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• Cochlear implantation is known to enhance compensatory brain plasticity. • We asked whether normal activity patterns are restored after asymmetric hearing loss. • A nearly normal pattern of brain activity during the auditory task was found. • Resting-state activity showed plasticity due to cross modal visuo-auditory processing. Brain plasticity refers to the brain's ability to reorganize its structure or function in response to experiences, learning, and environmental influences. This phenomenon is particularly significant in individuals with deafness, as the brain adapts to compensate for the lack of auditory stimulation. The aim of this study is to investigate whether cochlear implantation can restore a normal pattern of brain activation following auditory stimulation in cases of asymmetric hearing loss. We used a PET-scan technique to assess brain activity after cochlear implantation, specifically during an auditory voice/non-voice discrimination task. The results indicated a nearly normal pattern of brain activity during the auditory discrimination task, except for increased activation in areas related to attentional processes compared to controls. Additionally, brain activity at rest showed significant changes in implanted participants, including cross modal visuo-auditory processing. Therefore, cochlear implants can restore the brain's activation pattern through long-term adaptive adjustments in intrinsic brain activity. [ABSTRACT FROM AUTHOR]

• Wireless EcochG is a feasible way to record high-quality signals reflecting receptor and neural activity from the cochlea. • Spontaneous auditory-nerve activity was modulated by visual crossmodal stimulation. The discovery and development of electrocochleography (ECochG) in animal models has been fundamental for its implementation in clinical audiology and neurotology. In our laboratory, the use of round-window ECochG recordings in chinchillas has allowed a better understanding of auditory efferent functioning. In previous works, we gave evidence of the corticofugal modulation of auditory-nerve and cochlear responses during visual attention and working memory. However, whether these cognitive top-down mechanisms to the most peripheral structures of the auditory pathway are also active during audiovisual crossmodal stimulation is unknown. Here, we introduce a new technique, wireless ECochG to record compound-action potentials of the auditory nerve (CAP), cochlear microphonics (CM), and round-window noise (RWN) in awake chinchillas during a paradigm of crossmodal (visual and auditory) stimulation. We compared ECochG data obtained from four awake chinchillas recorded with a wireless ECochG system with wired ECochG recordings from six anesthetized animals. Although ECochG experiments with the wireless system had a lower signal-to-noise ratio than wired recordings, their quality was sufficient to compare ECochG potentials in awake crossmodal conditions. We found non-significant differences in CAP and CM amplitudes in response to audiovisual stimulation compared to auditory stimulation alone (clicks and tones). On the other hand, spontaneous auditory-nerve activity (RWN) was modulated by visual crossmodal stimulation, suggesting that visual crossmodal simulation can modulate spontaneous but not evoked auditory-nerve activity. However, given the limited sample of 10 animals (4 wireless and 6 wired), these results should be interpreted cautiously. Future experiments are required to substantiate these conclusions. In addition, we introduce the use of wireless ECochG in animal models as a useful tool for translational research. [ABSTRACT FROM AUTHOR]

• Cortical Auditory Evoked Potentials (CAEPs) measured in normal hearing (NH) listeners and bimodal cochlear implant (CI) users. • Time-frequency analysis of CAEPs as a tool to investigate integration. • Interaural temporal mismatch resulted in reduced N1 amplitude and phase locking value in NH listeners. • CAEPs offer a means to estimate cortical delay between electric and acoustic stimulation in bimodal individuals. • Correcting individual temporal interaural mismatch in bimodal CI users led to an increase in N1 amplitude. • Limited phase locking increase suggests constrained electric-acoustic cortical integration. Combining a cochlear implant with contralateral acoustic hearing typically enhances speech understanding, although this improvement varies among CI users and can lead to an interference effect. This variability may be associated with the effectiveness of the integration between electric and acoustic stimulation, which might be affected by the temporal mismatch between the two listening sides. Finding methods to compensate for the temporal mismatch might contribute to the optimal adjustment of bimodal devices and to improve hearing in CI users with contralateral acoustic hearing. The current study investigates cortical auditory evoked potentials (CAEPs) in normal hearing listeners (NH) and CI users with contralateral acoustic hearing. In NH, the amplitude of the N1 peak and the maximum phase locking value (PLV) were analyzed under monaural, binaural, and binaural temporally mismatched conditions. In CI users, CAEPs were measured when listening with CI only (CIS_only), acoustically only (AS_only) and with both sides together (CIS+AS). When listening with CIS+AS, various interaural delays were introduced between the electric and acoustic stimuli. In NH listeners, interaural temporal mismatch resulted in decreased N1 amplitude and PLV. Moreover, PLV is suggested as a more sensitive measure to investigate the integration of information between the two listening sides. CI users showed varied N1 latencies between the AS_only and CIS_only listening conditions, with increased N1 amplitude when the temporal mismatch was compensated. A tendency towards increased PLV was also observed, however, to a lesser extent than in NH listeners, suggesting a limited integration between electric and acoustic stimulation. This work highlights the potential of CAEPs measurement to investigate cortical processing of the information between two listening sides in NH and bimodal CI users. [ABSTRACT FROM AUTHOR]

The genes Ocm (encoding oncomodulin) and Slc26a5 (encoding prestin) are expressed strongly in outer hair cells and both are involved in deafness in mice. However, it is not clear if they influence the expression of each other. In this study, we characterise the auditory phenotype resulting from two new mouse alleles, Ocm tm1e and Slc26a5 tm1Cre . Each mutation leads to absence of detectable mRNA transcribed from the mutant allele, but there was no evidence that oncomodulin regulates expression of prestin or vice versa. The two mutants show distinctive patterns of auditory dysfunction. Ocm tm1e homozygotes have normal auditory brainstem response thresholds at 4 weeks old followed by progressive hearing loss starting at high frequencies, while heterozygotes show largely normal thresholds until 6 months of age, when signs of worse thresholds are detected. In contrast, Slc26a5 tm1Cre homozygotes have stable but raised thresholds across all frequencies tested, 3 to 42 kHz, at least from 4 to 8 weeks old, while heterozygotes have raised thresholds at high frequencies. Distortion product otoacoustic emissions and cochlear microphonics show deficits similar to auditory brainstem responses in both mutants, suggesting that the origin of hearing impairment is in the outer hair cells. Endocochlear potentials are normal in the two mutants. Scanning electron microscopy revealed normal development of hair cells in Ocm tm1e homozygotes but scattered outer hair cell loss even at 4 weeks old when thresholds appeared normal, indicating that there is not a direct relationship between numbers of outer hair cells present and auditory thresholds., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

The detection of novel, low probability events in the environment is critical for survival. To perform this vital task, our brain is continuously building and updating a model of the outside world; an extensively studied phenomenon commonly referred to as predictive coding. Predictive coding posits that the brain is continuously extracting regularities from the environment to generate predictions. These predictions are then used to supress neuronal responses to redundant information, filtering those inputs, which then automatically enhances the remaining, unexpected inputs. We have recently described the ability of auditory neurons to generate predictions about expected sensory inputs by detecting their absence in an oddball paradigm using omitted tones as deviants. Here, we studied the responses of individual neurons to omitted tones by presenting individual sequences of repetitive pure tones, using both random and periodic omissions, presented at both fast and slow rates in the inferior colliculus and auditory cortex neurons of anesthetized rats. Our goal was to determine whether feature-specific dependence of these predictions exists. Results showed that omitted tones could be detected at both high (8 Hz) and slow repetition rates (2 Hz), with detection being more robust at the non-lemniscal auditory pathway., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cochlear implant (CI) users experience diminished music enjoyment due to the technical limitations of the CI. Nonetheless, behavioral studies have reported that rhythmic features are well-transmitted through the CI. Still, the gradual improvement of rhythm perception after the CI switch-on has not yet been determined using neurophysiological measures. To fill this gap, we here reanalyzed the electroencephalographic responses of participants from two previous mismatch negativity studies. These studies included eight recently implanted CI users measured twice, within the first six weeks after CI switch-on and approximately three months later; thirteen experienced CI users with a median experience of 7 years; and fourteen normally hearing (NH) controls. All participants listened to a repetitive four-tone pattern (known in music as Alberti bass) for 35 min. Applying frequency tagging, we aimed to estimate the neural activity synchronized to the periodicities of the Alberti bass. We hypothesized that longer experience with the CI would be reflected in stronger frequency-tagged neural responses approaching the responses of NH controls. We found an increase in the frequency-tagged amplitudes after only 3 months of CI use. This increase in neural synchronization may reflect an early adaptation to the CI stimulation. Moreover, the frequency-tagged amplitudes of experienced CI users were significantly greater than those of recently implanted CI users, but still smaller than those of NH controls. The frequency-tagged neural responses did not just reflect spectrotemporal changes in the stimuli (i.e., intensity or spectral content fluctuating over time), but also showed non-linear transformations that seemed to enhance relevant periodicities of the Alberti bass. Our findings provide neurophysiological evidence indicating a gradual adaptation to the CI, which is noticeable already after three months, resulting in close to NH brain processing of spectrotemporal features of musical rhythms after extended CI use., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Sound localization in the front-back dimension is reported to be challenging, with individual differences. We investigated whether auditory discrimination processing in the brain differs based on front-back sound localization ability. This study conducted an auditory oddball task using speakers in front of and behind the participants. We used event-related brain potentials to examine the deviance detection process between groups that could and could not discriminate front-back sound localization. The results indicated that mismatch negativity (MMN) occurred during the deviance detection process, and P2 amplitude differed between standard and deviant locations in both groups. However, the latency of MMN was shorter in the group that could discriminate front-back sounds than in the group that could not. Additionally, N1 amplitude increased for deviant locations compared to standard ones only in the discriminating group. In conclusion, the sensory memories matching process based on traces of previously presented stimuli (MMN, P2) occurred regardless of discrimination ability. However, the response to changes in the physical properties of sounds (MMN latency, N1 amplitude) differed depending on the ability to discriminate front-back sounds. Our findings suggest that the brain may have different processing strategies for the two directions even without subjective recognition of the front-back direction of incoming sounds., Competing Interests: Declaration of competing interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2024. Published by Elsevier B.V.)

The binaural interaction component (BIC) of the auditory evoked potential is the difference between the waveforms of the binaural response and the sum of left and right monaural responses. This investigation examined BICs of the auditory brainstem (ABR) and middle-latency (MLR) responses concerning three objectives: 1) the level of the auditory system at which low-frequency dominance in BIC amplitudes begins when the binaural temporal fine structure is more influential with lower- than higher-frequency content; 2) how BICs vary as a function of frequency and lateralization predictability, as could relate to the improved lateralization of high-frequency sounds; 3) how attention affects BICs. Sixteen right-handed participants were presented with either low-passed (< 1000 Hz) or high-passed (> 2000 Hz) clicks at 30 dB SL with a 38 dB (A) masking noise, at a stimulus onset asynchrony of 180 ms. Further, this repeated-measures design manipulated stimulus presentation (binaural, left monaural, right monaural), lateralization predictability (unpredictable, predictable), and attended modality (either auditory or visual). For the objectives, respectively, the results were: 1) whereas low-frequency dominance in BIC amplitudes began during, and continued after, the Na-BIC, binaural (center) as well as summed monaural (left and right) amplitudes revealed low-frequency dominance only after the Na wave; 2) with a predictable position that was fixed, no BIC exhibited equivalent amplitudes between low- and high-passed clicks; 3) whether clicks were low- or high-passed, selective attention affected the ABR-BIC yet not MLR-BICs. These findings indicate that low-frequency dominance in lateralization begins at the Na latency, being independent of the efferent cortico-collicular pathway's influence., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Congenital or early-onset unilateral hearing loss (UHL) can disrupt the normal development of the auditory system. In extreme cases of UHL (i.e., single sided deafness), consistent cochlear implant use during sensitive periods resulted in cortical reorganization that partially reversed the detrimental effects of unilateral sensory deprivation. There is a gap in knowledge, however, regarding cortical plasticity i.e. the brain's capacity to adapt, reorganize, and develop binaural pathways in milder degrees of UHL rehabilitated by a hearing aid (HA). The current study was set to investigate early-stage cortical processing and electrophysiological manifestations of binaural processing by means of cortical auditory evoked potentials (CAEPs) to speech sounds, in children with moderate to severe-to-profound UHL using a HA. Fourteen children with UHL (CHwUHL), 6-14 years old consistently using a HA for 3.5 (±2.3) years participated in the study. CAEPs were elicited to the speech sounds /m/, /g/, and /t/ in three listening conditions: monaural [Normal hearing (NH), HA], and bilateral [BI (NH + HA)]. Results indicated age-appropriate CAEP morphology in the NH and BI listening conditions in all children. In the HA listening condition: (1) CAEPs showed similar morphology to that found in the NH listening condition, however, the mature morphology observed in older children in the NH listening condition was not evident; (2) P1 was elicited in all but two children with severe-to-profound hearing loss, to at least one speech stimuli, indicating effective audibility; (3) A significant mismatch in timing and synchrony between the NH and HA ear was found; (4) P1 was sensitive to the acoustic features of the eliciting stimulus and to the amplification characteristics of the HA. Finally, a cortical binaural interaction component (BIC) was derived in most children. In conclusion, the current study provides first-time evidence for cortical plasticity and partial reversal of the detrimental effects of moderate to severe-to-profound UHL rehabilitated by a HA. The derivation of a cortical biomarker of binaural processing implies that functional binaural pathways can develop when sufficient auditory input is provided to the affected ear. CAEPs may thus serve as a clinical tool for assessing, monitoring, and managing CHwUHL using a HA., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Musicians are at risk of hearing loss and tinnitus due to regular exposure to high levels of noise. This level of risk may have been underestimated previously since damage to the auditory system, such as cochlear synaptopathy, may not be easily detectable using standard clinical measures. Most previous research investigating hearing loss in musicians has involved cross-sectional study designs that may capture only a snapshot of hearing health in relation to noise exposure. The aim of this study was to investigate the effects of cumulative noise exposure on behavioural, electrophysiological, and self-report indices of hearing damage in early-career musicians and non-musicians with normal hearing over a 2-year period. Participants completed an annual test battery consisting of pure tone audiometry, extended high-frequency hearing thresholds, distortion product otoacoustic emissions (DPOAEs), speech perception in noise, auditory brainstem responses, and self-report measures of tinnitus, hyperacusis, and hearing in background noise. Participants also completed the Noise Exposure Structured Interview to estimate cumulative noise exposure across the study period. Linear mixed models assessed changes over time. The longitudinal analysis comprised 64 early-career musicians (female n = 34; age range at T0 = 18-26 years) and 30 non-musicians (female n = 20; age range at T0 = 18-27 years). There were few longitudinal changes as a result of musicianship. Small improvements over time in some measures may be attributable to a practice/test-retest effect. Some measures (e.g., DPOAE indices of outer hair cell function) were associated with noise exposure at each time point, but did not show a significant change over time. A small proportion of participants reported a worsening of their tinnitus symptoms, which participants attributed to noise exposure, or not using hearing protection. Future longitudinal studies should attempt to capture the effects of noise exposure over a longer period, taken at several time points, for a precise measure of how hearing changes over time. Hearing conservation programmes for "at risk" individuals should closely monitor DPOAEs to detect early signs of noise-induced hearing loss when audiometric thresholds are clinically normal., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Speech-in-noise (SIN) perception is a fundamental ability that declines with aging, as does general cognition. We assess whether auditory cognitive ability, in particular short-term memory for sound features, contributes to both. We examined how auditory memory for fundamental sound features, the carrier frequency and amplitude modulation rate of modulated white noise, contributes to SIN perception. We assessed SIN in 153 healthy participants with varying degrees of hearing loss using measures that require single-digit perception (the Digits-in-Noise, DIN) and sentence perception (Speech-in-Babble, SIB). Independent variables were auditory memory and a range of other factors including the Pure Tone Audiogram (PTA), a measure of dichotic pitch-in-noise perception (Huggins pitch), and demographic variables including age and sex. Multiple linear regression models were compared using Bayesian Model Comparison. The best predictor model for DIN included PTA and Huggins pitch (r 2 = 0.32, p < 0.001), whereas the model for SIB included the addition of auditory memory for sound features (r 2 = 0.24, p < 0.001). Further analysis demonstrated that auditory memory also explained a significant portion of the variance (28 %) in scores for a screening cognitive test for dementia. Auditory memory for non-speech sounds may therefore provide an important predictor of both SIN and cognitive ability., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Musicians perform better than non-musicians on a variety of non-musical sound-perception tasks. Whether that musicians' advantage extends to spatial hearing is a topic of increasing interest. Here we investigated one facet of that topic by assessing musicians' and non-musicians' sensitivity to the two primary cues to sound-source location on the horizontal plane: interaural-level-differences (ILDs) and interaural-time-differences (ITDs). Specifically, we measured discrimination thresholds for ILDs at 4 kHz (n =246) and ITDs at 0.5 kHz (n = 137) in participants whose musical-training histories covered a wide range of lengths, onsets, and offsets. For ILD discrimination, when only musical-training length was considered in the analysis, no musicians' advantage was apparent. However, when thresholds were compared between subgroups of non-musicians (<2 years of training) and extreme musicians (≥10 years of training, started ≤ age 7, still playing) a musicians' advantage emerged. Threshold comparisons between the extreme musicians and other subgroups of highly trained musicians (≥10 years of training) further indicated that the advantage required both starting young and continuing to play. In addition, the advantage was larger in males than in females, by some measures, and was not evident in an assessment of learning. For ITD discrimination, in contrast to ILD discrimination, parallel analyses revealed no apparent musicians' advantage. The results suggest that musicianship is associated with greater sensitivity to ILDs, a fundamental sound-localization cue, even though that sensitivity is not central to music, that this musicians' advantage arises, at least in part, from nurture, and that it is governed by a neural substrate where ILDs are processed separately from, and more malleably than, ITDs., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The acoustic change complex (ACC) is a cortical auditory evoked potential (CAEP) and can be elicited by a change in an otherwise continuous sound. The ACC has been highlighted as a promising tool in the assessment of sound and speech discrimination capacity, and particularly for difficult-to-test populations such as infants with hearing loss, due to the objective nature of ACC measurements. Indeed, there is a pressing need to develop further means to accurately and thoroughly establish the hearing status of children with hearing loss, to help guide hearing interventions in a timely manner. Despite the potential of the ACC method, ACC measurements remain relatively rare in a standard clinical settings. The objective of this study was to perform an up-to-date systematic review on ACC measurements in children, to provide greater clarity and consensus on the possible methodologies, applications, and performance of this technique, and to facilitate its uptake in relevant clinical settings., Design: Original peer-reviewed articles conducting ACC measurements in children (< 18 years). Data were extracted and summarised for: (1) participant characteristics; (2) ACC methods and auditory stimuli; (3) information related to the performance of the ACC technique; (4) ACC measurement outcomes, advantages, and challenges. The systematic review was conducted using PRISMA guidelines for reporting and the methodological quality of included articles was assessed., Results: A total of 28 studies were identified (9 infant studies). Review results show that ACC responses can be measured in infants (from < 3 months), and there is evidence of age-dependency, including increased robustness of the ACC response with increasing childhood age. Clinical applications include the measurement of the neural capacity for speech and non-speech sound discrimination in children with hearing loss, auditory neuropathy spectrum disorder (ANSD) and central auditory processing disorder (CAPD). Additionally, ACCs can be recorded in children with hearing aids, auditory brainstem implants, and cochlear implants, and ACC results may guide hearing intervention/rehabilitation strategies. The review identified that the time taken to perform ACC measurements was often lengthy; the development of more efficient ACC test procedures for children would be beneficial. Comparisons between objective ACC measurements and behavioural measures of sound discrimination showed significant correlations for some, but not all, included studies., Conclusions: ACC measurements of the neural capacity to discriminate between speech and non-speech sounds are feasible in infants and children, and a wide range of possible clinical applications exist, although more time-efficient procedures would be advantageous for clinical uptake. A consideration of age and maturational effects is recommended, and further research is required to investigate the relationship between objective ACC measures and behavioural measures of sound and speech perception for effective clinical implementation., Competing Interests: Declaration of competing interest None (the authors have no financial disclosures or competing interests to disclose)., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Auditory masking methods originally employed to assess behavioral frequency selectivity have evolved over the years to infer cochlear tuning. Behavioral forward masking thresholds for spectrally notched noise maskers and a fixed, low-level probe tone provide accurate estimates of cochlear tuning. Here, we use this method to investigate the effect of stimulus duration on human cochlear tuning at 500 Hz and 4 kHz. Probes were 20-ms sinusoids at 10 dB sensation level. Maskers were noises with a spectral notch symmetrically and asymmetrically placed around the probe frequency. For seven participants with normal hearing, masker levels at masking threshold were measured in forward masking for various notch widths and for masker durations of 30 and 400 ms. Measurements were fitted assuming rounded exponential filter shapes and the power spectrum model of masking, and equivalent rectangular bandwidths (ERBs) were inferred from the fits. At 4 kHz, masker thresholds were higher for the shorter maskers but ERBs were not significantly different for the two masker durations (ERB 30ms =294 Hz vs. ERB 400ms =277 Hz). At 500 Hz, by contrast, notched-noise curves were shallower for the 30-ms than the 400-ms masker, and ERBs were significantly broader for the shorter masker (ERB 30ms =126 Hz vs. ERB 400ms =55 Hz). We discuss possible factors that may underlay the duration effect at low frequencies and argue that it may not be possible to fully control for those factors. We conclude that tuning estimates are not affected by maker duration at high frequencies but should be measured and interpreted with caution at low frequencies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The current study investigated the effect of lower frequency input on stream segregation acuity in older, normal hearing adults. Using event-related brain potentials (ERPs) and perceptual performance measures, we previously showed that stream segregation abilities were less proficient in older compared to younger adults. However, in that study we used frequency ranges greater than 1500 Hz. In the current study, we lowered the target frequency range below 1500 Hz and found similar stream segregation abilities in younger and older adults. These results indicate that the perception of complex auditory scenes is influenced by the spectral content of the auditory input and suggest that lower frequency ranges of input in older adults may facilitate listening ability in complex auditory environments. These results also have implications for the advancement of prosthetic devices., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier B.V.)

Tinnitus denotes the perception of a non-environmental sound and might result from aberrant auditory prediction. Successful prediction of formal (e.g., type) and temporal sound characteristics facilitates the filtering of irrelevant information, also labelled as 'sensory gating' (SG). Here, we explored if and how parallel manipulations of formal prediction violations and temporal predictability affect SG in persons with and without tinnitus. Age-, education- and sex-matched persons with and without tinnitus (N = 52) participated and listened to paired-tone oddball sequences, varying in formal (standard vs. deviant pitch) and temporal predictability (isochronous vs. random timing). EEG was recorded from 128 channels and data were analyzed by means of temporal spatial principal component analysis (tsPCA). SG was assessed by amplitude suppression for the 2nd tone in a pair and was observed in P50-like activity in both timing conditions and groups. Correspondingly, deviants elicited overall larger amplitudes than standards. However, only persons without tinnitus displayed a larger N100-like deviance response in the isochronous compared to the random timing condition. This result might imply that persons with tinnitus do not benefit similarly as persons without tinnitus from temporal predictability in deviance processing. Thus, persons with tinnitus might display less temporal sensitivity in auditory processing than persons without tinnitus., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

The study aimed to explore the auditory temporal resolution and dichotic listening skills in patients with type 2 diabetes mellitus (T2DM) and identify associated health-related factors. Using a cross-sectional design, 87 adults with T2DM and 48 non-diabetic controls, all with normal hearing, participated. The two central auditory processing (CAP) skills were assessed through the Gaps-In-Noise (GIN) and Dichotic-Digits Listening (DDL) tests. T2DM participants underwent blood tests to measure various health-related factors. In the GIN test, the shortest gap threshold (GapTh) obtained across both ears was significantly higher in the diabetic group (9.1 ± 2.4 ms) compared to the non-diabetic group (7.5 ± 1.5 ms), and the score of correctly identified gaps (GapSc) in the diabetic group (45±11 %) was significantly lower than GapSc in the non-diabetic group (52±9 %), p < 0.001. In the DDL test, the free-recall score (73.8 ± 18.5 %) across both ears and the right-ear advantage (-1.3 ± 20.6 %) in the diabetic group were significantly lower than the free-recall score (85.8 ± 11.9 %) and right-ear advantage (6.9 ± 11.9 %) in the non-diabetic group, p < 0.005. Furthermore, the duration of diabetes, eGFR level, retinopathy, carotid plaque, fasting blood glucose level, and HDL-C (good cholesterol) level were factors significantly associated with performances in the GIN and/or DDL tests for T2DM participants. In conclusion, individuals with T2DM are at risk of reduced auditory processing skills in temporal resolution and dichotic listening, impacting their speech understanding. Six health-related factors were identified as significantly associated with CAP skills in T2DM patients., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Contemporary cochlear implants (CIs) use cathodic-leading symmetric biphasic (C-BP) pulses for electrical stimulation. It remains unclear whether asymmetric pulses emphasizing the anodic or cathodic phase may improve spectral and temporal coding with CIs. This study tested place- and temporal-pitch sensitivity with C-BP, anodic-centered triphasic (A-TP), and cathodic-centered triphasic (C-TP) pulse trains on apical, middle, and basal electrodes in 10 implanted ears. Virtual channel ranking (VCR) thresholds (for place-pitch sensitivity) were measured at both a low and a high pulse rate of 99 (Experiment 1) and 1000 (Experiment 2) pulses per second (pps), and amplitude modulation frequency ranking (AMFR) thresholds (for temporal-pitch sensitivity) were measured at a 1000-pps pulse rate in Experiment 3. All stimuli were presented in monopolar mode. Results of all experiments showed that detection thresholds, most comfortable levels (MCLs), VCR thresholds, and AMFR thresholds were higher on more basal electrodes. C-BP pulses had longer active phase duration and thus lower detection thresholds and MCLs than A-TP and C-TP pulses. Compared to C-TP pulses, A-TP pulses had lower detection thresholds at the 99-pps but not the 1000-pps pulse rate, and had lower MCLs at both pulse rates. A-TP pulses led to lower VCR thresholds than C-BP pulses, and in turn than C-TP pulses, at the 1000-pps pulse rate. However, pulse shape did not affect VCR thresholds at the 99-pps pulse rate (possibly due to the fixed temporal pitch) or AMFR thresholds at the 1000-pps pulse rate (where the overall high performance may have reduced the changes with different pulse shapes). Notably, stronger polarity effect on VCR thresholds (or more improvement in VCR with A-TP than with C-TP pulses) at the 1000-pps pulse rate was associated with stronger polarity effect on detection thresholds at the 99-pps pulse rate (consistent with more degeneration of auditory nerve peripheral processes). The results suggest that A-TP pulses may improve place-pitch sensitivity or spectral coding for CI users, especially in situations with peripheral process degeneration., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Following adult-onset hearing impairment, crossmodal plasticity can occur within various sensory cortices, often characterized by increased neural responses to visual stimulation in not only the auditory cortex, but also in the visual and audiovisual cortices. In the present study, we used an established model of loud noise exposure in rats to examine, for the first time, whether the crossmodal plasticity in the audiovisual cortex that occurs following a relatively mild degree of hearing loss emerges solely from altered intracortical processing or if thalamocortical changes also contribute to the crossmodal effects. Using a combination of an established pharmacological 'cortical silencing' protocol and current source density analysis of the laminar activity recorded across the layers of the audiovisual cortex (i.e., the lateral extrastriate visual cortex, V2L), we observed layer-specific changes post-silencing in the strength of the residual visual, but not auditory, input in the noise exposed rats with mild hearing loss compared to rats with normal hearing. Furthermore, based on a comparison of the laminar profiles pre- versus post-silencing in both groups, we can conclude that noise exposure caused a re-allocation of the strength of visual inputs across the layers of the V2L cortex, including enhanced visual-evoked activity in the granular layer; findings consistent with thalamocortical plasticity. Finally, we confirmed that audiovisual integration within the V2L cortex depends on intact processing within intracortical circuits, and that this form of multisensory processing is vulnerable to disruption by noise-induced hearing loss. Ultimately, the present study furthers our understanding of the contribution of intracortical and thalamocortical processing to crossmodal plasticity as well as to audiovisual integration under both normal and mildly-impaired hearing conditions., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background & Rationale: In prior work using non-speech stimuli, children with hearing loss show impaired perception of binaural cues and no significant change in cortical responses to bilateral versus unilateral stimulation. Aims of the present study were to: 1) identify bilateral responses to envelope and spectral components of a speech syllable using the frequency-following response (FFR), 2) determine if abnormalities in the bilateral FFR occur in children with hearing loss, and 3) assess functional consequences of abnormal bilateral FFR responses on perception of binaural timing cues., Methods: A single-syllable speech stimulus (/dα/) was presented to each ear individually and bilaterally. Participants were 9 children with normal hearing (M Age = 12.1 ± 2.5 years) and 6 children with bilateral hearing loss who were experienced bilateral hearing aid users (M Age = 14.0 ± 2.6 years). FFR temporal and spectral peak amplitudes were compared between listening conditions and groups using linear mixed model regression analyses. Behavioral sensitivity to binaural cues were measured by lateralization responses as coming from the right or left side of the head., Results: Both temporal and spectral peaks in FFR responses increased in amplitude in the bilateral compared to unilateral listening conditions in children with normal hearing. These measures of "bilateral advantage" were reduced in the group of children with bilateral hearing loss and associated with decreased sensitivity to interaural timing differences., Conclusion: This study is the first to show that bilateral responses in both temporal and spectral domains can be measured in children using the FFR and is altered in children with hearing loss with consequences to binaural hearing., (Copyright © 2024. Published by Elsevier B.V.)

Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways., Competing Interests: Declaration of competing interest All authors ensure that they have no affiliations or involvement in institutions with any financial or non-financial interest in the matters discussed in this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Many neurons in the central nucleus of the inferior colliculus (IC) show sensitivity to interaural time differences (ITDs), which is thought to be relayed from the brainstem. However, studies with interaural phase modulation of pure tones showed that IC neurons have a sensitivity to changes in ITD that is not present at the level of the brainstem. This sensitivity has been interpreted as a form of sensitivity to motion. A new type of stimulus is used here to study the sensitivity of IC neurons to dynamic changes in ITD, in which broad- or narrowband stimuli are swept through a range of ITDs with arbitrary start-ITD, end-ITD, speed, and direction. Extracellular recordings were obtained under barbiturate anesthesia in the cat. We applied the same analyses as previously introduced for the study of responses to tones. We find effects of motion which are similar to those described in response to interaural phase modulation of tones. The size of the effects strongly depended on the motion parameters but was overall smaller than reported for tones. We found that the effects of motion could largely be explained by the temporal response pattern of the neuron such as adaptation and build-up. Our data add to previous evidence questioning true coding of motion at the level of the IC., (Copyright © 2024. Published by Elsevier B.V.)

Since the presence of tinnitus is not always associated with audiometric hearing loss, it has been hypothesized that hidden hearing loss may act as a potential trigger for increased central gain along the neural pathway leading to tinnitus perception. In recent years, the study of hidden hearing loss has improved with the discovery of cochlear synaptopathy and several objective diagnostic markers. This study investigated three potential markers of peripheral hidden hearing loss in subjects with tinnitus: extended high-frequency audiometric thresholds, the auditory brainstem response, and the envelope following response. In addition, speech intelligibility was measured as a functional outcome measurement of hidden hearing loss. To account for age-related hidden hearing loss, participants were grouped according to age, presence of tinnitus, and audiometric thresholds. Group comparisons were conducted to differentiate between age- and tinnitus-related effects of hidden hearing loss. All three markers revealed age-related differences, whereas no differences were observed between the tinnitus and non-tinnitus groups. However, the older tinnitus group showed improved performance on low-pass filtered speech in noise tests compared to the older non-tinnitus group. These low-pass speech in noise scores were significantly correlated with tinnitus distress, as indicated using questionnaires, and could be related to the presence of hyperacusis. Based on our observations, cochlear synaptopathy does not appear to be the underlying cause of tinnitus. The improvement in low-pass speech-in-noise could be explained by enhanced temporal fine structure encoding or hyperacusis. Therefore, we recommend that future tinnitus research takes into account age-related factors, explores low-frequency encoding, and thoroughly assesses hyperacusis., Competing Interests: Declaration of competing interest none, (Copyright © 2024. Published by Elsevier B.V.)

The round window (RW) membrane plays an important role in normal inner ear mechanics. Occlusion or reinforcement of the RW has been described in the context of congenital anomalies or after cochlear implantation and is applied as a surgical treatment for hyperacusis. Multiple lumped and finite element models predict a low-frequency hearing loss with air conduction of up to 20 dB after RW reinforcement and limited to no effect on hearing with bone conduction stimulation. Experimental verification of these results, however, remains limited. Here, we present an experimental study measuring the impact of RW reinforcement on the middle and inner ear mechanics with air and bone conduction stimulation. In a within-specimen repeated measures design with human cadaveric specimens (n = 6), we compared the intracochlear pressures in scala vestibuli (P SV ) and scala tympani (P ST ) before and after RW reinforcement with soft tissue, cartilage, and bone cement. The differential pressure (P DIFF ) across the basilar membrane - known to be closely related to the hearing sensation - was calculated as the complex difference between P SV and P ST . With air conduction stimulation, both P SV and P ST increased on average up to 22 dB at frequencies below 1500 Hz with larger effect sizes for P ST compared to P SV . The P DIFF , in contrast, decreased up to 11 dB at frequencies between 700 and 800 Hz after reinforcement with bone cement. With bone conduction, the average within-specimen effects were less than 5 dB for either P SV , P ST, or P DIFF . The inter-specimen variability with bone conduction, however, was considerably larger than with air conduction. This experimental study shows that RW reinforcement impacts air conduction stimulation at low frequencies. Bone conduction stimulation seems to be largely unaffected. From a clinical point of view, these results support the hypothesis that delayed loss of air conduction hearing after cochlear implantation could be partially explained by the impact of RW reinforcement., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Although rats and mice are among the preferred animal models for investigating many characteristics of auditory function, they are rarely used to study an essential aspect of binaural hearing: the ability of animals to localize the sources of low-frequency sounds by detecting the interaural time difference (ITD), that is the difference in the time at which the sound arrives at each ear. In mammals, ITDs are mostly encoded in the medial superior olive (MSO), one of the main nuclei of the superior olivary complex (SOC). Because of their small heads and high frequency hearing range, rats and mice are often considered unable to use ITDs for sound localization. Moreover, their MSO is frequently viewed as too small or insignificant compared to that of mammals that use ITDs to localize sounds, including cats and gerbils. However, recent research has demonstrated remarkable similarities between most morphological and physiological features of mouse MSO neurons and those of MSO neurons of mammals that use ITDs. In this context, we have analyzed the structure and neural afferent and efferent connections of the rat MSO, which had never been studied by injecting neuroanatomical tracers into the nucleus. The rat MSO spans the SOC longitudinally. It is relatively small caudally, but grows rostrally into a well-developed column of stacked bipolar neurons. By placing small, precise injections of the bidirectional tracer biotinylated dextran amine (BDA) into the MSO, we show that this nucleus is innervated mainly by the most ventral and rostral spherical bushy cells of the anteroventral cochlear nucleus of both sides, and by the most ventrolateral principal neurons of the ipsilateral medial nucleus of the trapezoid body. The same experiments reveal that the MSO densely innervates the most dorsolateral region of the central nucleus of the inferior colliculus, the central region of the dorsal nucleus of the lateral lemniscus, and the most lateral region of the intermediate nucleus of the lateral lemniscus of its own side. Therefore, the MSO is selectively innervated by, and sends projections to, neurons that process low-frequency sounds. The structural and hodological features of the rat MSO are notably similar to those of the MSO of cats and gerbils. While these similarities raise the question of what functions other than ITD coding the MSO performs, they also suggest that the rat MSO is an appropriate model for future MSO-centered research., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Tinnitus, the perception of sound with no external auditory stimulus, is a complex, multifaceted, and potentially devastating disorder. Despite recent advances in our understanding of tinnitus, there are limited options for effective treatment. Tinnitus treatments are made more complicated by the lack of a test for tinnitus based on objectively measured physiological characteristics. Such an objective test would enable a greater understanding of tinnitus mechanisms and may lead to faster treatment development in both animal and human research. This review makes the argument that an objective tinnitus test, such as a non-invasive electrophysiological measure, is desperately needed. We review the current tinnitus assessment methods, the underlying neural correlates of tinnitus, the multiple tinnitus generation theories, and the previously investigated electrophysiological measurements of tinnitus. Finally, we propose an alternate objective test for tinnitus that may be valid in both animal and human subjects., Competing Interests: Declaration of competing interest The authors have a patent pending for the development of a ‘long-duration sound test’ that could be used as a tool to test for tinnitus., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of perceptual objects from sensory features. Oscillatory activity can be differentiated into stimulus-phase-locked (evoked) and non-phase-locked (induced). The former is mainly determined by sensory input, the latter by higher-level (cortical) processing. Effects of auditory deprivation on cortical oscillations have been studied in congenitally deaf cats (CDCs) using cochlear implant (CI) stimulation. CI-induced alpha, beta, and gamma activity were compromised in the auditory cortex of CDCs. Furthermore, top-down information flow between secondary and primary auditory areas in hearing cats, conveyed by induced alpha oscillations, was lost in CDCs. Here we used the matching pursuit algorithm to assess components of such oscillatory activity in local field potentials recorded in primary field A1. Additionally to the loss of induced alpha oscillations, we also found a loss of evoked theta activity in CDCs. The loss of theta and alpha activity in CDCs can be directly related to reduced high-frequency (gamma-band) activity due to cross-frequency coupling. Here we quantified such cross-frequency coupling in adult 1) hearing-experienced, acoustically stimulated cats (aHCs), 2) hearing-experienced cats following acute pharmacological deafening and subsequent CIs, thus in electrically stimulated cats (eHCs), and 3) electrically stimulated CDCs. We found significant cross-frequency coupling in all animal groups in > 70% of auditory-responsive sites. The predominant coupling in aHCs and eHCs was between theta/alpha phase and gamma power. In CDCs such coupling was lost and replaced by alpha oscillations coupling to delta/theta phase. Thus, alpha/theta oscillations synchronize high-frequency gamma activity only in hearing-experienced cats. The absence of induced alpha and theta oscillations contributes to the loss of induced gamma power in CDCs, thereby signifying impaired local network activity., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hearing loss is well known to cause plastic changes in the central auditory system and pathological changes such as tinnitus and hyperacusis. Impairment of inner ear functions is the main cause of hearing loss. In aged individuals, not only inner ear dysfunction but also senescence of the central nervous system is the cause of malfunction of the auditory system. In most cases of hearing loss, the activity of the auditory nerve is reduced, but that of the successive auditory centers is increased in a compensatory way. It has been reported that activity changes occur in the inferior colliculus (IC), a critical nexus of the auditory pathway. The IC integrates the inputs from the brainstem and drives the higher auditory centers. Since abnormal activity in the IC is likely to affect auditory perception, it is crucial to elucidate the neuronal mechanism to induce the activity changes of IC neurons with hearing loss. This review outlines recent findings on hearing-loss-induced plastic changes in the IC and brainstem auditory neuronal circuits and discusses what neuronal mechanisms underlie hearing-loss-induced changes in the activity of IC neurons. Considering the different causes of hearing loss, we discuss age-related hearing loss separately from other forms of hearing loss (non-age-related hearing loss). In general, the main plastic change of IC neurons caused by both age-related and non-age-related hearing loss is increased central gain. However, plastic changes in the IC caused by age-related hearing loss seem to be more complex than those caused by non-age-related hearing loss., (Copyright © 2024 Elsevier B.V. All rights reserved.)

• There was a statistically significant relationship between IPD-mediated ACC amplitude and behavioral ITD sensitivity for 250 Hz. • ACC N1-P2 responses were significantly higher for 250 Hz versus 1000 Hz. • ACC N1-P2 responses grow with IPD. • The IPD-mediated ACC response may be useful as a biomarker for ITD sensitivity in clinical populations. Combining cochlear implants with binaural acoustic hearing via preserved hearing in the implanted ear(s) is commonly referred to as combined electric and acoustic stimulation (EAS). EAS fittings can provide patients with significant benefit for speech recognition in complex noise, perceived listening difficulty, and horizontal-plane localization as compared to traditional bimodal hearing conditions with contralateral and monaural acoustic hearing. However, EAS benefit varies across patients and the degree of benefit is not reliably related to the underlying audiogram. Previous research has indicated that EAS benefit for speech recognition in complex listening scenarios and localization is significantly correlated with the patients' binaural cue sensitivity, namely interaural time differences (ITD). In the context of pure tones, interaural phase differences (IPD) and ITD can be understood as two perspectives on the same phenomenon. Through simple mathematical conversion, one can be transformed into the other, illustrating their inherent interrelation for spatial hearing abilities. However, assessing binaural cue sensitivity is not part of a clinical assessment battery as psychophysical tasks are time consuming, require training to achieve performance asymptote, and specialized programming and software all of which render this clinically unfeasible. In this study, we investigated the possibility of using an objective measure of binaural cue sensitivity by the acoustic change complex (ACC) via imposition of an IPD of varying degrees at stimulus midpoint. Ten adult listeners with normal hearing were assessed on tasks of behavioral and objective binaural cue sensitivity for carrier frequencies of 250 and 1000 Hz. Results suggest that 1) ACC amplitude increases with IPD; 2) ACC-based IPD sensitivity for 250 Hz is significantly correlated with behavioral ITD sensitivity; 3) Participants were more sensitive to IPDs at 250 Hz as compared to 1000 Hz. Thus, this objective measure of IPD sensitivity may hold clinical application for pre- and post-operative assessment for individuals meeting candidacy indications for cochlear implantation with low-frequency acoustic hearing preservation as this relatively quick and objective measure may provide clinicians with information identifying patients most likely to derive benefit from EAS technology. [ABSTRACT FROM AUTHOR]

• Cholinergic medial olivocochlear neurons are better preserved after long-term cortical electrical stimulation during aging, supporting a role of the efferent system in safeguarding aging progression in the cochlea. • Long-term cortical electrical stimulation during aging results in reduced age-related dystrophic degeneration of the stria vascularis and in inflammation markers, predicting functional recovery. • Long-term cortical electrical stimulation also results in increased calretinin immunolabeling in spiral ganglion neurons, suggesting primed upregulation for excitability modulation, potentially related with hearing loss compensation. • The observed changes induced by long-term cortical electrical simulation in the aging cochlea and brainstem, mirror reported auditory threshold recovery. The auditory cortex is the source of descending connections providing contextual feedback for auditory signal processing at almost all levels of the lemniscal auditory pathway. Such feedback is essential for cognitive processing. It is likely that corticofugal pathways are degraded with aging, becoming important players in age-related hearing loss and, by extension, in cognitive decline. We are testing the hypothesis that surface, epidural stimulation of the auditory cortex during aging may regulate the activity of corticofugal pathways, resulting in modulation of central and peripheral traits of auditory aging. Increased auditory thresholds during ongoing age-related hearing loss in the rat are attenuated after two weeks of epidural stimulation with direct current applied to the surface of the auditory cortex for two weeks in alternate days (Fernández del Campo et al., 2024). Here we report that the same cortical electrical stimulation protocol induces structural and cytochemical changes in the aging cochlea and auditory brainstem, which may underlie recovery of age-degraded auditory sensitivity. Specifically, we found that in 18 month-old rats after two weeks of cortical electrical stimulation there is, relative to age-matched non-stimulated rats: a) a larger number of choline acetyltransferase immunoreactive neuronal cell body profiles in the ventral nucleus of the trapezoid body, originating the medial olivocochlear system.; b) a reduction of age-related dystrophic changes in the stria vascularis; c) diminished immunoreactivity for the pro-inflammatory cytokine TNFα in the stria vascularis and spiral ligament. d) diminished immunoreactivity for Iba1 and changes in the morphology of Iba1 immunoreactive cells in the lateral wall, suggesting reduced activation of macrophage/microglia; d) Increased immunoreactivity levels for calretinin in spiral ganglion neurons, suggesting excitability modulation by corticofugal stimulation. Altogether, these findings support that non-invasive neuromodulation of the auditory cortex during aging preserves the cochlear efferent system and ameliorates cochlear aging traits, including stria vascularis dystrophy, dysregulated inflammation and altered excitability in primary auditory neurons. [Display omitted] [ABSTRACT FROM AUTHOR]

Mutations in the OTOF gene encoding otoferlin result in a disrupted function of the ribbon synapses with impairment of the multivesicular glutamate release. Most affected subjects present with congenital hearing loss and abnormal auditory brainstem potentials associated with preserved cochlear hair cell activities (otoacoustic emissions, cochlear microphonics [CMs]). Transtympanic electrocochleography (ECochG) has recently been proposed for defining the details of potentials arising in both the cochlea and auditory nerve in this disorder, and with a view to shedding light on the pathophysiological mechanisms underlying auditory dysfunction. We review the audiological and electrophysiological findings in children with congenital profound deafness carrying two mutant alleles of the OTOF gene. We show that cochlear microphonic (CM) amplitude and summating potential (SP) amplitude and latency are normal, consistently with a preserved outer and inner hair cell function. In the majority of OTOF children, the SP component is followed by a markedly prolonged low-amplitude negative potential replacing the compound action potential (CAP) recorded in normally-hearing children. This potential is identified at intensities as low as 90 dB below the behavioral threshold. In some ears, a synchronized CAP is superimposed on the prolonged responses at high intensity. Stimulation at high rates reduces the amplitude and duration of the prolonged potentials, consistently with their neural generation. In some children, however, the ECochG response only consists of the SP, with no prolonged potential. Cochlear implants restore hearing sensitivity, speech perception and neural CAP by electrically stimulating the auditory nerve fibers. These findings indicate that an impaired multivesicular glutamate release in OTOF-related disorders leads to abnormal auditory nerve fiber activation and a consequent impairment of spike generation. The magnitude of these effects seems to vary, ranging from no auditory nerve fiber activation to an abnormal generation of EPSPs that occasionally trigger a synchronized electrical activity, resulting in high-threshold CAPs.

Cochlear implants are medical devices that have restored hearing to approximately one million people around the world. Outcomes are impressive and most recipients attain excellent speech comprehension in quiet without relying on lip-reading cues, but pitch resolution is poor compared to normal hearing. Amplitude modulation of electrical stimulation is a primary cue for pitch perception in cochlear implant users. The experiments described in this article focus on the relationship between sensitivity to amplitude modulations and pitch resolution based on changes in the frequency of amplitude modulations. In the first experiment, modulation sensitivity and pitch resolution were measured in adults with no known hearing loss and in cochlear implant users with sounds presented to and processed by their clinical devices. Stimuli were amplitude-modulated sinusoids and amplitude-modulated narrow-band noises. Modulation detection and modulation frequency discrimination were measured for modulation frequencies centered on 110, 220, and 440 Hz. Pitch resolution based on changes in modulation frequency was measured for modulation depths of 25 %, 50 %, 100 %, and for a half-waved rectified modulator. Results revealed a strong linear relationship between modulation sensitivity and pitch resolution for cochlear implant users and peers with no known hearing loss. In the second experiment, cochlear implant users took part in analogous procedures of modulation sensitivity and pitch resolution but bypassing clinical sound processing using single-electrode stimulation. Results indicated that modulation sensitivity and pitch resolution was better conveyed by single-electrode stimulation than by clinical processors. Results at 440 Hz were worse, but also not well conveyed by clinical sound processing, so it remains unclear whether the 300 Hz perceptual limit described in the literature is a technological or biological limitation. These results highlight modulation depth and sensitivity as critical factors for pitch resolution in cochlear implant users and characterize the relationship that should inform the design of modulation enhancement algorithms for cochlear implants., (Copyright © 2024. Published by Elsevier B.V.)

In recent studies, psychophysiological measures have been used as markers of listening effort, but there is limited research on the effect of hearing loss on such measures. The aim of the current study was to investigate the effect of hearing acuity on physiological responses and subjective measures acquired during different levels of listening demand, and to investigate the relationship between these measures. A total of 125 participants (37 males and 88 females, age range 37-72 years, pure-tone average hearing thresholds at the best ear between -5.0 to 68.8 dB HL and asymmetry between ears between 0.0 and 87.5 dB) completed a listening task. A speech reception threshold (SRT) test was used with target sentences spoken by a female voice masked by male speech. Listening demand was manipulated using three levels of intelligibility: 20 % correct speech recognition, 50 %, and 80 % (IL20 %/IL50 %/IL80 %, respectively). During the task, peak pupil dilation (PPD), heart rate (HR), pre-ejection period (PEP), respiratory sinus arrhythmia (RSA), and skin conductance level (SCL) were measured. For each condition, subjective ratings of effort, performance, difficulty, and tendency to give up were also collected. Linear mixed effects models tested the effect of intelligibility level, hearing acuity, hearing asymmetry, and tinnitus complaints on the physiological reactivity (compared to baseline) and subjective measures. PPD and PEP reactivity showed a non-monotonic relationship with intelligibility level, but no such effects were found for HR, RSA, or SCL reactivity. Participants with worse hearing acuity had lower PPD at all intelligibility levels and showed lower PEP baseline levels. Additionally, PPD and SCL reactivity were lower for participants who reported suffering from tinnitus complaints. For IL80 %, but not IL50 % or IL20 %, participants with worse hearing acuity rated their listening effort to be relatively high compared to participants with better hearing. The reactivity of the different physiological measures were not or only weakly correlated with each other. Together, the results suggest that hearing acuity may be associated with altered sympathetic nervous system (re)activity. Research using psychophysiological measures as markers of listening effort to study the effect of hearing acuity on such measures are best served by the use of the PPD and PEP., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Older listeners have difficulty processing temporal cues that are important for word discrimination, and deficient processing may limit their ability to benefit from these cues. Here, we investigated aging effects on perception and neural representation of the consonant transition and the factors that contribute to successful perception. To further understand the neural mechanisms underlying the changes in processing from brainstem to cortex, we also examined the factors that contribute to exaggerated amplitudes in cortex. We enrolled 30 younger normal-hearing and 30 older normal-hearing participants who met the criteria of clinically normal hearing. Perceptual identification functions were obtained for the words BEAT and WHEAT on a 7-step continuum of consonant-transition duration. Auditory brainstem responses (ABRs) were recorded to click stimuli and frequency-following responses (FFRs) and cortical auditory-evoked potentials were recorded to the endpoints of the BEAT-WHEAT continuum. Perceptual performance for identification of BEAT vs. WHEAT did not differ between younger and older listeners. However, both subcortical and cortical measures of neural representation showed age group differences, such that FFR phase locking was lower but cortical amplitudes (P1 and N1) were higher in older compared to younger listeners. ABR Wave I amplitude and FFR phase locking, but not audiometric thresholds, predicted early cortical amplitudes. Phase locking to the transition region and early cortical peak amplitudes (P1) predicted performance on the perceptual identification function. Overall, results suggest that the neural representation of transition durations and cortical overcompensation may contribute to the ability to perceive transition duration contrasts. Cortical overcompensation appears to be a maladaptive response to decreased neural firing/synchrony., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite that fact that the cochlear implant (CI) is one of the most successful neuro-prosthetic devices which allows hearing restoration, several aspects still need to be improved. Interactions between stimulating electrodes through current spread occurring within the cochlea drastically limit the number of discriminable frequency channels and thus can ultimately result in poor speech perception. One potential solution relies on the use of new pulse shapes, such as asymmetric pulses, which can potentially reduce the current spread within the cochlea. The present study characterized the impact of changing electrical pulse shapes from the standard biphasic symmetric to the asymmetrical shape by quantifying the evoked firing rate and the spatial activation in the guinea pig primary auditory cortex (A1). At a fixed charge, the firing rate and the spatial activation in A1 decreased by 15 to 25 % when asymmetric pulses were used to activate the auditory nerve fibers, suggesting a potential reduction of the spread of excitation inside the cochlea. A strong "polarity-order" effect was found as the reduction was more pronounced when the first phase of the pulse was cathodic with high amplitude. These results suggest that the use of asymmetrical pulse shapes in clinical settings can potentially reduce the channel interactions in CI users., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Understanding the complex pathologies associated with hearing loss is a significant motivation for conducting inner ear research. Lifelong exposure to loud noise, ototoxic drugs, genetic diversity, sex, and aging collectively contribute to human hearing loss. Replicating this pathology in research animals is challenging because hearing impairment has varied causes and different manifestations. A central aspect, however, is the loss of sensory hair cells and the inability of the mammalian cochlea to replace them. Researching therapeutic strategies to rekindle regenerative cochlear capacity, therefore, requires the generation of animal models in which cochlear hair cells are eliminated. This review discusses different approaches to ablate cochlear hair cells in adult mice. We inventoried the cochlear cyto- and histo-pathology caused by acoustic overstimulation, systemic and locally applied drugs, and various genetic tools. The focus is not to prescribe a perfect damage model but to highlight the limitations and advantages of existing approaches and identify areas for further refinement of damage models for use in regenerative studies., (Copyright © 2024. Published by Elsevier B.V.)

This study introduces and evaluates the PHAST+ model, part of a computational framework designed to simulate the behavior of auditory nerve fibers in response to the electrical stimulation from a cochlear implant. PHAST+ incorporates a highly efficient method for calculating accommodation and adaptation, making it particularly suited for simulations over extended stimulus durations. The proposed method uses a leaky integrator inspired by classic biophysical nerve models. Through evaluation against single-fiber animal data, our findings demonstrate the model's effectiveness across various stimuli, including short pulse trains with variable amplitudes and rates. Notably, the PHAST+ model performs better than its predecessor, PHAST (a phenomenological model by van Gendt et al.), particularly in simulations of prolonged neural responses. While PHAST+ is optimized primarily on spike rate decay, it shows good behavior on several other neural measures, such as vector strength and degree of adaptation. The future implications of this research are promising. PHAST+ drastically reduces the computational burden to allow the real-time simulation of neural behavior over extended periods, opening the door to future simulations of psychophysical experiments and multi-electrode stimuli for evaluating novel speech-coding strategies for cochlear implants., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cortical acetylcholine (ACh) release has been linked to various cognitive functions, including perceptual learning. We have previously shown that cortical cholinergic innervation is necessary for accurate sound localization in ferrets, as well as for their ability to adapt with training to altered spatial cues. To explore whether these behavioral deficits are associated with changes in the response properties of cortical neurons, we recorded neural activity in the primary auditory cortex (A1) of anesthetized ferrets in which cholinergic inputs had been reduced by making bilateral injections of the immunotoxin ME20.4-SAP in the nucleus basalis (NB) prior to training the animals. The pattern of spontaneous activity of A1 units recorded in the ferrets with cholinergic lesions (NB ACh - ) was similar to that in controls, although the proportion of burst-type units was significantly lower. Depletion of ACh also resulted in more synchronous activity in A1. No changes in thresholds, frequency tuning or in the distribution of characteristic frequencies were found in these animals. When tested with normal acoustic inputs, the spatial sensitivity of A1 neurons in the NB ACh - ferrets and the distribution of their preferred interaural level differences also closely resembled those found in control animals, indicating that these properties had not been altered by sound localization training with one ear occluded. Simulating the animals' previous experience with a virtual earplug in one ear reduced the contralateral preference of A1 units in both groups, but caused azimuth sensitivity to change in slightly different ways, which may reflect the modest adaptation observed in the NB ACh - group. These results show that while ACh is required for behavioral adaptation to altered spatial cues, it is not required for maintenance of the spectral and spatial response properties of A1 neurons., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew J King reports financial support was provided by Wellcome Trust. Victoria M Bajo reports financial support was provided by Royal National Institute for Deaf People. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r = -0.407), but noise exposure effects are weak (r = -0.152). We conclude that noise exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Limited auditory input, whether caused by hearing loss or by electrical stimulation through a cochlear implant (CI), can be compensated by the remaining senses. Specifically for CI users, previous studies reported not only improved visual skills, but also altered cortical processing of unisensory visual and auditory stimuli. However, in multisensory scenarios, it is still unclear how auditory deprivation (before implantation) and electrical hearing experience (after implantation) affect cortical audiovisual speech processing. Here, we present a prospective longitudinal electroencephalography (EEG) study which systematically examined the deprivation- and CI-induced alterations of cortical processing of audiovisual words by comparing event-related potentials (ERPs) in postlingually deafened CI users before and after implantation (five weeks and six months of CI use). A group of matched normal-hearing (NH) listeners served as controls. The participants performed a word-identification task with congruent and incongruent audiovisual words, focusing their attention on either the visual (lip movement) or the auditory speech signal. This allowed us to study the (top-down) attention effect on the (bottom-up) sensory cortical processing of audiovisual speech. When compared to the NH listeners, the CI candidates (before implantation) and the CI users (after implantation) exhibited enhanced lipreading abilities and an altered cortical response at the N1 latency range (90-150 ms) that was characterized by a decreased theta oscillation power (4-8 Hz) and a smaller amplitude in the auditory cortex. After implantation, however, the auditory-cortex response gradually increased and developed a stronger intra-modal connectivity. Nevertheless, task efficiency and activation in the visual cortex was significantly modulated in both groups by focusing attention on the visual as compared to the auditory speech signal, with the NH listeners additionally showing an attention-dependent decrease in beta oscillation power (13-30 Hz). In sum, these results suggest remarkable deprivation effects on audiovisual speech processing in the auditory cortex, which partially reverse after implantation. Although even experienced CI users still show distinct audiovisual speech processing compared to NH listeners, pronounced effects of (top-down) direction of attention on (bottom-up) audiovisual processing can be observed in both groups. However, NH listeners but not CI users appear to show enhanced allocation of cognitive resources in visually as compared to auditory attended audiovisual speech conditions, which supports our behavioural observations of poorer lipreading abilities and reduced visual influence on audition in NH listeners as compared to CI users., (Copyright © 2024. Published by Elsevier B.V.)

Auditory nerve (AN) fibers that innervate inner hair cells in the cochlea degenerate with advancing age. It has been proposed that age-related reductions in brainstem frequency-following responses (FFR) to the carrier of low-frequency, high-intensity pure tones may partially reflect this neural loss in the cochlea (Märcher-Rørsted et al., 2022). If the loss of AN fibers is the primary factor contributing to age-related changes in the brainstem FFR, then the FFR could serve as an indicator of cochlear neural degeneration. In this study, we employed electrocochleography (ECochG) to investigate the effects of age on frequency-following neurophonic potentials, i.e., neural responses phase-locked to the carrier frequency of the tone stimulus. We compared these findings to the brainstem-generated FFRs obtained simultaneously using the same stimulation. We conducted recordings in young and older individuals with normal hearing. Responses to pure tones (250 ms, 516 and 1086 Hz, 85 dB SPL) and clicks were recorded using both ECochG at the tympanic membrane and traditional scalp electroencephalographic (EEG) recordings of the FFR. Distortion product otoacoustic emissions (DPOAE) were also collected. In the ECochG recordings, sustained AN neurophonic (ANN) responses to tonal stimulation, as well as the click-evoked compound action potential (CAP) of the AN, were significantly reduced in the older listeners compared to young controls, despite normal audiometric thresholds. In the EEG recordings, brainstem FFRs to the same tone stimulation were also diminished in the older participants. Unlike the reduced AN CAP response, the transient-evoked wave-V remained unaffected. These findings could indicate that a decreased number of AN fibers contributes to the response in the older participants. The results suggest that the scalp-recorded FFR, as opposed to the clinical standard wave-V of the auditory brainstem response, may serve as a more reliable indicator of age-related cochlear neural degeneration., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The use of cochlear implants (CIs) is on the rise for patients with vestibular schwannoma (VS). Besides CI following tumor resection, new scenarios such as implantation in observed and/or irradiated tumors are becoming increasingly common. A significant emerging trend is the need of intraoperative evaluation of the functionality of the cochlear nerve in order to decide if a CI would be placed. The purpose of this paper is to explore the experience of a tertiary center with the application of the Auditory Nerve Test System (ANTS) in various scenarios regarding VS patients. The results are compared to that of the studies that have previously used the ANTS in this condition. Patients with unilateral or bilateral VS (NF2) who were evaluated with the ANTS prior to considering CI in a tertiary center between 2021 and 2023 were analyzed. The presence of a robust wave V was chosen to define a positive electrical auditory brainstem response (EABR). Two patients underwent promontory stimulation (PromStim) EABR previous to ANTS evaluation. Seven patients, 2 NF-2 and 5 with sporadic VS were included. The initial scenario was simultaneous translabyrinthine (TL) tumor resection and CI in 3 cases while a CI placement without tumor resection was planned in 4 cases. The ANTS was positive in 4 cases, negative in 2 cases, and uncertain in one case. Two patients underwent simultaneous TL and CI, 1 patient simultaneous TL and auditory brainstem implant, 3 patients posterior tympanotomy with CI, and 1 patient had no implant placement. In the 5 patients undergoing CI, sound detection was present. There was a good correlation between the PromStim and ANTS EABR. The literature research yielded 35 patients with complete information about EABR response. There was one false negative and one false positive case; that is, the 28 implanted cases with a present wave V following tumor resection had some degree of auditory perception in all but one case. The ANTS is a useful intraoperative tool to asses CI candidacy in VS patients undergoing observation, irradiation or surgery. A positive strongly predicts at least sound detection with the CI., Competing Interests: Declaration of competing interest Miguel Díaz is employed at MED-EL as a clinical engineer; this function entails support during surgery. MED-EL was not involved in the study design, collection and analysis of data or the decision to submit it for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite the proven effectiveness of cochlear implant (CI) in the hearing restoration of deaf or hard-of-hearing (DHH) children, to date, extreme variability in verbal working memory (VWM) abilities is observed in both unilateral and bilateral CI user children (CIs). Although clinical experience has long observed deficits in this fundamental executive function in CIs, the cause to date is still unknown. Here, we have set out to investigate differences in brain functioning regarding the impact of monaural and binaural listening in CIs compared with normal hearing (NH) peers during a three-level difficulty n-back task undertaken in two sensory modalities (auditory and visual). The objective of this pioneering study was to identify electroencephalographic (EEG) marker pattern differences in visual and auditory VWM performances in CIs compared to NH peers and possible differences between unilateral cochlear implant (UCI) and bilateral cochlear implant (BCI) users. The main results revealed differences in theta and gamma EEG bands. Compared with hearing controls and BCIs, UCIs showed hypoactivation of theta in the frontal area during the most complex condition of the auditory task and a correlation of the same activation with VWM performance. Hypoactivation in theta was also observed, again for UCIs, in the left hemisphere when compared to BCIs and in the gamma band in UCIs compared to both BCIs and NHs. For the latter two, a correlation was found between left hemispheric gamma oscillation and performance in the audio task. These findings, discussed in the light of recent research, suggest that unilateral CI is deficient in supporting auditory VWM in DHH. At the same time, bilateral CI would allow the DHH child to approach the VWM benchmark for NH children. The present study suggests the possible effectiveness of EEG in supporting, through a targeted approach, the diagnosis and rehabilitation of VWM in DHH children., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Although the cochlear implant has been widely acknowledged as the most successful neural prosthesis, only a fraction of hearing-impaired people who can potentially benefit from a cochlear implant have actually received one due to its limited awareness, accessibility, and affordability. To help overcome these limitations, a 26-electrode cochlear implant has been developed to receive China's Food and Drug Administration (CFDA) approval in 2011 and Conformité Européenne (CE) Marking in 2012. The present article describes design philosophy, system specification, and technical verification of the Nurotron device, which includes advanced digital signal processing and 4 current sources with multiple amplitude resolutions that not only are compatible with perceptual capability but also allow interleaved or simultaneous stimulation. The article also presents 3-year longitudinal evaluation data from 60 human subjects who have received the Nurotron device. The objective measures show that electrode impedance decreased within the first month of device use, but was stable until a slight increase at the end of two years. The subjective loudness measures show that electric stimulation threshold was stable while the maximal comfort level increased over the 3 years. Mandarin sentence recognition increased from the pre-surgical 0%-correct score to a plateau of about 80% correct with 6-month use of the device. Both indirect and direct comparisons indicate indistinguishable performance differences between the Nurotron system and other commercially available devices. The present 26-electrode cochlear implant has already helped to lower the price of cochlear implantation in China and will likely contribute to increased cochlear implant access and success in the rest of the world. This article is part of a Special Issue entitled .

• Significant ABRs threshold shifts in an albino Wistar rat spontaneous aging model are first detected at 16 months of age. • In our model of spontaneous aging, medium frequencies are less affected in the inner ear. • Long-term, multi-session, epidural DC stimulation applied in AC at the onset of presbycusis delays the progression of ARHL. • After AC electric stimulation, pure tone ABR recordings suggest stability in cochlear tonotopic analysis in our model of spontaneous age-related hearing loss (ARHL). Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis. [ABSTRACT FROM AUTHOR]

• A comprehensive analysis of different cochlear implant stimulation parameters was conducted using direct comparisons. • Spread of Excitation is decreased using current focusing, but not common ground configuration, while thresholds increase with both. • Compared to conventional stimulation, channel interactions are reduced using current focusing, duration coding, or pseudomonophasic stimulation. • A reduction of the second stimulus phase improved virtually all measured parameters. • These results argue that conventional CI stimulation could be improved in multiple ways. The present study investigates effects of current focusing and pulse shape on threshold, dynamic range, spread of excitation and channel interaction in the time domain using cochlear implant stimulation. The study was performed on 20 adult guinea pigs using a 6-channel animal cochlear implant, recording was performed in the auditory midbrain using a multielectrode array. After determining the best frequencies for individual recording contacts with acoustic stimulation, the ear was deafened and a cochlear implant was inserted into the cochlea. The position of the implant was controlled by x-ray. Stimulation with biphasic, pseudomonophasic and monophasic stimuli was performed with monopolar, monopolar with common ground, bipolar and tripolar configuration in two sets of experiments, allowing comparison of the effects of the different stimulation strategies on threshold, dynamic range, spread of excitation and channel interaction. Channel interaction was studied in the temporal domain, where two electrodes were activated with pulse trains and phase locking to these pulse trains in the midbrain was quantified. The results documented multifactorial influences on the response properties, with significant interaction between factors. Thresholds increased with increasing current focusing, but decreased with pseudomonophasic and monophasic pulse shapes. The results documented that current focusing, particularly tripolar configuration, effectively reduces channel interaction, but that also pseudomonophasic and monophasic stimulation and phase duration intensity coding reduce channel interactions. [ABSTRACT FROM AUTHOR]

The perception of the distance to a sound source is relevant in many everyday situations, not only in real spaces, but also in virtual reality (VR) environments. Where real rooms often reach their limits, VR offers far-reaching possibilities to simulate a wide range of acoustic scenarios. However, in virtual room acoustics a plausible reproduction of distance-related cues can be challenging. In the present study, we compared the detection of changes of the distance to a sound source and its neurocognitive correlates in a real and a virtual reverberant environment, using an active auditory oddball paradigm and EEG measures. The main goal was to test whether the experiments in the virtual and real environments produced equivalent behavioral and EEG results. Three loudspeakers were placed at ego-centric distances of 2 m (near), 4 m (center), and 8 m (far) in front of the participants (N = 20), each 66 cm below their ear level. Sequences of 500 ms noise stimuli were presented either from the center position (standards, 80 % of trials) or from the near or far position (targets, 10 % each). The participants had to indicate a target position via a joystick response ("near" or "far"). Sounds were emitted either by real loudspeakers in the real environment or rendered and played back for the corresponding positions via headphones in the virtual environment. In addition, within both environments, loudness of the auditory stimuli was either unaltered (natural loudness) or the loudness cue was manipulated, so that all three loudspeakers were perceived equally loud at the listener's position (matched loudness). The EEG analysis focused on the mismatch negativity (MMN), P3a, and P3b as correlates of deviance detection, attentional orientation, and context-updating/stimulus evaluation, respectively. Overall, behavioral data showed that detection of the target positions was reduced within the virtual environment, and especially when loudness was matched. Except for slight latency shifts in the virtual environment, EEG analysis indicated comparable patterns within both environments and independent of loudness settings. Thus, while the neurocognitive processing of changes in distance appears to be similar in virtual and real spaces, a proper representation of loudness appears to be crucial to achieve a good task performance in virtual acoustic environments., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Auditory semantic novelty - a new meaningful sound in the context of a predictable acoustical environment - can probe neural circuits involved in language processing. Aberrant novelty detection is a feature of many neuropsychiatric disorders. This large-scale human intracranial electrophysiology study examined the spatial distribution of gamma and alpha power and auditory evoked potentials (AEP) associated with responses to unexpected words during performance of semantic categorization tasks. Participants were neurosurgical patients undergoing monitoring for medically intractable epilepsy. Each task included repeatedly presented monosyllabic words from different talkers ("common") and ten words presented only once ("novel"). Targets were words belonging to a specific semantic category. Novelty effects were defined as differences between neural responses to novel and common words. Novelty increased task difficulty and was associated with augmented gamma, suppressed alpha power, and AEP differences broadly distributed across the cortex. Gamma novelty effect had the highest prevalence in planum temporale, posterior superior temporal gyrus (STG) and pars triangularis of the inferior frontal gyrus; alpha in anterolateral Heschl's gyrus (HG), anterior STG and middle anterior cingulate cortex; AEP in posteromedial HG, lower bank of the superior temporal sulcus, and planum polare. Gamma novelty effect had a higher prevalence in dorsal than ventral auditory-related areas. Novelty effects were more pronounced in the left hemisphere. Better novel target detection was associated with reduced gamma novelty effect within auditory cortex and enhanced gamma effect within prefrontal and sensorimotor cortex. Alpha and AEP novelty effects were generally more prevalent in better performing participants. Multiple areas, including auditory cortex on the superior temporal plane, featured AEP novelty effect within the time frame of P3a and N400 scalp-recorded novelty-related potentials. This work provides a detailed account of auditory novelty in a paradigm that directly examined brain regions associated with semantic processing. Future studies may aid in the development of objective measures to assess the integrity of semantic novelty processing in clinical populations., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Age-related auditory dysfunction, presbycusis, is caused in part by functional changes in the auditory cortex (ACtx) such as altered response dynamics and increased population correlations. Given the ability of cortical function to be altered by training, we tested if performing auditory tasks might benefit auditory function in old age. We examined this by training adult mice on a low-effort tone-detection task for at least six months and then investigated functional responses in ACtx at an older age (∼18 months). Task performance remained stable well into old age. Comparing sound-evoked responses of thousands of ACtx neurons using in vivo 2-photon Ca 2+ imaging, we found that many aspects of youthful neuronal activity, including low activity correlations, lower neural excitability, and a greater proportion of suppressed responses, were preserved in trained old animals as compared to passively-exposed old animals. Thus, consistent training on a low-effort task can benefit age-related functional changes in ACtx and may preserve many aspects of auditory function., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Data from non-human primates can help extend observations from non-primate species to humans. Here we report measurements on the auditory nerve of macaque monkeys in the context of a controversial topic important to human hearing. A range of techniques have been used to examine the claim, which is not generally accepted, that human frequency tuning is sharper than traditionally thought, and sharper than in commonly used animal models. Data from single auditory-nerve fibers occupy a pivotal position to examine this claim, but are not available for humans. A previous study reported sharper tuning in auditory-nerve fibers of macaque relative to the cat. A limitation of these and other single-fiber data is that frequency selectivity was measured with tonal threshold-tuning curves, which do not directly assess spectral filtering and whose shape is sharpened by cochlear nonlinearity. Our aim was to measure spectral filtering with wideband suprathreshold stimuli in the macaque auditory nerve. We obtained responses of single nerve fibers of anesthetized macaque monkeys and cats to a suprathreshold, wideband, multicomponent stimulus designed to allow characterization of spectral filtering at any cochlear locus. Quantitatively the differences between the two species are smaller than in previous studies, but consistent with these studies the filters obtained show a trend of sharper tuning in macaque, relative to the cat, for fibers in the basal half of the cochlea. We also examined differences in group delay measured on the phase data near the characteristic frequency versus in the low-frequency tail. The phase data are consistent with the interpretation of sharper frequency tuning in monkey in the basal half of the cochlea. We conclude that use of suprathreshold, wide-band stimuli supports the interpretation of sharper frequency selectivity in macaque nerve fibers relative to the cat, although the difference is less marked than apparent from the assessment with tonal threshold-based data., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)