Age-related hearing loss is a complex phenomenon. The earliest-onset degenerative event is the gradual loss of neural connections between the cochlea and auditory brainstem. To probe for perceptual deficits that might arise from this loss, cochlear synaptopathy was induced pharmacologically in young-adult gerbils, which were then tested in a challenging listening task for the perception of temporal fine structure. Treated gerbils behaved no differently than normal-hearing, young-adult animals. In contrast, old gerbils, which typically express many cochlear and central-neural pathologies, showed impaired perception. To probe for the underlying mechanisms, single-unit responses were obtained from the auditory nerve to the same test stimuli. Responses from old gerbils showed no impairment in temporal locking to the stimulus fine structure. However, responses were significantly more driven by slower temporal fluctuations of the stimulus envelope, suggesting that the central auditory system may be unable to extract the relevant information for discrimination from such altered inputs.

Exposure to loud sounds can lead to hearing impairments. Speech comprehension, especially in the presence of background sounds, allegedly declines as a consequence of noise-induced hearing loss. However, the connection between noise overexposure and deteriorated speech-in-noise perception is not clear yet and potential underlying mechanisms are still under debate. This study investigates speech-in-noise discrimination in young-adult Mongolian gerbils before and after an acoustic trauma to reveal possible noise-induced changes in the perception of speech sounds and to examine the commonly suggested link between noise exposure and speech-in-noise perception difficulties. Nine young-adult gerbils were trained to discriminate a deviant consonant-vowel-consonant combination (CVC) or vowel-consonant-vowel combination (VCV) in a sequence of CVC or VCV standards, respectively. The logatomes were spoken by different speakers and masked by a steady-state speech-shaped noise. After the gerbils completed the behavioral baseline experiments, they underwent an acoustic trauma and collected data for the second time in the behavioral experiments. Applying multidimensional scaling, response latencies were used to generate perceptual maps reflecting the gerbils' internal representations of the sounds pre- and post-trauma. To evaluate how the discrimination of vowels and consonants was altered after the acoustic trauma, changes in response latencies between phoneme pairs were investigated with regard to their articulatory features. Auditory brainstem responses were measured to assess peripheral auditory function. We found that the perceptual maps of vowels and consonants were very similar before and after noise exposure. Interestingly, the gerbils' overall vowel discrimination ability was improved after the acoustic trauma, even though the gerbils suffered from noise-induced hearing loss. In contrast to the improvements in vowel discrimination, there were only minor changes in the gerbils' ability to discriminate consonants. Moreover, the noise exposure showed a differential influence on the response latencies for vowel and consonant discriminations depending on the articulatory features of the specific phonemes. ### Competing Interest Statement The authors have declared no competing interest.

Presbycusis, or age-related hearing loss, is a prevalent condition characterized by progressive auditory decline, significantly impacting quality of life in older adults. While sensorineural damage has been widely studied, degeneration of the stria vascularis (SV) remains underexplored despite its essential role in cochlear ion homeostasis. The SV is organized into three cellular layers-marginal, intermediate, and basal cells-each with distinct functions critical for maintaining the endocochlear potential. Using the quiet-aged Mongolian gerbil-a well-established model of metabolic presbycusis-we systematically mapped the structural and cellular degeneration of the SV and linked these changes to cochlear function. We assessed cochlear function using auditory brainstem response (ABR) measurements and quantified age-related atrophy of the strial cell layers using immunofluorescence, confocal microscopy, and 3D reconstruction. We identified a striking, region-specific pattern of degeneration, with the greatest atrophy occurring in ATP1A1-expressing marginal cells, followed by KCNJ10-expressing intermediate cells, and comparatively little atrophy in CLDN11-expressing basal cells. Notably, atrophy was most pronounced in the cochlear apex and base, regions critical for low- and high-frequency hearing. We further established a significant correlation between the decline in cochlear function and the extent of atrophy of the individual strial cell layers, especially in the cochlear base. By moving beyond traditional cross-sectional assessments of age-related degeneration of the SV, this work provides a more nuanced understanding of how strial pathology contributes to age-related decline in cochlear function and may inform therapeutic interventions targeting strial function to mitigate age-related hearing loss even when sensorineural function is compromised.

Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.

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.

In mammalian hearing, type-I afferent auditory nerve fibers comprise the basis of the afferent auditory pathway. They are connected to inner hair cells of the cochlea via specialized ribbon synapses. Auditory nerve fibers of different physiological types differ subtly in their synaptic location and morphology. Low-spontaneous-rate auditory nerve fibers typically connect on the modiolar side of the inner hair cell, while high-spontaneous-rate fibers are typically found on the pillar side. In aging and noise-damaged ears, this fine-tuned balance between auditory nerve fiber populations can be disrupted and the functional consequences are currently unclear. Here, using immunofluorescent labeling of presynaptic ribbons and postsynaptic glutamate receptor patches, we investigated changes in synaptic morphology at three different tonotopic locations along the cochlea of aging gerbils compared to those of young adults. Quiet-aged gerbils showed about 20% loss of afferent ribbon synapses. While the loss was random at apical, low-frequency cochlear locations, at the basal, high-frequency location it almost exclusively affected the modiolar-located synapses. The subtle differences in volumes of pre- and postsynaptic elements located on the inner hair cell’s modiolar versus pillar side were unaffected by age. This is consistent with known physiology and suggests a predominant, age-related loss in the low-spontaneous-rate auditory nerve population in the cochlear base, but not the apex.

Masking can reduce the efficiency of communication and prey and predator detection. Most underwater sounds fluctuate in amplitude, which may influence the amount of masking experienced by marine mammals. The hearing thresholds of two harbor seals for tonal sweeps (centered at 4 and 32 kHz) masked by sinusoidal amplitude modulated (SAM) Gaussian one-third octave noise bands centered around the narrow-band test sweep frequencies, were studied with a psychoacoustic technique. Masking was assessed in relation to signal duration, (500, 1000, and 2000 ms) and masker level, at eight amplitude modulation rates (1-90 Hz). Masking release (MR) due to SAM compared thresholds in modulated and unmodulated maskers. Unmodulated maskers resulted in critical ratios of 21 dB at 4 kHz and 31 dB at 32 kHz. Masked thresholds were similarly affected by SAM rate with the lowest thresholds and the largest MR being observed for SAM rates of 1 and 2 Hz at higher masker levels. MR was higher for 32-kHz maskers than for 4-kHz maskers. Increasing signal duration from 500 ms to 2000 ms had minimal effect on MR. The results are discussed with respect to MR resulting from envelope variation and the impact of noise in the environment on target signal detection.

Age-related hearing loss is of increasing concern in our ageing society. However, a causal understanding of the manifold degenerative processes in the cochlea and auditory brain, and their relation to specific hearing problems, is still in its infancy. Gerbils that are trained to perform auditory tasks show very similar auditory perception to humans, including in tests with speech-like signals. This offers a unique opportunity to experimentally probe age-related changes in perception and the underlying neural pathologies.

IntroductionUnderstanding speech in a noisy environment, as opposed to speech in quiet, becomes increasingly more difficult with increasing age. Using the quiet-aged gerbil, we studied the effects of aging on speech-in-noise processing. Specifically, behavioral vowel discrimination and the encoding of these vowels by single auditory-nerve fibers were compared, to elucidate some of the underlying mechanisms of age-related speech-in-noise perception deficits.MethodsYoung-adult and quiet-aged Mongolian gerbils, of either sex, were trained to discriminate a deviant naturally-spoken vowel in a sequence of vowel standards against a speech-like background noise. In addition, we recorded responses from single auditory-nerve fibers of young-adult and quiet-aged gerbils while presenting the same speech stimuli.ResultsBehavioral vowel discrimination was not significantly affected by aging. For both young-adult and quiet-aged gerbils, the behavioral discrimination between /eː/ and /iː/ was more difficult to make than /eː/ vs. /aː/ or /iː/ vs. /aː/, as evidenced by longer response times and lower d’ values. In young-adults, spike timing-based vowel discrimination agreed with the behavioral vowel discrimination, while in quiet-aged gerbils it did not. Paradoxically, discrimination between vowels based on temporal responses was enhanced in aged gerbils for all vowel comparisons. Representation schemes, based on the spectrum of the inter-spike interval histogram, revealed stronger encoding of both the fundamental and the lower formant frequencies in fibers of quiet-aged gerbils, but no qualitative changes in vowel encoding. Elevated thresholds in combination with a fixed stimulus level, i.e., lower sensation levels of the stimuli for old individuals, can explain the enhanced temporal coding of the vowels in noise.DiscussionThese results suggest that the altered auditory-nerve discrimination metrics in old gerbils may mask age-related deterioration in the central (auditory) system to the extent that behavioral vowel discrimination matches that of the young adults.

Motion discrimination is essential for animals to avoid collisions, to escape from predators, to catch prey or to communicate. Although most terrestrial vertebrates can benefit by combining concurrent stimuli from sound and vision to obtain a most salient percept of the moving object, there is little research on the mechanisms involved in such cross-modal motion discrimination. We used European starlings as a model with a well-studied visual and auditory system. In a behavioural motion discrimination task with visual and acoustic stimuli, we investigated the effects of cross-modal interference and attentional processes. Our results showed an impairment of motion discrimination when the visual and acoustic stimuli moved in opposite directions as compared to congruent motion direction. By presenting an acoustic stimulus of very short duration, thus lacking directional motion information, an additional alerting effect of the acoustic stimulus became evident. Finally, we show that a temporally leading acoustic stimulus did not improve the response behaviour compared to the synchronous presentation of the stimuli as would have been expected in case of major alerting effects. This further supports the importance of congruency and synchronicity in the current test paradigm with a minor role of attentional processes elicited by the acoustic stimulus. Together, our data clearly show cross-modal interference effects in an audio-visual motion discrimination paradigm when carefully selecting real-life stimuli under parameter conditions that meet the known criteria for cross-modal binding.

Older people often show auditory temporal processing deficits and speech-in-noise intelligibility difficulties even when their audiogram is clinically normal. The causes of such problems remain unclear. Some studies have suggested that for people with normal audiograms, age-related hearing impairments may be due to a cognitive decline, while others have suggested that they may be caused by cochlear synaptopathy. Here, we explore an alternative hypothesis, namely that age-related hearing deficits are associated with decreased inhibition. For human adults (N = 30) selected to cover a reasonably wide age range (25-59 years), with normal audiograms and normal cognitive function, we measured speech reception thresholds in noise (SRTNs) for disyllabic words, gap detection thresholds (GDTs), and frequency modulation detection thresholds (FMDTs). We also measured the rate of growth (slope) of auditory brainstem response wave-I amplitude with increasing level as an indirect indicator of cochlear synaptopathy, and the interference inhibition score in the Stroop color and word test (SCWT) as a proxy for inhibition. As expected, performance in the auditory tasks worsened (SRTNs, GDTs, and FMDTs increased), and wave-I slope and SCWT inhibition scores decreased with ageing. Importantly, SRTNs, GDTs, and FMDTs were not related to wave-I slope but worsened with decreasing SCWT inhibition. Furthermore, after partialling out the effect of SCWT inhibition, age was no longer related to SRTNs or GDTs and became less strongly related to FMDTs. Altogether, results suggest that for people with normal audiograms, age-related deficits in auditory temporal processing and speech-in-noise intelligibility are mediated by decreased inhibition rather than cochlear synaptopathy.

The present study establishes the Mongolian gerbil (Meriones unguiculatus) as a model for investigating the perception of human speech sounds. We report data on the discrimination of logatomes (CVCs1 - consonant-vowel-consonant combinations with outer consonants /b/, /d/, /s/ and /t/ and central vowels /a/, /a:/, /ε/, /e:/, /I/, /i:/, /ɔ/, /o:/, /℧/ and /u:/, VCVs2 - vowel-consonant-vowel combinations with outer vowels /a/, /I/ and /℧/ and central consonants /b/, /d/, /f/, /g/, /k/, /l/, /m/, /n/, /p/, /s/, /t/ and /v/) by young gerbils. Four young gerbils were trained to perform an oddball target detection paradigm in which they were required to discriminate a deviant CVC or VCV in a sequence of CVC or VCV standards, respectively. The experiments were performed with an ICRA-1 noise masker with speech-like spectral properties, and logatomes of multiple speakers were presented at various signal-to-noise ratios. Response latencies were measured to generate perceptual maps employing multidimensional scaling, which visualize the gerbils’ internal representations of the sounds. The dimensions of the perceptual maps were correlated to multiple phonetic features of the speech sounds for evaluating which features of vowels and consonants are most important for the discrimination. The perceptual representation of vowels and consonants in gerbils was similar to that of humans, although gerbils needed higher signal-to-noise ratios for the discrimination of speech sounds than humans. The gerbils’ discrimination of vowels depended on differences in the frequencies of the first and second formant determined by tongue height and position. Consonants were discriminated based on differences in combinations of their articulatory features. The similarities in the perception of logatomes by gerbils and humans renders the gerbil a suitable model for human speech sound discrimination. Highlights Perceptual maps of vowels and consonants in Mongolian gerbils are derived Gerbils perceive vowels and consonants in the same way as humans Gerbils discriminate vowels based on frequency differences of the formants Gerbils discriminate consonants based on differences in articulatory features

Schroeder-phase harmonic tone complexes have been used in physiological and psychophysical studies in several species to gain insight into cochlear function. Each pitch period of the Schroeder stimulus contains a linear frequency sweep; the duty cycle, sweep velocity, and direction are controlled by parameters of the phase spectrum. Here, responses to a range of Schroeder-phase harmonic tone complexes were studied both behaviorally and in neural recordings from the auditory nerve and inferior colliculus of Mongolian gerbils. Gerbils were able to discriminate Schroeder-phase harmonic tone complexes based on sweep direction, duty cycle, and/or velocity for fundamental frequencies up to 200 Hz. Temporal representation in neural responses based on the van Rossum spike-distance metric, with time constants of either 1 ms or related to the stimulus' period, was compared with average discharge rates. Neural responses and behavioral performance were both expressed in terms of sensitivity, d', to allow direct comparisons. Our results suggest that in the auditory nerve, stimulus fine structure is represented by spike timing, whereas envelope is represented by rate. In the inferior colliculus, both temporal fine structure and envelope appear to be represented best by rate. However, correlations between neural d' values and behavioral sensitivity for sweep direction were strongest for both temporal metrics, for both auditory nerve and inferior colliculus. Furthermore, the high sensitivity observed in the inferior colliculus neural rate-based discrimination suggests that these neurons integrate across multiple inputs arising from the auditory periphery.

ABSTRACT The mechanisms of sound localization are actively debated, especially which cues are predominately used and why. Our study provides behavioural data in chickens (Gallus gallus) and relates these to estimates of the perceived physical cues. Sound localization acuity was quantified as the minimum audible angle (MAA) in azimuth. Pure-tone MAA was 12.3, 9.3, 8.9 and 14.5 deg for frequencies of 500, 1000, 2000 and 4000 Hz, respectively. Broadband-noise MAA was 12.2 deg, which indicates excellent behavioural acuity. We determined ‘external cues’ from head-related transfer functions of chickens. These were used to derive ‘internal cues’, taking into account published data on the effect of the coupled middle ears. Our estimates of the internal cues indicate that chickens likely relied on interaural time difference cues alone at low frequencies of 500 and 1000 Hz, whereas at 2000 and 4000 Hz, interaural level differences may be the dominant cue.

Acoustic masking reduces the efficiency of communication, prey detection, and predator avoidance in marine mammals. Most underwater sounds fluctuate in amplitude. The ability of harbor porpoises (Phocoena phocoena) to detect sounds in amplitude-varying masking noise was examined. A psychophysical technique evaluated hearing thresholds of three harbor porpoises for 500-2000 ms tonal sweeps (3.9-4.1 kHz), presented concurrently with sinusoidal amplitude-modulated (SAM) or unmodulated Gaussian noise bands centered at 4 kHz. Masking was assessed in relation to signal duration and masker level, amplitude modulation rate (1, 2, 5, 10, 20, 40, 80, and 90 Hz), modulation depth (50%, 75%, and 100%) and bandwidth (1/3 or 1 octave). Masking release (MR) due to SAM was assessed by comparing thresholds in modulated and unmodulated maskers. Masked thresholds were affected by SAM rate with the lowest thresholds (i.e., largest MR was 14.5 dB) being observed for SAM rates between 1 and 5 Hz at higher masker levels. Increasing the signal duration from 500-2000 ms increased MR by 3.3 dB. Masker bandwidth and depth of modulation had no substantial effect on MR. The results are discussed with respect to MR resulting from envelope variation and the impact of noise in the environment.

Loss of inner hair cell-auditory nerve fiber synapses is considered to be an important early stage of neural presbyacusis. Mass potentials, recorded at the cochlear round window, can be used to derive the neural index (NI), a sensitive measure for pharmacologically-induced synapse loss. Here, we investigate the applicability of the NI for measuring age-related auditory synapse loss in young-adult, middle-aged, and old Mongolian gerbils. Synapse loss, which was progressively evident in the 2 aged groups, correlated weakly with NI when measured at a fixed sound level of 60 dB SPL. However, the NI was confounded by decreases in single-unit firing rates at 60 dB SPL. NI at 30 dB above threshold, when firing rates were similar between age groups, did not correlate with synapse loss. Our results show that synapse loss is poorly reflected in the NI of aged gerbils, particularly if further peripheral pathologies are present. The NI may therefore not be a reliable clinical tool to assess synapse loss in aged humans with peripheral hearing loss.

Informational masking emerges with processing of complex sounds in the central auditory system and can be affected by uncertainty emerging from trial-to-trial variation of stimulus features. Uncertainty can be non-informative but confusing and thus mask otherwise salient stimulus changes resulting in increased discrimination thresholds. With increasing age, the ability for processing of such complex sound scenes degrades. Here, 6 young and 4 old gerbils were tested behaviorally in a vowel discrimination task. Animals were trained to discriminate between sequentially presented target and reference vowels of the vowel pair/I/-/i/. Reference and target vowels were generated shifting the three formants of the reference vowel in steps towards the formants of the target vowels. Non-informative but distracting uncertainty was introduced by random changes in location, level, fundamental frequency or all three features combined. Young gerbils tested with uncertainty for the target or target and reference vowels showed similar informational masking effects for both conditions. Young and old gerbils were tested with uncertainty for the target vowels only. Old gerbils showed no threshold increase discriminating vowels without uncertainty in comparison with young gerbils. Introducing uncertainty, vowel discrimination thresholds increased for young and old gerbils and vowel discrimination thresholds increased most when presenting all three uncertainty features combined. Old gerbils were more susceptible to non-informative uncertainty and their thresholds increased more than thresholds of young gerbils. Gerbils’ vowel discrimination thresholds are compared to human performance in the same task (Eipert et al., 2019).

In the analysis of acoustic scenes, we easily miss sounds or are insensitive to sound features that are salient if presented in isolation. This insensitivity that is not due to interference in the inner ear is termed informational masking (IM). So far, the cellular mechanisms underlying IM remained elusive. Here, we apply a sequential IM paradigm to humans and gerbils using a sound level increment detection task determining the sensitivity to target tones in a background of standard (same frequency) and distracting tones (varying in level and frequency). The amount of IM that was indicated by the level increment thresholds depended on the frequency separation between the distracting and the standard and target tones. In humans and gerbils, we observed similar perceptual thresholds. A release from IM of more than 20 dB was observed in both species if the distracting tones were well segregated in frequency from the other tones. Neuronal rate responses elicited by similar sequences in gerbil inferior colliculus and auditory cortex were recorded. At both levels of the auditory pathway, the neuronal thresholds obtained with a signal-detection-theoretic approach deducing the sensitivity from the analysis of the neurons' receiver operating characteristics matched the psychophysical thresholds revealing that IM already emerges at midbrain level. By applying objective response measures in physiology and psychophysics, we demonstrated that the population of neurons has a sufficient sensitivity for explaining the perceptual level increment thresholds indicating IM. There was a good correspondence between the neuronal and perceptual release from IM being related to auditory stream segregation.