Cochlear implants (CIs) stimulate auditory neurons with electric pulse trains whose amplitudes are modulated using envelopes extracted from different frequency bands, conveying essential speech cues. This study investigated how the rate of stimulation pulses affects envelope processing and speech perception in ten post-lingually deaf CI users. Amplitude modulation (AM) detection and consonant identification were examined using acoustic stimuli processed by multi-channel and single-channel strategies, with pulse rates ranging from 125 to 2000 pulses per second (pps) for multi-channel stimulation and from 125 to 4000pps for single-channel stimulation. The single-channel conditions encoded the overall broad-band speech envelope by a single electrode and were used to isolate within-electrode temporal modulation coding. For AM detection, the modulation frequency was 25 Hz ensuring sufficient modulation sampling across all carrier rates tested. Even at 125pps, the 25-Hz modulation was represented by five pulses per modulation cycle. Results revealed a significant decline in both AM detection and consonant identification at 125pps, suggesting that poorer speech recognition at low rates may be partly attributable to limitations in temporal modulation processing rather than solely to a restricted range of representable envelope frequencies. Consonant recognition performance remained stable across clinically relevant pulse rates (250-2000pps), though significant listener- and feature-specific effects were observed. Notably, while AM detection and consonant recognition were not significantly correlated within this small cohort, significant correlations were found between single-channel and multi-channel performance in both tasks. These findings support an important role for within-electrode temporal coding in CI speech perception and highlight the clinical relevance of individual variability in pulse rate effects.

Listeners with clinically normal audiograms can still experience difficulty hearing in noise, a problem often discussed in the context of "hidden hearing loss". Cochlear synaptopathy has been proposed as one potential mechanism underlying these deficits, but reliable physiological assays for detecting synaptopathy remain challenging. The present study examined the effects of noise exposure that produced temporary threshold shift (TTS) in chinchillas using cochlear histology, noninvasive physiological measures, and single-unit auditory-nerve recordings. Histology confirmed persistent loss of inner-hair-cell synapses following exposure. ABR thresholds recovered and DPOAE levels were preserved 2 weeks after exposure, and many auditory-nerve response properties, including tuning and rate-level response metrics, showed no significant post-exposure differences among surviving fibers. However, several suprathreshold and timing-related abnormalities persisted after exposure. Suprathreshold ABR measures showed reduced Peak 1 amplitudes and prolonged Peak 5-Peak 1 latencies, while single-unit recordings revealed a reduced proportion of low-SR fibers in the exposed population. Selective post-exposure differences were also observed in auditory-nerve timing and modulation-related metrics, including reduced first-spike timing variability, increased adapted firing rate, reduced envelope-coding strength, and prolonged envelope-coding delay, suggesting residual disruption of suprathreshold temporal coding that may be perceptually relevant for listening in noise. These findings suggest that recovered TTS produces subtle but persistent neural changes that are not fully captured by conventional threshold-based measures. The results may help explain why diagnosis of cochlear synaptopathy remains challenging, and support the use of suprathreshold, latency-sensitive, and modulation-based physiological assays to detect residual neural effects of cochlear synaptopathy.

Tinnitus is commonly associated with maladaptive neural plasticity following hearing loss. Although large language models (LLMs) share similarities with the human brain in language processing and representation, their potential for modeling tinnitus-related neural mechanisms remains limited. This study aimed to develop an LLM-based framework to investigate tinnitus-related maladaptive neural plasticity. An LLM was partitioned into eight independently trainable regions. An exploratory computational analogy of deafferentation-related changes associated with peripheral hearing loss was developed by applying token-specific high-frequency attenuation during training on a commonsense reasoning task. Region-specific contributions to tinnitus-like excess activity were quantified using region-wise plasticity ablation, selectively disabling plasticity in one region at a time. Representational relationships among regions were evaluated using centered kernel alignment. The computational deafferentation analog largely preserved task accuracy but showed increased activity. Region 1 was the only region with a net suppressive contribution to excess activity, whereas region 2 exhibited the largest positive contribution; regions 6 and 8 also contributed positively. Regions 1 and 2 remained representationally distinct across all conditions. Deafferentation tended to reduce region 1-region 2 similarity, whereas plasticity ablation in most regions, except for regions 6 and 8, tended to increase it. The proposed LLM-based framework captured network-level functional dissociations consistent with current theories of hearing loss-associated tinnitus, identifying distinct suppressive, transformation, and higher-order modulatory roles. These findings highlight the potential of LLMs to investigate maladaptive neural changes underlying tinnitus. This framework may provide the foundation for constructing patient-specific digital twins.

The vestibulo-ocular reflex (VOR), which stabilizes gaze during head movement, serves as a key indicator of vestibular integrity. Conventional systems for VOR measurement in mice often require invasive head fixation, posing risks to animal welfare and experimental reproducibility. In this study, we developed and validated a noninvasive immobilization setup for detecting the presence of VOR responses in a severe vestibular impairment mouse model, offering a welfare-oriented alternative to surgically fixed systems. Using video-oculography (VOG), we assessed VOR responses in control and vestibular-impaired CD-1 mice, with vestibular dysfunction induced via oral administration of the ototoxic compound allylnitrile. As expected, allylnitrile-treated mice exhibited a near-complete absence of VOR responses, confirming profound vestibular impairment. Complementary assessments included Vestibular Dysfunction Index (VDI) scoring, swimming tests, immunofluorescent staining for hair cell counts in vestibular cristae and hearing tests. Because the induced, severe deficits precluded quantitative gain and phase analysis in this study, the set-up is currently limited to binary VOR detection in this model. However, further research will determine if under conditions of partial or progressive impairment, this noninvasive system supports more detailed characterization of VOR dynamics. Overall, the optimized, surgery-free setup demonstrated here enhances the reproducibility and welfare standards of vestibular testing in mice, offering a refined platform for detecting VOR presence in a severe vestibular impairment mouse model.

Cochlear implant (CI) candidates with residual low-frequency hearing increasingly receive hearing-preserving electrode arrays to enable electric-acoustic stimulation (EAS). However, assessing very low-frequency hearing in newborns and young children remains difficult. Previous work has shown that acoustic stimulation can mask electrically evoked auditory percepts when stimulation sites are spatially separated. Whether such masking also occurs when electric stimulation is delivered near the round window (RW), prior to cochlear insertion, remains unclear. This study investigated ipsilateral acoustic masking of electric stimulation delivered at apical, basal, and near-RW sites in 12 EAS users with residual low-frequency hearing implanted with short or partially inserted electrode arrays. Using a psychophysical paradigm, threshold elevations of electric pulse trains were measured during simultaneous acoustic stimulation. Electric stimulation was applied at extra-cochlear RW locations and intra-cochlear basal and apical electrodes, while stimulation parameters were systematically varied. With Individually optimized parameters, electric stimulation near the RW reliably evoked auditory percepts without side effects in 8 of 12 participants, though optimal stimulation parameters and masking strength varied across participants. Strong acoustic masking was consistently observed for apical stimulation, whereas weaker but measurable masking occurred for basal and RW stimulation. A cochlear lumped-parameter model indicated that approximately 5% of current delivered at the RW can reach apical regions, explaining the observed masking by low-frequency acoustic tones. Masking strength correlated with residual hearing for apical stimulation only. These findings indicate that acoustic masking of apical electric stimulation, which correlated with residual hearing, holds potential as a diagnostic tool for assessing low-frequency hearing post-operatively. The detection of masking during both RW and basal stimulation represents a promising result, indicating that these stimulation paradigms can produce quantifiable effects. Given the considerable variability observed among participants, further investigation is required to establish the extent to which masking measures reflect residual hearing or hearing loss. Nonetheless, these results provide novel insight into auditory perception and side effects associated with basal and extra-cochlear electric stimulation, informing future efforts to optimize this approach for low-frequency hearing assessment.

This review summarizes our current understanding of the amygdala. As an important part of the limbic system, the amygdala is highly sensitive to environmental stimuli such as sounds. Although the responses of amygdala neurons to sounds are usually not as robust as those of neurons in the primary auditory cortex, the lowest response thresholds of these neurons are consistent with the behavioral audiogram. When a threat is detected through sensory information processing, it immediately triggers a fight-or-flight response, such as freezing and heart rate increase. By learning and remembering environmental events (especially those that may cause harm) and its effects on various instinctive behaviors (such as sexual impulse and maternal behaviors) as well as emotional expressions (such as fear and aggression), it plays a crucial role in the survival and continuation of the species. The response of amygdala neurons to environmental sounds is often composed of an early sharp response component and a late slow response component. The early response is responsible for rapid processing of meaningful information (such as the presence of danger), while the late response can be related to emotional processing. Indeed, the early response of the amygdala is enhanced when there are predator cues or during fear conditioning. Sounds with different emotional tones can trigger different response patterns in the amygdala. It is well documented that the amygdala plays a crucial role in Pavlovian fear conditioning. During this process, both the conditioned stimulus (CS) and the unconditioned stimulus (US) converge on the neurons in the lateral amygdala (LA), thereby activating the central amygdala (CeA) and triggering the conditioned response. Interestingly, the amygdala can be associated with various psychiatric disorders, such as anxiety disorders, depression, and even tinnitus. The amygdala is composed of the LA, the basal lateral amygdala (BLA), the basal medial amygdala (BMA), the CeA, the medial amygdala (MeA) and the cortical amygdala (CoA). The lateral amygdala complex (LA, BLA and BMA) is mainly composed of glutamatergic pyramidal neurons (PNs, accounting for 70%-85% of the total neurons), while the CeA mainly contains GABAergic neurons (>90% of the neurons). Glutamate and GABA are the two main neurotransmitters in the amygdala. In addition, the neural activity of the amygdala can also be regulated by various neurotransmitters, neuromodulators and hormones from other areas of the brain, such as acetylcholine (ACh), dopamine (DA), serotonin (5-HT), norepinephrine (NE), and glucocorticoids. The LA receives sensory information from both the thalamus (the fast low road) and the cortex (the slow high road). The PNs in the LA can directly stimulate the projection neurons in the CeA, thereby triggering corresponding behavioral responses, such as urgent response or fear conditioning. The LA PNs can also project to the BLA and BMA for further information processing. The PNs in the BLA/BMA can directly project to the CeA or project to the hippocampus and the prefrontal cortex for processing. The rapid fear conditioning can be achieved through the fast low road. However, the information processing results through the slow high road may modulate or override the initial fear response through the fast low road. More than 90% of the neurons in the CeA are inhibitory neurons, inhibiting neural activity of the brainstem. For example, in the context of freezing behavior, they can inhibit the neural activity of the pre-Bötzinger complex, thereby suppressing breathing. The CeA also contains excitatory neurons (<10%). They can excite neurons in the hypothalamus or in the caudal pontine reticular nucleus, triggering the fight-or-flight response or leading to an enhanced auditory startle response.

The rat superior paraolivary nucleus (SPON) is a prominent cell group in the superior olivary complex (SOC). The SOC functions in several aspects of hearing, including sound source localization, coding spectral and temporal features of sounds and descending modulation of the cochlea. Neurons in the rat SPON appear to function mainly in coding sound offsets through GABAergic projections to the midbrain and thalamus. SPON neurons have multipolar dendritic arbors, and several qualitative studies have identified dendritic branches extending beyond the nucleus and into the nearby ventral nucleus of the trapezoid body (VNTB). The purpose of this study was to gauge the predominance of SPON dendrites extending into the VNTB, determine if other SOC nuclei receive such dendrites and perform a quantitative analysis of SPON dendritic arbors. A combination of immunohistochemistry and Golgi impregnations revealed that rat SPON neurons send dendrites in all directions, and the majority of neurons have dendrites that extend into the VNTB and frequently into the dorsal ribbon of the SOC (dSOC). Additionally, there were regional differences in SPON dendrites, including orientation angle, arbor shape and which SOC nuclei were reached, which may impact response properties and dynamic range. The function of SPON dendrites extending into adjacent nuclei is unclear but may involve sampling of descending input from the inferior colliculus and auditory cortex.

Age-related hearing loss reflects a mixture of concurrent peripheral cochlear and central auditory pathway degeneration. Disentangling their relative contributions has remained challenging because both decline together with natural aging. Here, we test the hypothesis that systemic D-galactose (D-gal) administration will selectively accelerate central auditory aging while preserving peripheral cochlear function. Eight male Fischer 344 rats received daily subcutaneous D-gal injections (500 mg/kg) for eight consecutive weeks. Two-channel auditory evoked potentials, including auditory brainstem responses (ABRs) and envelope-following responses (EFRs), were recorded at three time points: pre-injection, immediately following injections (2 months post), and 12 months post-injection cessation. Two months post-injection, there was a significant reduction in ABR wave amplitudes from central auditory generators (Waves IV and V) and EFRs to slow modulation frequencies (≤45 Hz), which reflect midbrain and cortical generators. In contrast, ABR thresholds, wave amplitudes from peripheral generators (Waves I and III), and EFRs to fast modulation rates (>128 Hz), reflecting peripheral neural activity, remained unchanged at this time point, indicating preserved cochlear and early brainstem function. Peripheral deficits emerged only by the 12-month follow-up, with elevated thresholds, reduced peripheral wave amplitudes, and reduced EFRs at fast modulation rates, consistent with presbycusis. These findings demonstrate a clear temporal dissociation in which central auditory decline in the D-gal model precedes age-related peripheral cochlear and neural loss. This paradigm provides a tractable experimental window for studying mechanisms of central auditory aging in isolation from age-related cochlear pathology, bridging an important gap between peripheral and central models of presbycusis.

Hyperacusis is an excessive, sometimes painful response to sounds of moderate volume. In the past 25 years, attempts have been made to assess it via questionnaires in addition to audiological measures. In the present study, two recently developed self-report questionnaires [Aazh, et al., 2022, J Am Acad Audiol 33(5), 248-258] designed to assess the presence and severity of hyperacusis were investigated in an online survey, namely the 8-item Hyperacusis Impact Questionnaire (HIQ), and the 5-item Sound Sensitivity Symptoms Questionnaire (SSSQ). The non-clinical sample, stratified by age and sex, consisted of N = 213 participants from Germany and Austria of whom N = 187 participated in a retest. As a result, the German-language versions of both questionnaires closely replicated the psychometric properties (distributions, factor structure, and internal consistency) of the original. Compared to the normally distributed scores obtained in the same sample with Weinstein's noise sensitivity questionnaire, the total-score distributions of the hyperacusis questionnaires were skewed, with a fifth (HIQ) to a third (SSSQ) of the participants showing no (or hardly any) hyperacusis symptoms. Both consequences of hyperacusis (HIQ: Spearman's ρ = .57) and the severity of symptoms (SSSQ: ρ = .42) correlated moderately with noise sensitivity. The apparent differences in total-score distributions, in temporal stability, and in the correlations with noise annoyance further suggest that hyperacusis and noise sensitivity are distinct, though partially overlapping constructs that may be distinguished at the conceptual, measurement, and empirical level.

Bilateral cochlear implantation is a primary clinical intervention to re-establish access to binaural hearing in individuals with severe-to-profound hearing loss. While many binaural auditory functions depend critically on interaural cues, existing sound coding strategies do not fully preserve these cues. Based on simulations, this study systematically examines how cochlear implant signal processing affects the encoding of interaural time and level differences across key processing stages. The impact of linked channel selection and number of maxima is also investigated on binaural cue encoding and speech intelligibility in noise. Non-linear compressions emerge as the dominant source of interaural level distortion, introducing errors up to 10.4 ± 0.5 dB. While envelope extraction and channel selection are the primary contributors to interaural timing degradation, with errors up to 101 ± 17 µs. Linking channel selection between left and right processors reduces level distortions under strong head-shadow conditions (from 1.8 ± 0.2 dB to 0.2 ± 0.1 dB), however, this improvement does not persist at later processing stages and also introduces substantial timing distortions (up to 338 ± 14 µs). Increasing maxima from 8 to 12 provides modest benefits, while further increases lead to little extra improvement, which also does not persist at later processing stages. Speech intelligibility simulation analyses show consistent benefits of linked channel selection on the side with poorer signal-to-noise ratio, also when increasing maxima from 8 to 12 to 16. These findings underscore persistent limitations in interaural cue preservation and highlight the need for coding strategies that explicitly preserve these cues.

The medial olivocochlear efferent system has been proposed to influence the maturation of auditory circuits during early postnatal development. Here, we examined the acquisition of auditory evoked responses in mice with absent α9α10 nicotinic cholinergic receptor activity (α9 knock-out mice; α9KO) or enhanced medial olivocochlear function (α9 knock-in mice; α9KI). Auditory brainstem responses were evaluated throughout juvenile postnatal development. Enhanced medial olivocochlear activity accelerated the onset and early maturation of auditory function, whereas its absence delayed these developmental processes. Despite this accelerated maturation, α9KI mice exhibited reduced auditory brainstem response wave amplitudes later in development, resembling the deficits observed in α9KO mice. Thus, enhanced and absent medial olivocochlear activity produced opposing effects on the timing of auditory maturation but converged on reduced response wave amplitudes later in development. Together, these findings suggest that appropriate levels of medial olivocochlear activity are required for normal maturation of the auditory system.