The experimental group (n = 28) underwent NFT, while the control group (n = 31) was instructed to continue with their routine daily life. The NFT conducted for 40 min, two times a week, for a total of 16 sessions and was performed using Neuroharmony S and BrainHealth 2.7. The alpha activity was measured as alpha waves using QEEG. The cognitive function was measured using the Korean version of Mini-Mental Status Examination, digit span forward and backward (DSF and DSB). The speech perception was measured using the word and sentence recognition score (WRS and SRS) using an audiometer with the Korean Standard Monosyllabic Word Lists for Adults. RESULTS: The experimental group demonstrated improvement in the alpha wave of the left frontal lobe measured as alpha activity (t=-2.521, p = .018); MMSE-K (t=-3.467, p < .01), and DSF (t=-2.646, p < .05) measured as cognitive function; and WRS (t=-3.255, p = .003), and SRS (t=-2.851, p = .008) measured as speech perception compared to the control group. CONCLUSIONS: This study suggests that NFT could be considered an effective cognitive and auditory rehabilitation method based on brain and cognitive science for improving alpha activity, cognitive function, and speech perception.

Pathophysiological processes underlying hidden hearing loss revealed in Kcnt1/2 double knockout mice.

Presbycusis is a prevalent condition in older adults characterized by the progressive loss of hearing due to age-related changes in the cochlea, the auditory portion of the inner ear. Many adults also struggle with understanding speech in noise despite having normal auditory thresholds, a condition termed "hidden" hearing loss because it evades standard audiological assessments. Examination of animal models and postmortem human tissue suggests that hidden hearing loss is also associated with age-related changes in the cochlea and may, therefore, precede overt age-related hearing loss. Nevertheless, the pathological mechanisms underlying hidden hearing loss are not understood, which hinders the development of diagnostic biomarkers and effective treatments for age-related hearing loss. To fill these gaps in knowledge, we leveraged a combination of tools, including transcriptomic profiling and morphological and functional assessments, to identify these processes and examine the transition from hidden to overt hearing loss. As a novel approach, we took advantage of a recently characterized model of hidden hearing loss: Kcnt1/2 double knockout mice. Using this model, we find that even before observable morphological pathology, hidden hearing loss is associated with significant alteration in several processes, notably proteostasis, in the cochlear sensorineural structures, and increased susceptibility to overt hearing loss in response to noise exposure and aging. Our findings provide the first insight into the pathophysiology associated with the earliest and, therefore, most treatable stages of hearing loss and provide critical insight directing future investigation of pharmaceutical strategies to slow and possibly prevent overt age-related hearing loss.

The impact of age-related hearing loss on cognitive decline: The mediating role of brain age gap.

In recent years, the relationship between age-related hearing loss, cognitive decline, and the risk of dementia has garnered significant attention. The significant variability in brain health and aging among individuals of the same chronological age suggests that a measure assessing how one's brain ages may better explain hearing-cognition links. The main aim of this study was to investigate the mediating role of Brain Age Gap (BAG) in the association between hearing impairment and cognitive function. This research included 185 participants aged 20-79 years. BAG was estimated based on the difference between participant's brain age (estimated based on their structural T1-weighted MRI scans) and chronological age. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test while hearing ability was measured using pure-tone thresholds (PTT) and words-in-noise (WIN) perception. Mediation analyses were used to examine the mediating role of BAG in the relationship between age-related hearing loss as well as difficulties in WIN perception and cognition. Participants with poorer hearing sensitivity and WIN perception showed lower MoCA scores, but this was an indirect effect. Participants with poorer performance on PTT and WIN tests had larger BAG (accelerated brain aging), and this was associated with poorer performance on the MoCA test. Mediation analyses showed that BAG partially mediated the relationship between age-related hearing loss and cognitive decline. This study enhances our understanding of the interplay among hearing loss, cognition, and BAG, emphasizing the potential value of incorporating brain age assessments in clinical evaluations to gain insights beyond chronological age, thus advancing strategies for preserving cognitive health in aging populations.

miR-130b-3p involved in the pathogenesis of age-related hearing loss via targeting PPARγ and autophagy.

The study focuses on the underlying regulatory mechanism of age-related hearing loss (ARHL), which results from autophagy dysregulation mediated by miR-130b-3p targeting PPARγ. We constructed miR-130b-3p knockout (antagomir) and PPARγ over-expression (OE-PPARγ) mice model by injecting mmu-miR-130b-3p antagomir and HBAAV2/Anc80-m-Pparg-T2A-mCHerry into the right ear' round window of each mouse, respectively. In vitro, we introduced oxidative stress within HEI-OC1 cells by H2O2 and exogenously changed the miR-130b-3p and PPARγ levels. MiRNA level was detected by RT-qPCR, proteins by western blotting and immunohistochemistry. Morphology of autophagosomes was observed by electron microscopy. In vivo, the cochlea of aged mice showed higher miR-130b-3p expression and lower PPARγ expression, while exogenous inhibition of miR-130b-3p up-regulated PPARγ expression. Autophagy-related biomarkers expression (ATG5, Beclin-1 and LC3B II/I) decreased in aged mice, which reversely increased after the inhibition of miR-130b-3p. The elevation of PPARγ demonstrated similar effects. Contrarily, exogenous overexpression of miR-130b-3p resulted in the decrease of ATG5, Beclin-1 and LC3B II/I. We created oxidative stress within HEI-OC1 by H2O2, subsequently observed the formation of autophagosomes under electron microscope, so as the elevated cell apoptosis rate and weakened cell viability. MiR-130b-3p/PPARγ contributed to the premature senescence of these H2O2-induced HEI-OC1 cells. MiR-130b-3p regulated HEI-OC1 cell growth by targeting PPARγ, thus leading to ARHL.

Aberrant auditory metabolite levels and topological properties are associated with cognitive decline in presbycusis patients.

Presbycusis has been reported as related to cognitive decline, but its underlying neurophysiological mechanism is still unclear. This study aimed to investigate the relationship between metabolite levels, cognitive function, and node characteristics in presbycusis based on graph theory methods. Eighty-four elderly individuals with presbycusis and 63 age-matched normal hearing controls underwent magnetic resonance spectroscopy, functional magnetic resonance imaging scans, audiological assessment, and cognitive assessment. Compared with the normal hearing group, presbycusis patients exhibited reduced gamma-aminobutyric acid and glutamate levels in the auditory region, increased nodal characteristics in the temporal lobe and precuneus, as well as decreased nodal characteristics in the superior occipital gyrus and medial orbital. The right gamma-aminobutyric acid levels were negatively correlated with the degree centrality in the right precuneus and the executive function. Degree centrality in the right precuneus exhibited significant correlations with information processing speed and executive function, while degree centrality in the left medial orbital demonstrated a negative association with speech recognition ability. The degree centrality and node efficiency in the superior occipital gyrus exhibited a negative association with hearing loss and speech recognition ability, respectively. These observed changes indicate alterations in metabolite levels and reorganization patterns at the brain network level after auditory deprivation.

Hearing loss-related altered neuronal activity in the inferior colliculus.

Hearing loss is well known to cause plastic changes in the central auditory system and pathological changes such as tinnitus and hyperacusis. Impairment of inner ear functions is the main cause of hearing loss. In aged individuals, not only inner ear dysfunction but also senescence of the central nervous system is the cause of malfunction of the auditory system. In most cases of hearing loss, the activity of the auditory nerve is reduced, but that of the successive auditory centers is increased in a compensatory way. It has been reported that activity changes occur in the inferior colliculus (IC), a critical nexus of the auditory pathway. The IC integrates the inputs from the brainstem and drives the higher auditory centers. Since abnormal activity in the IC is likely to affect auditory perception, it is crucial to elucidate the neuronal mechanism to induce the activity changes of IC neurons with hearing loss. This review outlines recent findings on hearing-loss-induced plastic changes in the IC and brainstem auditory neuronal circuits and discusses what neuronal mechanisms underlie hearing-loss-induced changes in the activity of IC neurons. Considering the different causes of hearing loss, we discuss age-related hearing loss separately from other forms of hearing loss (non-age-related hearing loss). In general, the main plastic change of IC neurons caused by both age-related and non-age-related hearing loss is increased central gain. However, plastic changes in the IC caused by age-related hearing loss seem to be more complex than those caused by non-age-related hearing loss.

The Stria Vascularis: Renewed Attention on a Key Player in Age-Related Hearing Loss.

Age-related hearing loss (HL), or presbycusis, is a complex and heterogeneous condition, affecting a significant portion of older adults and involving various interacting mechanisms. Metabolic presbycusis, a type of age-related HL, is characterized by the dysfunction of the stria vascularis, which is crucial for maintaining the endocochlear potential necessary for hearing. Although attention on metabolic presbycusis has waned in recent years, research continues to identify strial pathology as a key factor in age-related HL. This narrative review integrates past and recent research, bridging findings from animal models and human studies, to examine the contributions of the stria vascularis to age-related HL. It provides a brief overview of the structure and function of the stria vascularis and then examines mechanisms contributing to age-related strial dysfunction, including altered ion transport, changes in pigmentation, inflammatory responses, and vascular atrophy. Importantly, this review outlines the contribution of metabolic mechanisms to age-related HL, highlighting areas for future research. It emphasizes the complex interdependence of metabolic and sensorineural mechanisms in the pathology of age-related HL and highlights the importance of animal models in understanding the underlying mechanisms. The comprehensive and mechanistic investigation of all factors contributing to age-related HL, including cochlear metabolic dysfunction, remains crucial to identifying the underlying mechanisms and developing personalized, protective, and restorative treatments.

Characteristics of spatial protein expression in the mouse cochlear sensory epithelia: Implications for age-related hearing loss.

Hair cells in the cochlear sensory epithelia serve as mechanosensory receptors, converting sound into neuronal signals. The basal sensory epithelia are responsible for transducing high-frequency sounds, while the apex handles low-frequency sounds. Age-related hearing loss predominantly affects hearing at high frequencies and is indicative of damage to the basal sensory epithelia. However, the precise mechanism underlying this site-selective injury remains unclear. In this study, we employed a microscale proteomics approach to examine and compare protein expression in different regions of the cochlear sensory epithelia (upper half and lower half) in 1.5-month-old (normal hearing) and 6-month-old (severe high-frequency hearing loss without hair cell loss) C57BL/6J mice. A total of 2,386 proteins were detected, and no significant differences in protein expression were detected in the upper half of the cochlear sensory epithelia between the two age groups. The expression of 20 proteins in the lower half of the cochlear sensory epithelia significantly differed between the two age groups (e.g., MATN1, MATN4, and AQP1). Moreover, there were 311 and 226 differentially expressed proteins between the upper and lower halves of the cochlear sensory epithelia in 1.5-month-old and 6-month-old mice, respectively. The expression levels of selected proteins were validated by Western blotting. These findings suggest that the spatial differences in protein expression within the cochlear sensory epithelia may play a role in determining the susceptibility of cells at different sites of the cochlea to age-related damage.

Electrocochleographic frequency-following responses as a potential marker of age-related cochlear neural degeneration.

Auditory nerve (AN) fibers that innervate inner hair cells in the cochlea degenerate with advancing age. It has been proposed that age-related reductions in brainstem frequency-following responses (FFR) to the carrier of low-frequency, high-intensity pure tones may partially reflect this neural loss in the cochlea (Märcher-Rørsted et al., 2022). If the loss of AN fibers is the primary factor contributing to age-related changes in the brainstem FFR, then the FFR could serve as an indicator of cochlear neural degeneration. In this study, we employed electrocochleography (ECochG) to investigate the effects of age on frequency-following neurophonic potentials, i.e., neural responses phase-locked to the carrier frequency of the tone stimulus. We compared these findings to the brainstem-generated FFRs obtained simultaneously using the same stimulation. We conducted recordings in young and older individuals with normal hearing. Responses to pure tones (250 ms, 516 and 1086 Hz, 85 dB SPL) and clicks were recorded using both ECochG at the tympanic membrane and traditional scalp electroencephalographic (EEG) recordings of the FFR. Distortion product otoacoustic emissions (DPOAE) were also collected. In the ECochG recordings, sustained AN neurophonic (ANN) responses to tonal stimulation, as well as the click-evoked compound action potential (CAP) of the AN, were significantly reduced in the older listeners compared to young controls, despite normal audiometric thresholds. In the EEG recordings, brainstem FFRs to the same tone stimulation were also diminished in the older participants. Unlike the reduced AN CAP response, the transient-evoked wave-V remained unaffected. These findings could indicate that a decreased number of AN fibers contributes to the response in the older participants. The results suggest that the scalp-recorded FFR, as opposed to the clinical standard wave-V of the auditory brainstem response, may serve as a more reliable indicator of age-related cochlear neural degeneration.

L-Ergothioneine slows the progression of age-related hearing loss in CBA/CaJ mice.

The naturally occurring amino acid, l-ergothioneine (EGT), has immense potential as a therapeutic, having shown promise in the treatment of other disease models, including neurological disorders. EGT is naturally uptaken into cells via its specific receptor, OCTN1, to be utilized by cells as an antioxidant and anti-inflammatory. In our current study, EGT was administered over a period of 6 months to 25-26-month-old CBA/CaJ mice as a possible treatment for age-related hearing loss (ARHL), since presbycusis has been linked to higher levels of cochlear oxidative stress, apoptosis, and chronic inflammation. Results from the current study indicate that EGT can prevent aging declines of some key features of ARHL. However, we found a distinct sex difference for the response to the treatments, for hearing - Auditory Brainstem Responses (ABRs) and Distortion Product Otoacoustic Emissions (DPOAEs). Males exhibited lower threshold declines in both low dose (LD) and high dose (HD) test groups throughout the testing period and did not display some of the characteristic aging declines in hearing seen in Control animals. In contrast, female mice did not show any therapeutic effects with either treatment dose. Further confirming this sex difference, EGT levels in whole blood sampling throughout the testing period showed greater uptake of EGT in males compared to females. Additionally, RT-PCR results from three tissue types of the inner ear confirmed EGT activity in the cochlea in both males and females. Males and females exhibited significant differences in biomarkers related to apoptosis (Cas-3), inflammation (TNF-a), oxidative stress (SOD2), and mitochondrial health (PGC1a).These changes were more prominent in males as compared to females, especially in stria vascularis tissue. Taken together, these findings suggest that EGT has the potential to be a naturally derived therapeutic for slowing down the progression of ARHL, and possibly other neurodegenerative diseases. EGT, while effective in the treatment of some features of presbycusis in aging males, could also be modified into a general prophylaxis for other age-related disorders where treatment protocols would include eating a larger proportion of EGT-rich foods or supplements. Lastly, the sex difference discovered here, needs further investigation to see if therapeutic conditions can be developed where aging females show better responsiveness to EGT.

Surface electrical stimulation of the auditory cortex preserves efferent medial olivocochlear neurons and reduces cochlear traits of age-related hearing loss.

The auditory cortex is the source of descending connections providing contextual feedback for auditory signal processing at almost all levels of the lemniscal auditory pathway. Such feedback is essential for cognitive processing. It is likely that corticofugal pathways are degraded with aging, becoming important players in age-related hearing loss and, by extension, in cognitive decline. We are testing the hypothesis that surface, epidural stimulation of the auditory cortex during aging may regulate the activity of corticofugal pathways, resulting in modulation of central and peripheral traits of auditory aging. Increased auditory thresholds during ongoing age-related hearing loss in the rat are attenuated after two weeks of epidural stimulation with direct current applied to the surface of the auditory cortex for two weeks in alternate days (Fernández del Campo et al., 2024). Here we report that the same cortical electrical stimulation protocol induces structural and cytochemical changes in the aging cochlea and auditory brainstem, which may underlie recovery of age-degraded auditory sensitivity. Specifically, we found that in 18 month-old rats after two weeks of cortical electrical stimulation there is, relative to age-matched non-stimulated rats: a) a larger number of choline acetyltransferase immunoreactive neuronal cell body profiles in the ventral nucleus of the trapezoid body, originating the medial olivocochlear system.; b) a reduction of age-related dystrophic changes in the stria vascularis; c) diminished immunoreactivity for the pro-inflammatory cytokine TNFα in the stria vascularis and spiral ligament. d) diminished immunoreactivity for Iba1 and changes in the morphology of Iba1 immunoreactive cells in the lateral wall, suggesting reduced activation of macrophage/microglia; d) Increased immunoreactivity levels for calretinin in spiral ganglion neurons, suggesting excitability modulation by corticofugal stimulation. Altogether, these findings support that non-invasive neuromodulation of the auditory cortex during aging preserves the cochlear efferent system and ameliorates cochlear aging traits, including stria vascularis dystrophy, dysregulated inflammation and altered excitability in primary auditory neurons.

Central Auditory Changes Associated with Age-related Hearing Loss.

Objective. This study aimed to investigate age-related changes in cortical auditory evoked potentials (CAEPs) while considering three crucial factors: aging, high-frequency hearing loss and sensation level of the CAEP stimulus. Method. The electrophysiological and audiometric data of 71 elderly participants were analyzed using multiple regression analysis to investigate the association of CAEPs with the factors of aging, high-frequency hearing loss and sensation level of the CAEP test stimulus. Results. Aging was significantly associated with prolonged N1 and P2 latencies and reduced P2 amplitude. Elevated thresholds related to the sensation level of the CAEP stimulus were significantly associated with increased N1 and P2 amplitudes and decreased N1 latency. A significant relationship was detected between high-frequency hearing thresholds and the shortening of P2 latencies and the reduction of P2 amplitudes. Conclusion. The results of this study highlight the complex interplay of aging, high-frequency hearing loss and the sensation level of the CAEP stimulus on CAEP components in elderly people. These factors should be considered in future research using CAEPs to enhance overall understanding of auditory processing in the aging population.

Relationship Between Serum Brain-Derived Neurotrophic Factor and Neurotrophin-3 Levels and Hearing Thresholds in Patients With Age-Related Hearing Loss.

BACKGROUND: Age-related hearing loss (ARHL) is a general term used to describe the sensorineural type of hearing loss occurring in both ears in older adults. Neurotrophins are the most promising candidates for supporting the auditory nerve by increasing neuronal survival. This study aimed to help elucidate the pathophysiology of ARHL by determining whether any relationship exists between brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) levels in serum samples from patients diagnosed with ARHL. MATERIALS AND METHOD: Seventy-seven individuals, a study group of 41 patients diagnosed with ARHL, and a control group of 36 participants without hearing loss were evaluated. Serum samples were collected and used to measure serum BDNF and NT-3 levels with the new Nepenthe enzyme-linked immunosorbent assay method. RESULTS: Median pure-tone average results in the 2000, 4000, and 6000 Hz ranges were 52.5 (44.3-67.3) dB HL in the ARHL group and 13.5 (11.1-17.1) dB HL in the control group. The difference was statistically significant (p = .001). Although NT-3 and BDNF levels were both lower in ARHL patients than in participants without hearing loss, only the BDNF levels were significantly (p = .002) lower. Mean left and right ear word recognition scores were also lower in ARHL patients than in control groups. The ARHL group was further divided into two subgroups based on word recognition scores to evaluate significant differences in BDNF and NT-3 levels. No statistically significant difference was observed in BDNF and NT-3 levels between these subgroups. However, there was a significant difference in word recognition scores. CONCLUSIONS: Low BDNF levels in the ARHL group suggest that BDNF may play a role in the pathogenesis of ARHL. Patients with low (ARHL1) and high (ARHL2) word recognition scores were compared for the first time in the literature in terms of BDNF and NT-3 levels. However, the results were not statistically significant. This article is a preliminary study and was written to provide guidance for our next comprehensive project.

Temporal acuity is preserved in the auditory midbrain of aged mice.

Impaired temporal resolution of the central auditory system has long been suggested to contribute to speech understanding deficits in the elderly. However, it has been difficult to differentiate between direct age-related central deficits and indirect effects of confounding peripheral age-related hearing loss on temporal resolution. To differentiate this, we measured temporal acuity in the inferior colliculus (IC) of aged CBA/J and C57BL/6 mice, as a model of aging with and without concomitant hearing loss. We used two common measures of auditory temporal processing: gap detection as a measure of temporal fine structure and amplitude-modulated noise as a measure of envelope sensitivity. Importantly, auditory temporal acuity remained precise in the IC of old CBA/J mice when no or only minimal age-related hearing loss was present. In contrast, temporal acuity was only indirectly reduced by the presence of age-related hearing loss in aged C57BL/6 mice, not by affecting the brainstem precision, but by affecting the signal-to-noise ratio of the neuronal activity in the IC. This demonstrates that indirect effects of age-related peripheral hearing loss likely remain an important factor for temporal processing in aging in comparison to 'pure' central auditory decline itself. It also draws attention to the issue that the threshold difference between 'nearly normal' or 'clinically normal' hearing aging subjects in comparison to normal hearing young subjects still can have indirect effects on central auditory neural representations of temporal processing.