Psychoacoustics publications

Many neurological and psychiatric disorders stem from maladaptive conditioning and resist treatment. Tinnitus, as one example, is the distressing perception of sound in the absence of an external source. One of the network systems implicated in multiple disorders is the 'salience network', associated with positive/negative reward, habit formation, motivation, valuation and mood. However, it is not known whether directly modulating the 'salience network' at its anatomical and physiological core, in the ventral striatum, more specifically the nucleus accumbens, could be beneficial. Here we show that a novel treatment approach, targeting the salience network, can reduce tinnitus perception in a rat model. We found that bilateral rewarding stimulation of the nucleus accumbens, when paired with non-tinnitus tones, was most effective. A combined approach using rewarding accumbens stimulation and dysrewarding lateral habenula stimulation - paired with non-tinnitus and tinnitus tones, respectively - also suppressed tinnitus but caused negative effects. Our results demonstrate how the rewarding stimulation can recondition brain networks to effectively remove the salience of tinnitus frequencies. We anticipate that our unique reconditioning strategy has broader therapeutic applications for other brain disorders rooted in maladaptive learning.

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.

It is widely accepted that tinnitus arises from maladaptive neuroplasticity in the central auditory system, which compensates for reduced peripheral input; notably, the loss of inner hair cell (IHC) synapses is considered a key underlying factor. IHC synapses can immediately and permanently degenerate after noise exposure, independent of hair cell loss, whereas the cell bodies and central projections of cochlear neurons can survive for months to years, providing an extended therapeutic window for improving afferent input through synapse regeneration. Using NHPN-1010 (a combination of 2,4-disulfophenyl-N-tert-butylnitrone and N-acetylcysteine), we propose a delayed treatment strategy (≥ 4 weeks after trauma) for noise-induced tinnitus (NIT) in rats. NHPN-1010 enhanced gap-prepulse inhibition of acoustic startle responses-indicative of diminished tinnitus-like deficits-coupled with a concomitant upregulation of GABAergic inhibition in the dorsal cochlear nucleus, relative to vehicle alone (saline). Furthermore, NHPN-1010, compared to saline, led to increased wave-I amplitudes of auditory brainstem responses, the effect accompanied by a corresponding rise in the number of presynaptic ribbons in IHCs. Our findings suggest that NHPN-1010 plays a therapeutic role in NIT by promoting cochlear synaptogenesis and normalizing central auditory signaling.

Alzheimer's disease (AD) is a brain condition with heterogeneity in disease progression due to genetic and environmental variables. There is a critical need to better understand the relationship of AD pathologies and potential modifiable factors like hearing loss. Auditory processing measurements in AD mouse models have been reported, but the results are mixed. Most were conducted using evoked potential recordings measured under anesthesia, unlike typical hearing assessments on aging adult humans. Here, we used operant conditioning and signal detection theory to measure daily pure tone behavioral detection throughout the lifespan of trained mutant and wild-type (WT) control APP/PS1 (on a C57BL/6J background) and 5xFAD (on a C57/SJL background) mice. At the conclusion of operant testing, auditory brainstem response (ABR) measures were taken on the same subjects to determine if evoked potentials provided accurate estimates of perceptual abilities. Behavioral detection worsened significantly across the lifespan in APP/PS1 mice, but there were no differences between mutant and WT mice. For 5xFAD mice, behavioral thresholds generally worsened over the lifespan but with substantial variability, which may be explained by genetic heterogeneity among the background strain. There were no differences between 5xFAD mutant and WT mice. ABR hearing threshold estimates generally matched behavioral findings, with APP/PS1 having significantly worse thresholds than 5xFAD mice but no within-model differences between mutants and WTs. The within-subject differences between behavioral and ABR thresholds ranged from <1 dB to over 40 dB across subjects, suggesting physiological measurements of auditory function are not necessarily reflective of an animal's acoustic perception.

Objective: Perceived voice quality (VQ) ratings provide data with ordinal characteristics on arbitrary scales regarding the relative order of VQ disruptions ranging from mild to severe quality. The overarching goal of this research is to develop a new and rigorous method for perceptual evaluation of VQ using quantitative comparisons and facilitating standardized comparisons across time points, clinicians, and clinical sites. Our prior research developed standard ratio-level scales of breathy and rough VQ analogous to the sone scale that (a) have physical units, (b) are strongly related to psychophysical measures, and (c) can quantify not just the direction but also the magnitude of change. The current study reestablishes the standard reference points, validates the newly developed VQ scales with natural dysphonic stimuli, and evaluates the psychometric measurement properties of the novel scales for breathiness and roughness in a small clinical pilot experiment. Method: In the first experiment, a set of magnitude estimation (ME) tasks were first used to determine the perceived magnitudes of breathiness and roughness of 10 natural voice stimuli in each VQ continuum. The resulting data were compared with previously acquired magnitude estimates of the synthetic comparison stimuli to adjust the reference points. In the second experiment, a set of inexperienced listeners evaluated the same set of natural dysphonic stimuli using the new clinical scales with perceived magnitude expressed in standard VQ units. In the third experiment, two expert clinicians evaluated 12 breathy and 10 rough dysphonic voices (pre- and posttreatment) using the new VQ scales. Results: The standard reference units were identified as 15 dB SNR for breathiness and −26 dB modulation depth for roughness. The strength of the relationship between the ME data and the predicted values from the clinical scales was high for both breathiness and roughness ( r > .9). Treatment outcomes measured using the newly developed scales demonstrated high intra- ( r > .8) and interrater reliability ( r > .8) when compared to Consensus Auditory-Perceptual Evaluation of Voice providing evidence for concurrent validity of the clinical scales. Conclusion: Such formal VQ scales support valid quantitative comparisons of perceptual judgments and represent a critical step in clinical translation.

Astrocytes control neural communications by influencing GABAergic transmission through uptake and synthesis of GABA. Impaired GABAergic signaling is thought to underlie cortical hyperexcitability in autism. Here we show that dysregulation of astrocyte GABA transport in Fragile X syndrome (FXS), a leading genetic cause of autism, contributes to circuit hyperexcitability. Human FXS astrocytes derived from patient-specific induced pluripotent stem cells and mouse Fmr1 knockout (KO) astrocytes display a significant increase in levels of GABA and GABA-synthesizing enzyme GAD65/67. Our astrocyte-specific Fmr1 KO (cKO) mouse model reveals reduced inhibitory connectivity and impaired cortical responses to sound. Abnormal GABA transport in cortical astrocytes contributes to impaired fidelity of temporal processing and abnormal behaviors in cKO mice. Blocking astrocyte GABA transport enables higher PV expression, improves EEG responses to frequency-modulated sound, and corrects aberrant exploratory behavior. Our findings suggest astrocyte GABA transport plays a key role in regulating cortical inhibition, and contributes to autism-associated phenotypes.

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. We found that PVNs act like a volume knob in the mouse auditory cortex (ACtx), bi-directionally adjusting neural and perceptual sensitivity to sound level over a 20 dB range. PVN-based gain adjustments were "sticky," such that a single bout of PVN activation at 40 Hz-but not at 1 or 70 Hz-sustainably dampened ACtx sound responsiveness, enhanced feedforward inhibition, and behaviorally desensitized mice to loudness. We then developed a mouse model of adult-onset hyperacusis by demonstrating ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity following a restricted noise-induced cochlear lesion. We found that several minutes of 40-Hz PVN stimulation in noise-exposed mice sustainably dampened ACtx hyperactivity and restored normal loudness sensitivity for 1 week. These findings demonstrate that sensory disorders caused by permanent peripheral injuries can be reversed by patterned stimulation of cortical circuits that directly regulate perception.

Objective: The vibratory source for voicing in children with dysphonia is classified into three categories including a glottal vibratory source (GVS) observed in those with vocal lesions or hyperfunction; supraglottal vibratory sources (SGVS) observed secondary to laryngeal airway injuries, malformations, or reconstruction surgeries; and a combination of both glottal and supraglottal vibratory sources called mixed vibratory source (MVS). This study evaluated the effects of vibratory source on three primary dimensions of voice quality (breathiness, roughness, and strain) in children with GVS, SGVS, and MVS using single-variable matching tasks and computational measures obtained from bio-inspired auditory models. Methods: A total of 44 dysphonic voice samples from children aged 4-11 years were selected. Seven listeners rated breathiness, roughness, and strain of 1000-ms /ɑ/ samples using single-variable matching tasks. Computational estimates of pitch strength, amplitude modulation filterbank output, and sharpness were obtained through custom-designed MATLAB algorithms. Results: Perceived roughness and strain were significantly higher in children with SGVS and MVS compared to children with GVS. Among the computational measures, only the modulation filterbank output resulted in significant differences among vibratory sources; a posthoc test revealed that children with SGVS had greater amplitude modulation than children with GVS, as expected from their rougher voice quality. Conclusions: The results indicate that the output of an auditory amplitude modulation filterbank model may capture characteristics of SGVS that are strongly related to the rough voice quality.

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.

Everyday listening often requires the auditory system to move beyond the perception of individual sound sources towards a more global representation of acoustic scenes. While auditory behaviour has been well characterised for one or a few sources, it remains unclear how listeners perceive scenes containing many simultaneous sounds. As multiple sound sources combine into a single acoustic mixture, separating individual sources becomes increasingly difficult, potentially requiring listeners to rely on summary representations rather than discrete object-based parsing. Auditory numerosity judgement , the ability to estimate how many distinct sound sources are present, can provide a way to probe how listeners perceive such complex acoustic scenes. Here, we measured numerosity judgements along the three dimensions of auditory space: azimuth, elevation, and distance, allowing each spatial axis to be examined in isolation. As these dimensions rely on markedly different spatial cues and differ strongly in spatial acuity, this design enabled the dissociation of spatial and non-spatial contributions to numerosity perception. Across dimensions, numerosity judgements showed no systematic relationship with individual spatial hearing performance. Speech intelligibility likewise exerted only a weak influence. In contrast, perceived numerosity was significantly modulated by the spectrotemporal coverage of the acoustic mixture, a summary statistic independent of spatial dimension or higher-lever linguistic factors. Together, these findings suggest that auditory numerosity judgement is largely insensitive to spatial hearing precision and instead reflects more general principles of how complex sound mixtures are represented at the scene level.

Introduction: Hearing is critical for communication and clinical evidence suggests that hearing loss can lead to poorer mental well-being including social isolation, anxiety, depression, and cognitive decline. Deaf animal models offer opportunities to investigate the impact of hearing loss on behavioral correlates of mental health while controlling for genetic variability and shared etiological factors such as environmental stressors, aging, and metabolic diseases. We previously showed that conditional deletion of Ebf1 in the inner ear causes deafness. We hypothesize that otic-specific Ebf1 knockout (KO) mice recapitulate neurobehavioral alterations experienced in congenital deafness. Methods: Slc26a9P2A-Cre and Ebf1 floxed mice were crossed previously to generate the otic-specific Ebf1 conditional KO. We measured auditory brainstem response and behavior in groups of otic-specific Ebf1 conditional KO mice and Cre-negative littermate controls (WT). We performed behavioral tests including elevated plus maze, acoustic startle, locomotor activity, forced swim, and Y-maze. Results: We found that the KO mice spend significantly less time than WT mice in the open arms of the elevated plus maze. KO mice also show significantly increased latency to enter the open arms. Acoustic startle response was decreased in KO mice vs. WT controls and pre-pulse inhibition was also reduced in the KO, consistent with elevated hearing thresholds. We found no significant differences in exploratory behavior, forced swim immobility time, or other behavioral measures examined. Conclusions: Our findings demonstrate that deaf otic-specific KO mice are indeed a model for the study of effects of hearing loss on clinically relevant behavioral correlates. Our results provide new empirical evidence that hearing loss contributes to anxiety, which is consistent with clinical evidence that anxiety is associated with hearing loss in older adults.

The Mongolian gerbil is a common model organism for studying the neural and behavioral mechanisms of binaural and spatial hearing, largely because of its ability to hear lower frequencies better than other rodents and thus utilize both interaural time and level difference cues for sound localization. Prior spatial hearing studies in gerbils have relied on operant conditioning paradigms, requiring large amounts of time-consuming training and testing on multiple different tasks needed to make a comprehensive assessment of spatial hearing ability (including temporal processing, spatial acuity and spatial unmasking). This limits the ability of researchers to thoroughly assess behavioral performance in a population of animals. In this study, we used the prepulse inhibition of the acoustic startle reflex (PPI) to extensively assess spatial hearing and temporal processing abilities in a population of gerbils of both sexes. Results show that gerbils inhibit a startle response to a brief loud sound based on prepulse acoustical cues consisting of a 1) temporal gap in ongoing sounds, 2) change in sound source location, and 3) target sound in the presence of a masker. In each test, the magnitude of the suppression of startle increased monotonically as a function of the magnitude of the acoustical prepulse, not unlike a psychometric function, from which threshold performance could be measured. Thresholds in the gerbils in each task measured using PPI matched those acquired using operant conditioning methods.

Background DFNB16, the second most common genetic cause of hearing loss, is caused by mutations of the STRC gene encoding stereocilin, a protein essential for the effective functioning of outer hair cells (OHCs) as cochlear amplifiers. Strc −/− mice, which lack stereocilin, display severe to profound deafness and constitute a relevant preclinical model for DFNB16. Methods Using Strc − / − mice, we developed a gene therapy strategy based on the use of dual AAV9‐PHP.eB vectors to deliver the full‐length Strc cDNA. Therapeutic efficacy was assessed by evaluating stereocilin expression, OHC bundle architecture, and their attachment to the tectorial membrane, together with functional recovery using distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABR) measurements and Go/No‐Go behavioral testing with psychometric analysis. Results Dual‐AAV–mediated Strc gene delivery restored stereocilin expression, OHC bundle architecture and their attachment to the tectorial membrane, leading to the recovery of cochlear amplification and hearing to near normal thresholds, as confirmed by distortion product otoacoustic emission (DPOAE) and auditory brainstem response measurements. Behavioural assessment showed that treated Strc −/− mice regained normal frequency discrimination, indicating a restoration of higher‐order auditory processing, up to 100 days post‐treatment. Conclusion These findings provide the first proof‐of‐principle that peripheral gene therapy can restore OHC function, cochlear amplification and central auditory perception in a DFNB16 model. Key points Dual AAV‐mediated gene delivery restored peripheral hearing in a DFNB16 preclinical mouse model. The same treatment also restored central auditory processing. AAV‐mediated gene therapy represents a promising curative strategy for DFNB16. These results reinforce the translational potential for treating human genetic deafness.

Bilateral cochlear implant (BiCI) users do not perform as well as typical hearing listeners when discriminating the direction of sound motion. This is likely due to the lack of synchronization between two independently operating sound processors. The use of bilaterally linked processors can improve the timing of electrical stimulation across the ears. However, these improvements are potentially counteracted by spectral peak-picking in sound coding strategies that may activate different electrodes across the ears, thereby reducing the fidelity of the binaural cues that BiCI users rely on for sound localization. To improve interaural synchrony, a bilateral peak-picking strategy that guarantees coordinated stimulation across the ears was developed and tested using the CCi-MOBILE, a bilaterally linked research processor. The auditory motion tracking abilities of nine BiCI users were measured using the bilateral peak-picking strategy and compared to performance with commercially available, unsynchronized processors. Results showed no effect of bilateral peak-picking. However, a small benefit was observed when tracking the range of motion of a sound when listening with bilateral synchronization which appears to be due to reduced interaural level difference changes with auditory motion. These findings suggest that dynamic auditory perception with BiCI may likely need bilaterally-synchronized hardware.

Identification of speech sounds is influenced by spectral contrast effects (SCEs), the perceptual magnification of spectral differences between successive sounds. SCEs result in the categorization of a target sound being biased away from spectral properties in the preceding acoustic context. Given remarkable consistency in the magnitudes of these contrast effects within the same frequency region [Stilp (2019) J. Acoust. Soc. Am. 146(2), 1503–1517], it was hypothesized that they would also show stable relationships across different frequency regions. In this study, normal-hearing listeners' phoneme categorization and contrast effects were assessed where phonetic contrasts were driven by changes in low-frequency F1 (“big”-“beg” continuum), mid-frequency F3 (“dot”-“got”), or high-frequency frication spectrum regions (“sheet”-“seat”). On each trial, listeners heard a precursor sentence that was filtered to emphasize energy in the lower or higher range within one of these frequency regions, followed by a target word that hinged on the frequency region that was filtered. Results showed that SCEs influenced categorization in each frequency region, as expected. However, effect magnitudes were not correlated with each other across frequency regions within or across two participant samples. This clarifies perception-in-context on a broader scale as the influence of spectral contrast is independent across different frequency regions.

It is widely known that users of cochlear implants (CIs) often show deficits in binaural hearing. In particular, interaural time difference (ITD) discrimination tends to be substantially worse in CI users. However, only very few studies have investigated how CI stimulation affects the “precedence effect” (PE), and how this might be affected by abnormal hearing experience during development. We performed behavioral experiments to measure temporal weighting functions (TWFs) to quantify the PE in three different cohorts of rats: normally hearing (NH) acoustically stimulated, neonatally deafened (ND) CI-stimulated, and adult deafened (AD) CI-stimulated animals. Lateralization responses were recorded to bursts of eight stimulus pulses in which the ITD of each pulse varied independently, and probit analysis revealed the perceptual weight of each pulse. The NH and ND-CI cohorts were tested at 50, 300, and 900 pps; the AD-CI animals were tested only at 300 pps. The NH animals show a pronounced “onset dominance” at higher pulse rates, that is, the weighting of the first pulse was much larger than for subsequent pulses, exactly as one would expect given previous studies on human listeners. In contrast, the TWFs for the ND-CI and AD-CI animals were much flatter, with a reduction of onset dominance by ∼75%, especially for higher pulse rates. Since neither of our CI cohorts had any experience of reverberation in their electric hearing, we interpret these results to indicate that the PE may require domain-specific experience to develop.

Stories, Chirps, And Noisy Sentences (MEG-SCANS) is a dataset that provides raw magnetoencephalography (MEG) recordings from 24 German-speaking subjects. Each subject listened to approximately one hour of stimuli, including two audiobooks, sentences from the Oldenburger Matrix Sentence Test (OLSA) for Speech Reception Threshold (SRT) assessment, and short up-chirps used to assess MEG signal quality. The dataset includes MEG data, structural MRI (Magnetic Resonance Imaging) scans of the head, corresponding audio material (audiobooks, OLSA envelopes, and chirp stimuli), and behavioral audiogram and SRT results from hearing screenings. Organized according to the Brain Imaging Data Structure (BIDS), this resource offers a robust benchmark for large-scale encoding/decoding analyses of temporally-resolved brain responses to speech. Comprehensive Matlab and Python code are included to replicate key data validations, ensuring transparency and reproducibility.

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.

Purpose Measures of the human medial olivocochlear reflex (MOCR) typically rely on long duration (> 100 ms) or continuously presented broadband elicitors. MOCR gain reduction measured by otoacoustic emissions (OAE) exhibits multiple time constants, including in the hundreds of milliseconds, when elicited by broadband noise. Psychoacoustic studies of gain reduction have largely adopted these elicitor characteristics, but less is known about how broadband elicitor duration affects auditory perception. Additionally, the literature on the relationship between psychoacoustic and OAE measures of gain reduction has yielded mixed results, which is counterintuitive if both measures reflect the same mechanism. In this study, the effects of ipsilateral broadband elicitor duration were evaluated using forward masking psychoacoustic and transient-evoked OAE (TEOAE) paradigms in individuals with normal hearing (N = 19; m = 7, f = 12). Methods Ipsilateral pink broadband noise was used as the elicitor in both experiments, presented at 50 dB SPL (50–800 ms) for the psychoacoustic measures and 50 dB FPL (50–400 ms) for the TEOAE measures. Gain reduction was quantified as the change in signal threshold (2 kHz) and the change in TEOAE level (1/3rd-octave band centered at 2 kHz) with and without the presence of the elicitor. Results The average time constants for psychoacoustic and TEOAE gain reduction were similarly short (< 100 ms), with near-maximal effects observed for elicitor durations of 200 ms. However, individual comparisons of TEOAE and psychoacoustic gain reduction revealed mixed results. Potential factors contributing to this discrepancy are discussed. Conclusion The human MOCR reduces cochlear gain on relatively short time scales (< 100 ms) with ipsilateral broadband elicitors.

Noise-induced hearing loss (NIHL) is a primary contributor to tinnitus, involving mechanisms such as inflammatory damage, central sensitization, and auditory cortex remodeling. However, not all cases of tinnitus are accompanied by NIHL, and the precise relationship between the two remains incompletely understood. Phosphorylation/dephosphorylation, as a core mechanism for fine cellular regulation, influences neuronal excitability, immune responses, and disease development by modulating protein activity, signal transduction, and gene expression. We hypothesized that aberrant phosphorylation levels may alter auditory cortex neuron function, leading to pathological changes at the protein level. Leveraging auditory cortex tissue from a noise-induced tinnitus model, we systematically investigated the pathogenesis of tinnitus and its distinction from NIHL through integrated proteomic and phosphoproteomic analyses. Compared to animals with NIHL alone, the tinnitus model exhibited enhanced neuronal excitability, synaptic dysfunction, hyperactive energy metabolism, and weakened neuroprotection, with disordered membrane receptor function playing a critical role. Multi-omics analysis further revealed that tinnitus development primarily depends on phosphorylation-mediated post-translational modifications reshaping cellular function, rather than changes in protein abundance caused by alterations in gene transcription levels. Collectively, this study elucidates the physiological and cellular structural alterations in noise-induced tinnitus from the dimensions of protein expression and phosphorylation modification. It confirms that tinnitus leads to neural dysfunction through abnormal membrane receptor activity, and the characteristic proteins and phosphorylation sites identified offer novel therapeutic targets for modulating central hyperexcitability in tinnitus.