Age-Related Deficits in Binaural Hearing: Contribution of Peripheral and Central Effects.

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.

Cochlear Ribbon Synapses in Aged Gerbils.

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.

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.

Masking release at 4 and 32 kHz in harbor seals associated with sinusoidal amplitude-modulated masking noise.

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.

Neural processing and perception of Schroeder-phase harmonic tone complexes in the gerbil: Relating single-unit neurophysiology to behavior.

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.

Chickens have excellent sound localization ability.

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.

Evidence for the origin of the binaural interaction component of the auditory brainstem response.

The binaural interaction component (BIC) represents the mismatch between auditory brainstem responses (ABR) obtained with binaural stimulation and the sum of ABRs obtained with monaural left and right stimulation. It is generally assumed that the BIC reflects binaural integration. Its potential use as a diagnostic tool, however, is hampered by the lack of direct evidence about its origin. While an origin at the initial site of binaural integration seems likely, there is no general agreement on the contribution of the two primary candidate nuclei, the lateral and medial superior olives (LSO and MSO, respectively). Here, we recorded local field potentials (LFP) and responses of units in the LSO and MSO of Mongolian gerbils (Meriones unguiculatus), presenting clicks with an interaural time or level difference (ITD and ILD, respectively), while simultaneously recording ABR. We determined the BIC from the ABR and, importantly, from LFP and responses of units in the LSO and MSO. If stimulus-induced changes in the ABR-derived BIC have their source in the LSO and/or MSO, we expect coherent changes in the unit-derived and the ABR-derived BIC. We find that BIC obtained from LSO units exhibits the same ITD and ILD dependence as the ABR-derived BIC. Neither BIC obtained from MSO units nor LFP-derived BIC recorded in either LSO or MSO did. The data thus strongly suggest that it is the activity of LSO units in the gerbil that is decisive for the generation of the ABR-derived BIC, determining its properties.

Interaction of spatial and non-spatial cues in auditory stream segregation in the European starling.

Integrating sounds from the same source and segregating sounds from different sources in an acoustic scene are an essential function of the auditory system. Naturally, the auditory system simultaneously makes use of multiple cues. Here, we investigate the interaction between spatial cues and frequency cues in stream segregation of European starlings (Sturnus vulgaris) using an objective measure of perception. Neural responses to streaming sounds were recorded, while the bird was performing a behavioural task that results in a higher sensitivity during a one-stream than a two-stream percept. Birds were trained to detect an onset time shift of a B tone in an ABA- triplet sequence in which A and B could differ in frequency and/or spatial location. If the frequency difference or spatial separation between the signal sources or both were increased, the behavioural time shift detection performance deteriorated. Spatial separation had a smaller effect on the performance compared to the frequency difference and both cues additively affected the performance. Neural responses in the primary auditory forebrain were affected by the frequency and spatial cues. However, frequency and spatial cue differences being sufficiently large to elicit behavioural effects did not reveal correlated neural response differences. The difference between the neuronal response pattern and behavioural response is discussed with relation to the task given to the bird. Perceptual effects of combining different cues in auditory scene analysis indicate that these cues are analysed independently and given different weights suggesting that the streaming percept arises consecutively to initial cue analysis.

Release from informational masking by auditory stream segregation: perception and its neural correlate.

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.

Processing of interaural phase differences in components of harmonic and mistuned complexes in the inferior colliculus of the Mongolian gerbil.

Harmonicity and spatial location provide eminent cues for the perceptual grouping of sounds. In general, harmonicity is a strong grouping cue. In contrast, spatial cues such as interaural phase or time difference provide for strong grouping of stimulus sequences but weak grouping for simultaneously presented sounds. By studying the neuronal basis underlying the interaction of these cues in processing simultaneous sounds using van Rossum spike train distance measures, we aim at explaining the interaction observed in psychophysical experiments. Responses to interaural phase differences imposed on single components of harmonic and mistuned complex tones as well as noise delay functions were recorded as multiunit responses from the inferior colliculus of Mongolian gerbils. Results revealed a better representation of interaural phase differences if imposed on a harmonic rather than a mistuned frequency component of a complex tone. The representation of interaural phase differences was better for long integration-time windows approximately reflecting firing rates rather than short integration-time windows reflecting the temporal pattern of the stimulus-driven response. We found only a weak impact of interaural phase differences if combined with mistuning of a component in a harmonic tone complex.

Interaction of interaural cues and their contribution to the lateralisation of Mongolian gerbils (Meriones unguiculatus).

The main sound localisation cues in the horizontal plane are interaural time and level differences (ITDs and ILDs, respectively). ITDs are thought to be the dominant cue in the low-frequency range, ILDs the dominant cue in the high-frequency range. ITDs and ILDs co-occur. Their interaction and contribution to the lateralisation of pure tones by Mongolian gerbils was investigated behaviourally using cross-talk cancellation techniques for presenting ITDs and ILDs independently. First, ITDs were applied to pure tones with frequencies ≤ 2 kHz to the ongoing waveform, at the onsets and offsets, or in both the ongoing waveform and at the onsets and offsets. Gerbils could lateralise tones only if ongoing ITDs were present indicating that ongoing ITDs are decisive for the lateralisation of low-frequency tones. Second, an ITD was added to 2-to-6-kHz tones with varying ILD. Gerbils' lateralisation was unaffected by the ITD indicating that a large ILD provides a strong lateralisation cue at those frequencies. Finally, small ILDs were applied to 2-kHz tones with an ongoing ITD, pointing either to the same or opposing sides as the ITD. Gerbils' lateralisation was driven by the ITD but strongly affected by the ILD indicating that both interaural cues contribute to the lateralisation.

Effect of preceding stimulation on sound localization and its representation in the auditory midbrain.

Prior stimulation can influence the perception of sound source location. Some psychophysical sound localization procedures differ in the amount of prior stimulation, which may affect measures of localization accuracy. If and how particularly the number of preceding stimuli affects sound localization and the neural representation of sound source position has not been investigated so far and will be the focus of the present report. We trained Mongolian gerbils in a left/right discrimination task where the target stimulus was preceded by silence or followed a number of reference stimuli. Localization thresholds decreased with the number of references presented before the target stimulus. The smallest thresholds were found after the presentation of a train of 5 reference stimuli and after silence. We recorded from units in the inferior colliculus (IC) of anaesthetized gerbils using virtual-acoustic space stimuli mimicking the ones used in the behavioural task and applied signal detection theory to compare behavioural and neurometric thresholds. We found that neurometric thresholds based on spike rate information of single units covered a wide range of threshold values but only neurometric thresholds that were based on responses of small populations of IC units reached consistently thresholds we also observed in the behavioural experiment. Unlike behavioural thresholds, however, neurometric thresholds were independent of the number of reference stimuli suggesting that processing stages downstream from the IC might better reflect the effect of prior stimulation.

Neural correlates of auditory streaming in an objective behavioral task.

Segregating streams of sounds from sources in complex acoustic scenes is crucial for perception in real world situations. We analyzed an objective psychophysical measure of stream segregation obtained while simultaneously recording forebrain neurons in the European starlings to investigate neural correlates of segregating a stream of A tones from a stream of B tones presented at one-half the rate. The objective measure, sensitivity for time shift detection of the B tone, was higher when the A and B tones were of the same frequency (one stream) compared with when there was a 6- or 12-semitone difference between them (two streams). The sensitivity for representing time shifts in spiking patterns was correlated with the behavioral sensitivity. The spiking patterns reflected the stimulus characteristics but not the behavioral response, indicating that the birds' primary cortical field represents the segregated streams, but not the decision process.

The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response.

The auditory brainstem response (ABR) is a sound-evoked noninvasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, the authors discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. The authors review how interaural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized.

Moving Objects in the Barn Owl's Auditory World.

Barn owls are keen hunters of moving prey. They have evolved an auditory system with impressive anatomical and physiological specializations for localizing their prey. Here we present behavioural data on the owl's sensitivity for discriminating acoustic motion direction in azimuth that, for the first time, allow a direct comparison of neuronal and perceptual sensitivity for acoustic motion in the same model species. We trained two birds to report a change in motion direction within a series of repeating wideband noise stimuli. For any trial the starting point, motion direction, velocity (53-2400°/s), duration (30-225 ms) and angular range (12-72°) of the noise sweeps were randomized. Each test stimulus had a motion direction being opposite to that of the reference stimuli. Stimuli were presented in the frontal or the lateral auditory space. The angular extent of the motion had a large effect on the owl's discrimination sensitivity allowing a better discrimination for a larger angular range of the motion. In contrast, stimulus velocity or stimulus duration had a smaller, although significant effect. Overall there was no difference in the owls' behavioural performance between "inward" noise sweeps (moving from lateral to frontal) compared to "outward" noise sweeps (moving from frontal to lateral). The owls did, however, respond more often to stimuli with changing motion direction in the frontal compared to the lateral space. The results of the behavioural experiments are discussed in relation to the neuronal representation of motion cues in the barn owl auditory midbrain.

Effects of signal features and background noise on distance cue discrimination by a songbird.

During the transmission of acoustic signals, the spectral and temporal properties of the original signal are degraded, and with increasing distance more and more echo patterns are imposed. It is well known that these physical alterations provide useful cues to assess the distance of a sound source. Previous studies in birds have shown that birds employ the degree of degradation of a signal to estimate the distance of another singing male (referred to as ranging). Little is known about how acoustic masking by background noise interferes with ranging, and if the number of song elements and stimulus familiarity affect the ability to discriminate between degraded and undegraded signals. In this study we trained great tits (Parus major L.) to discriminate between signal variants in two background types, a silent condition and a condition consisting of a natural dawn chorus. We manipulated great tit song types to simulate patterns of reverberation and degradation equivalent to transmission distances of between 5 and 160 m. The birds' responses were significantly affected by the differences between the signal variants and by background type. In contrast, stimulus familiarity or their element number had no significant effect on signal discrimination. Although background type was a significant main effect with respect to the response latencies, the great tits' overall performance in the noisy dawn chorus was similar to the performance in silence.

Amplitude and phase equalization of stimuli for click evoked auditory brainstem responses.

Although auditory brainstem responses (ABRs), the sound-evoked brain activity in response to transient sounds, are routinely measured in humans and animals there are often differences in ABR waveform morphology across studies. One possible reason may be the method of stimulus calibration. To explore this hypothesis, click-evoked ABRs were measured from seven ears in four Mongolian gerbils (Meriones unguiculatus) using three common spectrum calibration strategies: Minimum phase filter, linear phase filter, and no filter. The results show significantly higher ABR amplitude and signal-to-noise ratio, and better waveform resolution with the minimum phase filtered click than with the other strategies.

Azimuthal sound localization in the European starling (Sturnus vulgaris): II. Psychophysical results.

Small songbirds have a difficult analysis problem: their head is small compared to the wavelengths of sounds used for communication providing only small interaural time and level differences. Klump and Larsen (1992) measured the physical binaural cues in the European starling (Sturnus vulgaris) that allow the comparison of acoustical cues and perception. We determined the starling's minimum audible angle (MAA) in an operant Go/NoGo procedure for different spectral and temporal stimulus conditions. The MAA for broadband noise with closed-loop localization reached 17°, while the starling's MAA for open-loop localization of broadband noise reached 29°. No substantial difference between open-loop and closed-loop localization was found in 2 kHz pure tones. The closed-loop MAA improved from 26° to 19° with an increase in pure tone frequency from 1 to 4 kHz. This finding is in line with the physical cues available. While the starlings can only make use of interaural time difference cues at lower frequencies (e.g., 1 and 2 kHz), additional interaural level difference cues become available at higher frequencies (e.g., 4 kHz or higher, Klump and Larsen 1992). An improvement of the starling's MAA with an increasing number of standard stimulus presentations prior to the test stimulus has important implications for determining relative (MAA) localization thresholds.

Why longer song elements are easier to detect: threshold level-duration functions in the Great Tit and comparison with human data.

Our study estimates detection thresholds for tones of different durations and frequencies in Great Tits (Parus major) with operant procedures. We employ signals covering the duration and frequency range of communication signals of this species (40-1,010 ms; 2, 4, 6.3 kHz), and we measure threshold level-duration (TLD) function (relating threshold level to signal duration) in silence as well as under behaviorally relevant environmental noise conditions (urban noise, woodland noise). Detection thresholds decreased with increasing signal duration. Thresholds at any given duration were a function of signal frequency and were elevated in background noise, but the shape of Great Tit TLD functions was independent of signal frequency and background condition. To enable comparisons of our Great Tit data to those from other species, TLD functions were first fitted with a traditional leaky-integrator model. We then applied a probabilistic model to interpret the trade-off between signal amplitude and duration at threshold. Great Tit TLD functions exhibit features that are similar across species. The current results, however, cannot explain why Great Tits in noisy urban environments produce shorter song elements or faster songs than those in quieter woodland environments, as detection thresholds are lower for longer elements also under noisy conditions.

Phase discrimination ability in Mongolian gerbils provides evidence for possible processing mechanism of mistuning detection.

Compared to humans, Mongolian gerbils (Meriones unguiculatus) are much more sensitive at detecting mistuning of frequency components of a harmonic complex (Klinge and Klump. J Acoust Soc Am 128:280-290, 2010). One processing mechanism suggested to result in the high sensitivity involves evaluating the phase shift that gradually develops between the mistuned and the remaining components in the same or separate auditory filters. To investigate if this processing mechanism may explain the observed sensitivity, we determined the gerbils' thresholds to detect a constant phase shift in a component of a harmonic complex that is introduced without a frequency shift. The gerbils' detection thresholds for constant phase shifts were considerably lower for a high-frequency component (6,400 Hz) than for a low-frequency component (400 Hz) of a 200-Hz harmonic complex and increased with decreasing stimulus duration. Compared to the phase shifts calculated from the mistuning detection thresholds, the detection thresholds for constant phase shifts were similar to those for gradual phase shifts for the low-frequency harmonic but considerably lower for the high-frequency harmonic. A simulation of the processing of harmonic complexes by the gerbil's peripheral auditory filters when components are phase shifted shows waveform changes comparable to those assessed for mistuning detection Klinge and Klump (J Acoust Soc Am 128:280-290, 2010) and provides evidence that detection of the gradual phase shifts may underlie mistuning detection.