Publications using the PA5

Acoustic communication signals often contain a complex temporal structure, yet how this temporal structure contributes to signal recognition is poorly understood, particularly in eavesdropping receivers. The parasitoid fly Ormia ochracea localises host crickets by eavesdropping on their calling songs. In Florida, preferred host songs consist of sound pulses repeated at ∼50 pulses s−1, and flies exhibit matching preferences. However, it is unclear whether this preference reflects sensitivity to individual temporal parameters or to derived temporal relationships that emerge from their combination. We independently varied pulse duration and interpulse interval across a broad stimulus space and quantified tethered-walking phonotaxis using a switch-following paradigm. Behavioural responses formed a structured tuning surface, with elevated responses for pulse durations of ∼5–15 ms across a broad range of interpulse intervals, together with high performance along a diagonal corresponding to 50 pulses s−1. Responses failed to collapse across stimuli sharing the same pulse rate or pulse period, indicating that these parameters alone do not determine recognition. Models allowing behavioural responses to vary jointly across combinations of temporal parameters substantially outperformed models based on single parameters. Although pulse duration strongly constrained recognition, behavioural responses also varied systematically with interpulse interval and could not be explained by pulse duration, interpulse interval, pulse rate, pulse period or duty cycle alone. The apparent preference of O. ochracea for ∼50 pulses s−1 therefore represents one component of a broader temporal recognition landscape rather than recognition based on pulse rate alone.

Purpose Otoacoustic emissions (OAEs) are used to assess outer hair cell (OHC) function. Clinical interpretation of OAE responses, however, is often limited to a present/absent binary since both physiological factors and measurement variability affect the measured OAE amplitude. Prior work showed elevated OAE responses in sedated compared to awake chinchillas, pointing to the potential influence of the medial olivocochlear (MOC) efferents on amplitudes, but this finding is inconsistent across species and OAE type. Here, we aimed to further investigate the effect of anesthesia on distortion-and reflection-type emissions in chinchillas using swept stimuli and more reliable calibration methods. Methods Swept distortion-product (DP) and stimulus-frequency (SF) OAEs were measured in chinchillas with and without ketamine/xylazine sedation. Stimuli were presented using in-ear forward pressure level calibrations. DPOAE and SFOAE amplitudes and estimated Q erb from SFOAE group delays were compared across the two conditions. Results We found that low-frequency DPOAE amplitudes were elevated when animals were sedated. The difference in SFOAE amplitudes was more variable across animals but appeared mildly reduced in sedated animals. Q erb estimates were slightly higher in sedated animals at some frequencies. The effect of sedation was not different across sexes. Conclusion Taken together, these findings suggest that sedation impacts OAE measurements in chinchillas. MOC modulation could account for the present findings and differences across species. For diagnostic precision, OAE responses should be considered in the context of not only intrinsic OHC function but also extrinsic physiological processes that can modulate OHCs.

A key feature of vowels in spoken language is that their fundamental frequency ( f 0 ), which underlies perceived pitch, can change dynamically over time. However, it remains elusive how such prosodic glides shape the neural response in the auditory cortex. The current magnetoencephalography (MEG) experiment was designed to study the transient and sustained neuromagnetic correlates of prosodic contour information in vowels, with a particular focus on the P2 component. Twenty-four normal-hearing participants passively listened to vowel sequences in which both vowel type and prosodic contour were either unchanged or varied between successive vowels. At the level of single vowels, the results showed that falling contours elicit larger and earlier P2 responses than rising and flat prosodic contours. At the level of vowel triplets, the P2 was larger in response to stimulus sequences in which prosodic contour was varied across stimuli. The data indicate that the P2 might be a neural correlate of the early processing of prosodic contour information; moreover, they suggest that the P2 might be particularly sensitive to pitch glides, possibly due to longer time constants that are encompassed within the P2.

This study examined whether interaural amplitude modulation (AM) coherence influences binaural pitch fusion in cochlear implant (CI) users. Fourteen adults, including seven bimodal and seven bilateral CI users, completed fusion-range measurements using dichotic stimuli under unmodulated, coherent AM and two incoherent AM conditions involving interaural AM-phase and AM-rate mismatches. Coherent AM consistently broadened fusion ranges, often doubling those in the unmodulated condition, even with shallow modulation depth. In contrast, incoherent AM, including interaural phase or rate mismatches, narrowed fusion. These findings indicate that temporal-envelope coherence facilitates binaural integration in CI users, emphasizing its importance for auditory processing and CI sound-processing design.

Platinum electrodes are used in many bionic devices; however, they have limited charge injection capacity (CIC) and signal‐to‐noise ratio (SNR), restricting performance. Iridium oxide has substantially larger CIC and reduced impedance compared to platinum. While these types of electrochemical measurements are typically used to infer improved electrophysiological performance, there are no studies demonstrating this correlation. This article compares the electrochemical and acute electrophysiological recording performance of iridium and electrochemically activated IrOx. Increased iridium activation reduced total impedance at low‐intermediate frequencies and steady‐state electroactive area but had no impact on linear diffusion electroactive area. The total impedance had a poor correlation with background noise, SNR and spike count. The results contribute to the previous literature indicating linear diffusion electroactive area determines the number of neurons within recording distance of the electrode, impacting SNR and spike count. Measurements of impedance are mainly of benefit as an indirect measure of linear diffusion electroactive area, in which case the measurement and analysis must be performed appropriately. A wide range of IrOx activation states can be produced with increased CIC, without concern of neural recording performance impacts. However, higher oxidation states resulting in electrode dissolution or increase in electrode resistance may limit IrOx chronic performance.

Mutations in Myo7a cause Usher syndrome type 1B and non-syndromic deafness, but the precise function of MYO7A in sensory hair cells remains unclear. Using long-read sequencing, we identify and characterize a novel isoform, MYO7A-N, expressed in auditory hair cells alongside the canonical MYO7A-C. Isoform-specific knock-in mouse models reveal that inner hair cells primarily express MYO7A-C, while outer hair cells express both isoforms in opposing tonotopic gradients. Both isoforms are localized to the upper tip-link insertion site, consistent with a role in the tip link for mechanotransduction. Loss of MYO7A-N leads to outer hair cell degeneration and progressive hearing loss. Cryo-EM structures reveal isoform-specific differences at actomyosin interfaces, correlating with distinct ATPase activities. These findings reveal an unexpected layer of molecular diversity within the mechanotransduction machinery. We propose that MYO7A isoform specialization enables fine-tuning of tip-link tension, thus hearing sensitivity, and contributes to the frequency-resolving power of the cochlea.

Background: Prolonged exposure to moderate and loud noise is known to impair hearing; however, the safety of long-duration exposure to low-level sound, such as that encountered during everyday conversation, remains unclear. This study aimed to determine the effect of continuous exposure to sound at a 65 dB sound pressure level (SPL) on auditory processing. Methods: Auditory brainstem responses (ABRs) were recorded in C57BL/6 mice before and after a 1 h exposure to a continuous pure tone at 65 dB SPL. Changes in ABR thresholds, wave amplitudes, and latencies were analyzed across frequencies and time points. Correlations between amplitude and latency changes across ABR waves were also assessed. Results: Tone exposure induced a significant, frequency-specific increase in ABR thresholds, with a mean elevation of approximately 6 dB and a maximum shift of 15 dB. Significant reductions in amplitudes and prolongations of latencies were observed in Waves I–III, while Wave V amplitude remained relatively stable. A strong negative correlation between amplitude reduction and latency increase was found in Wave I, which progressively weakened from Wave II to Wave V. These functional changes persisted for up to three hours following exposure before gradually returning to baseline. Conclusions: Prolonged exposure to low-level sound at intensities typical of conversational speech can transiently impair auditory function and alter early neural processing in the auditory pathway. These findings suggest that sound levels commonly considered safe may still pose a risk when exposure is sustained, with implications for understanding hidden hearing loss and improving early diagnostic approaches.

Background Peripheral hearing loss is associated with auditory hallucinations and increased risk for psychotic disorder, particularly in genetically vulnerable individuals. Moreover, both hearing loss and schizophrenia disrupt auditory temporal acuity, a sensitive measure of auditory brain function. Here, we used mouse models of hearing loss and schizophrenia to reveal how neural mechanisms of auditory cortical temporal acuity depend on sensory and genetic risk factors for psychosis. Methods We quantified auditory cortical temporal acuity in mice with or without hearing loss and with or without the 22q11.2 deletion — one of the strongest known genetic risk factors for schizophrenia. Cortical single-unit and population activity were recorded in awake mice (N = 23) during presentations of loudness-adjusted gap-in-noise stimuli with varying durations of silent gap, which are commonly used to assess auditory temporal acuity in humans. Results Both hearing loss and the 22q11.2 deletion disrupted auditory cortical temporal acuity, but through distinct mechanisms. Hearing loss broadly degraded temporal acuity at the level of single-unit responses and neural population activity. In contrast, the 22q11.2 deletion selectively impaired gap duration thresholds in regular-spiking (putative excitatory) but not fast-spiking (putative inhibitory) neurons. Mice with comorbid hearing loss and 22q11.2 deletion exhibited both abnormalities in auditory cortical temporal acuity. Conclusions Sensory and genetic risk factors for psychosis can disrupt auditory cortical temporal acuity via distinct mechanisms that remain partially dissociable even under comorbid conditions. These findings underscore the importance of accounting for hearing loss comorbidity when interpreting auditory cortical dysfunction in psychotic disorder.

Male bushcrickets produce complex species-specific songs to attract mating partners. Since the neuronal processing underlying song-pattern detection is not fully understood, we analysed extracellularly recorded song-induced spike responses and local field potentials across the first stage of auditory processing in the prothoracic ganglion of Mecopoda elongata. We analysed the influence of the temporal structure and of any change in amplitude of spiking and local field potentials. We presented the complete chirp and compared the neuronal response pattern with those responses evoked individually by each pulse of the chirp. Our data revealed: (i) the complete chirp leads to a transient summation in local field potentials over the time course of the chirp, and (ii) significantly fewer action potentials occur during the chirp presentation than to the individually presented pulses. Our data provide insights into the question of how an acoustical signal can be used to extract those features from sensory information that are important for auditory behaviour, such as chorus formation, species recognition, or phonotaxis.

In the auditory cortex, neural responses to stimuli inside receptive fields (RFs) can be further facilitated by behavioral demands, such as attending to a spatial location. It is less clear how off-RF stimuli modulate neural responses and contribute to behavioral tasks. Our recent study revealed a particular form of location-specific facilitation evoked by repeated stimulation from an off-RF location, suggesting behavioral modulation of spatial RFs. To further explore this question, we trained marmosets to attend to sound locations that were either inside or outside the RFs of auditory cortical neurons. The majority of neurons showed increased firing rates at target locations inside their RFs. Interestingly, this increase also occurred outside the RFs, sometimes exceeding the responses at the RF center during passive listening. This task-related off-RF facilitation was much more common in the caudal area than in the rostral area and the primary auditory cortex. A normalization model reproduced the off-RF facilitation using widespread suppression. The model’s prediction was confirmed by experimental observations of widespread reductions in firing rate and hyperpolarized membrane potentials for off-RF stimuli. These results suggest that behavioral task demands recruit a broader range of neurons than those that are responsive to a target sound in the passive state.

The acoustic flutter is processed through complementary monotonic rate coding and cannot be modulated by other acoustic parameters in the auditory cortex (AC). However, it remains unclear how the inferior colliculus (IC) encodes acoustic flutter, especially when changing other acoustic parameters. Here, we recorded IC neural activity in response to acoustic flutter and determined the existence of conjunctive processing between repetition rate and other acoustic parameters. We found that most IC neurons also encode the repetition rate at the flutter range through complementary monotonic rate coding. In addition, although the acoustic parameters did not change their monotonicity, most IC neurons encode both repetition rate and other acoustic parameters, different from the flutter processing in AC. Thus, complementary monotonic rate coding for acoustic flutter was widespread in the auditory system; however, coding specificity for repetition rate increased from IC to AC, and the capacity for conjunctive coding with other acoustic parameters decreased.

BACKGROUND: Noise-induced hearing loss (NIHL) has been traditionally attributed to outer hair cell (OHC) damage, but synaptic injury at inner hair cell (IHC)–spiral ganglion neuron (SGN) junctions may better explain persistent functional deficits. OBJECTIVE: To test whether IHC ribbon loss and functional synapse loss scale with pathological noise intensity and to define their longitudinal relationship to hearing function. METHODS: A rodent NIHL model was exposed to 100 dB SPL for 2 h or 110 dB SPL for 4 h. Cochleae were immunolabeled for CtBP2 (presynaptic ribbons) and GluA2 (postsynaptic AMPA receptor puncta). Putative functional synapses were quantified as closely apposed CtBP2/GluA2 pairs. Hearing function was assessed longitudinally and correlated with synaptic measures. RESULTS: Both exposure conditions produced graded reductions in IHC ribbon counts and CtBP2/GluA2 pairs, with greater losses after 110 dB/4 h. The number of CtBP2/GluA2 apposed pairs closely tracked preserved hearing function, providing a stronger association with functional outcome than ribbon counts alone. Ribbon loss remained largely stable across post-exposure intervals, whereas functional synapse loss was disproportionately larger at early time points, consistent with transient pre–post misalignment. Over time, CtBP2/GluA2 pairing partially recovered toward levels predicted by surviving ribbons, suggesting re-alignment or reconnection of a subset of remaining synaptic elements. CONCLUSION: Pathological noise intensity drives exposure-dependent IHC synaptopathy in addition to OHC injury. Functional synapse counts (CtBP2/GluA2 pairs) sensitively reflect stored hearing function and indicate a potential post-exposure window for synaptic re-establishment.

Harmonicity is a property of complex sounds such as vocalizations or music, but it remains unclear how harmonicity is processed in the auditory cortex (ACtx). Subregions of ACtx are thought to process harmonic stimuli differently. Selective responses to sound features in ACtx emerge hierarchically from primary ACtx (A1) L4 and secondary ACtx (A2) layer (L)2/3, which is believed to be the most responsive to harmonic sounds. Since harmonic stacks can range from 2 to >10 components, being more similar to naturalistic vocalizations, harmonic sensitivity might also arise hierarchically across layers and areas. We studied responses to harmonic stacks of 2–10 frequencies across A1 L4, A1 L2/3, and A2 L2/3 in adult male and female mice using in vivo two-photon microscopy. We found harmonic-sensitive neurons (HNs) responding only to harmonic stacks but not to individual frequencies in all areas at similar proportions. HNs showed highly nonlinear spectral integration of harmonic frequencies that decreased as the harmonic stacks became more complex. Specifically, onset-biased HNs showed greater nonlinearity than offset-biased HNs only in A1 L4. Moreover, HNs in A1 L4 exhibited higher signal correlation than A2 L2/3. Sound-responsive neurons in A1 L4 have the weakest noise correlation compared with A1 L2/3 and A2 L2/3. Together, harmonic sensitivity is not a unique feature of A2 L2/3 but is already established in A1 L4, where neurons robustly encode harmonic sounds through sparse connections.

Cell types are the basic units of the cerebral cortex. Broad and narrow spike waveforms (BW and NW) are the primary criteria for classifying putative excitatory and inhibitory cortical neurons, particularly in non-human primates where genetic accessibility is limited. We have classified cell types in the auditory cortex of marmosets using spike waveforms and firing patterns and identified a new type of neuron: the NW-burst neuron. NW-burst neurons are excitatory, as they drive but do not suppress the firing of connected neurons. Furthermore, NW-burst neurons displayed shorter response latencies, lower response variability, smaller receptive fields, stronger correlations between spatial and non-spatial selectivity, and higher decoding accuracy than other neurons. Together, these findings suggest that cortical NW-burst neurons in non-human primates represent a distinct excitatory cell type. Significance Statement Classifying cell types in non-human primates is challenging due to limited genetic tools. Traditionally, neurons with narrow spikes are assumed to be inhibitory. Challenging this view, we analyzed 1,816 high-quality single units in the marmoset auditory cortex and discovered that narrow-spike burst-firing neurons were excitatory. These neurons exhibited shorter response latencies, smaller receptive fields, and higher decoding accuracy. Crucially, they showed a positive correlation between "where" and "what" selectivity, defying the standard trade-off between spatial and non-spatial response properties. These findings reveal a specific excitatory cell type in the auditory cortex of a non-human primate species that integrates sound information with high temporal fidelity and feature selectivity.

Proper orientation of the apical cytoskeleton in auditory and vestibular hair cells is essential for their sensory function. A recently identified regulator of hair cell orientation is the G protein-coupled receptor GPR156, which signals through inhibitory heterotrimeric G proteins. In hair cells expressing the transcription factor EMX2, GPR156 is apically enriched and polarized at cell junctions. There, GPR156 signaling reverses the interpretation of tissue-level core planar cell polarity cues, effectively reversing the orientation of Emx2 -positive compared to Emx2 -negative hair cells. This mechanism establishes key anatomical features, such as the correct alignment of auditory outer hair cells and the line of polarity reversal in the otolith organs of the vestibular system. Null mice with constitutive Gpr156 inactivation exhibit severe hearing loss, mirroring congenital hearing impairment in human patients with homozygous GPR156 variants. These null mutants also display impaired swimming and vestibulo-ocular reflexes, although the nature of these vestibular deficits differs from those reported in Emx2 mutants. Here, to determine the extent to which functional deficits arise from hair cell misorientation, we conditionally inactivated Gpr156 in postmitotic hair cells in the inner ear. This targeted deletion approach recapitulated the misorientation phenotype observed in null mutants. Notably, 30–40% of cochlear and utricular hair cells affected in the null background retained normal orientation in conditional mutants, likely due to the later timing of Gpr156 inactivation. Despite reduced efficiency, conditional mutants exhibited similar, albeit predictably milder, auditory and vestibular dysfunction. As hair cells can carry out mechano-electrical transduction without GPR156, we conclude that sensory deficits mainly result from its essential role in hair cell orientation.

Deep neural network (DNN)-based noise reduction has emerged as a promising advancement in hearing aid signal processing as a means to improve speech intelligibility in noisy environments for hearing aid wearers. The aim of this study was to investigate the impact of the DNN on speech intelligibility in speech-shaped noise (SSN) and multitalker babble (MTB) when the target speech was coming from the front and from the side. Subjective ratings of clarity, total impression, listening effort, and background noise awareness were also collected. Twenty adult participants with mild to moderately severe sensorineural hearing loss were fitted with hearing aids from a single manufacturer, programmed with four different settings that varied across combinations of microphone directionality (omnidirectional and directional beamforming) and noise reduction (off, traditional, DNN). Results showed that DNN, when combined with beamforming, consistently outperformed the other programs across all metrics. Outcomes were influenced by both noise type and spatial configuration. DNN was more effective in SSN than MTB. Beamforming was especially beneficial when the target speech came from the front. Listening in programs that included both DNN and beamforming together resulted in additional benefits shown in the outcome measures, most likely due to the beamforming improving the signal-to-noise ratio and providing a cleaner signal for the DNN to work with.

No pharmacological interventions exist that can restore or preserve auditory function in the mammalian cochlea. Auditory hair cells (HCs) do not spontaneously regenerate, leading to permanent hearing loss. In non-mammalian vertebrates, HC regeneration happens through proliferation and differentiation of their clonally related supporting cells (SCs). The present study supports the potential of quinoxaline (Qx), a nonsteroidal anti-inflammatory compound, to stimulate SC proliferation in the auditory sensory epithelium, a process that may prime the tissue for future HC regeneration. We synthesized a series of Qx derivatives by introducing various substitutions, ranging from hydrophilic to lipophilic. Seventy analogs were generated and tested in vitro and in vivo. Among those, only one (Qx-100) exhibited the best medicinal chemistry profile and was further modified to expand the structure–activity relationship of the chemotype, develop additional analogs, and optimize potency, bioavailability, and in vivo efficacy. Ten new lead variants were generated. Of those, Qx-294 and Qx-301 demonstrated promising in vitro Absorption, Distribution, Metabolism, and Excretion (ADME) profiles and were selected for further testing. Overall, both compounds were rapidly absorbed in zebrafish and mice and promoted cell proliferation in vitro and in vivo without signs of apoptosis, supporting their potential for sensory HC regeneration.

As the Arctic warms and becomes more accessible to human activities and associated noise sources, it is important to understand the auditory capabilities of ice-associated marine mammals that rely on sound. In this study, the in-air hearing of one adult bearded seal ( Erignathus barbatus ) was measured in ambient outdoor conditions using psychophysical methods. 50% detection thresholds were measured for 10 frequencies (0.04–51.2 kHz) that extend across the subject’s hearing range. For low to mid frequencies (0.04–12.8 kHz), thresholds were constrained, or masked, by ambient noise. Thresholds obtained at higher frequencies (25.6–51.2 kHz) were sufficiently elevated above background noise to provide absolute measures of hearing sensitivity. These measurements reveal that the high-frequency roll-off for bearded seals is in alignment with available auditory data for related species despite more than 11 million years of evolutionary isolation. Further, the data collected at low and mid frequencies enable an unconventional estimation of critical ratios, which can be applied in masking models. Collectively, these findings for bearded seals listening for airborne sounds highlight auditory similarities within the northern clade of phocid Carnivores and improve predictions of potential noise effects for seals in changing Arctic soundscapes.

Introduction Bilateral cochlear implants (BiCIs) do not restore sound localization abilities to the full extent exhibited by typical hearing (TH) listeners, partly due to poor encoding of interaural time differences (ITDs). ITD cues have been provided and investigated using synchronized research processors that ensure the precise delivery of ITD cues. These studies have been conducted in a direct stimulation setting, which bypasses the processor microphones and, in most cases, removes interaural level difference cues (ILDs). To our knowledge, this is the first study that evaluated the efficacy of synchronized stimulation in restoring sensitivity to ITDs in a free field localization experiment. This was made possible by the CCi-MOBILE, a portable and real-time processing research platform that allows for synchronizing microphone inputs. Methods Fourteen BiCI listeners were tested with experimental real-time coding strategies in comparison to unsynchronized clinical processors. We calculated the binaural cues from the acoustic stimuli at the level of microphone input. Results The recordings show that the experimental coding strategies in this study deliver ITDs with greater precision than the clinical strategy. However, psychophysical testing did not show the benefit of an ITD-encoding strategy in improving localization in a free field. The ITD encoding strategies preserved ITDs, which better differentiated unique loudspeaker locations than interaural level differences (ILDs), suggesting that listeners could achieve improved performance if they accessed these cues. As expected, ILDs were similar across all strategies, including the ITD encoding strategies. The lack of improvement in localization performance is likely because ILDs remained to be the dominant cue in acute localization testing, even when ITD cues were available. Discussion Providing BiCI listeners with adequate experiences with ITD cues may be necessary to shift their reliance from ILD dominance to a combined reliance on ILD and ITD cues in free-field conditions. The CCi-MOBILE could enable take-home practice with novel stimulation strategies for extended experiences and long-term evaluation in real-world listening environments.

We describe here a mode of activity of neurons in auditory cortex of freely moving rats consisting of large, slow firing rate modulations, which were not driven by sounds, were larger than the sound evoked responses, and were locked to specific time points during the task, similar to responses of hippocampal time-sensitive neurons. This activity mode had important functional consequences to sound processing during task performance. We show that the slow firing rate modulations caused the ongoing activity just before sound presentations to be higher during task performance than during passive listening. Concurrently, during task performance, the responses to target stimuli were weaker but more informative about the task-relevant sounds. In a model, higher ongoing activity caused more synaptic depression of the cortico-cortical synapses, reducing the tendency of the network to produce population spikes and resulting in weaker but more informative responses to sounds.