Hearing Research最新文献

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.

Delayed loss of residual acoustic hearing after cochlear implantation is a common but poorly understood phenomenon due to the scarcity of relevant temporal bone tissues. Prior histopathological analysis of one case of post-implantation hearing loss suggested there were no interaural differences in hair cell or neural degeneration to explain the profound loss of low-frequency hearing on the implanted side (Quesnel et al., 2016) and attributed the threshold elevation to neo-ossification and fibrosis around the implant. Here we re-evaluated the histopathology in this case, applying immunostaining and improved microscopic techniques for differentiating surviving hair cells from supporting cells. The new analysis revealed dramatic interaural differences, with a > 80 % loss of inner hair cells in the cochlear apex on the implanted side, which can account for the post-implantation loss of residual hearing. Apical degeneration of the stria further contributed to threshold elevation on the implanted side. In contrast, spiral ganglion cell survival was reduced in the region of the electrode on the implanted side, but apical counts in the two ears were similar to that seen in age-matched unimplanted control ears. Almost none of the surviving auditory neurons retained peripheral axons throughout the basal half of the cochlea. Relevance to cochlear implant performance is discussed.

Amplitude modulation is an important acoustic cue for sound discrimination, and humans and animals are able to detect small modulation depths behaviorally. In the inferior colliculus (IC), both firing rate and phase-locking may be used to detect amplitude modulation. How neural representations that detect modulation change with age are poorly understood, including the extent to which age-related changes may be attributed to the inherited properties of ascending inputs to IC neurons. Here, simultaneous measures of local field potentials (LFPs) and single-unit responses were made from the inferior colliculus of Young and Aged rats using both noise and tone carriers in response to sinusoidally amplitude-modulated sounds of varying depths. We found that Young units had higher firing rates than Aged for noise carriers, whereas Aged units had higher phase-locking (vector strength), especially for tone carriers. Sustained LFPs were larger in Young animals for modulation frequencies 8–16 Hz and comparable at higher modulation frequencies. Onset LFP amplitudes were much larger in Young animals and were correlated with the evoked firing rates, while LFP onset latencies were shorter in Aged animals. Unit neurometric thresholds by synchrony or firing rate measures did not differ significantly across age and were comparable to behavioral thresholds in previous studies whereas LFP thresholds were lower than behavior.

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.

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.

Cisplatin, a highly effective chemotherapeutic drug for various human cancers, induces irreversible sensorineural hearing loss as a side effect. Currently there are no highly effective clinical strategies for the prevention of cisplatin-induced ototoxicity. Previous studies have indicated that short-term cisplatin ototoxicity primarily affects the outer hair cells of the cochlea. Therefore, preventing the entry of cisplatin into hair cells may be a promising strategy to prevent cisplatin ototoxicity. This study aimed to investigate the entry route of cisplatin into mouse cochlear hair cells. The competitive inhibitor of organic cation transporter 2 (OCT2), cimetidine, and the sensory mechanoelectrical transduction (MET) channel blocker benzamil, demonstrated a protective effect against cisplatin toxicity in hair cells in cochlear explants. Sensory MET-deficient hair cells explanted from Tmc1^Δ;Tmc2^Δ mice were resistant to cisplatin toxicity. Cimetidine showed an additive protective effect against cisplatin toxicity in sensory MET-deficient hair cells. However, in the apical turn, cimetidine, benzamil, or genetic ablation of sensory MET channels showed limited protective effects, implying the presence of other entry routes for cisplatin to enter the hair cells in the apical turn. Systemic administration of cimetidine failed to protect cochlear hair cells from ototoxicity caused by systemically administered cisplatin. Notably, outer hair cells in MET-deficient mice exhibited no apparent deterioration after systemic administration of cisplatin, whereas the outer hair cells in wild-type mice showed remarkable deterioration. The susceptibility of mouse cochlear hair cells to cisplatin ototoxicity largely depends on the sensory MET channel both ex vivo and in vivo. This result justifies the development of new pharmaceuticals, such as a specific antagonists for sensory MET channels or custom-designed cisplatin analogs which are impermeable to sensory MET channels.

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.

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.

The disruption of ribbon synapses in the cochlea impairs the transmission of auditory signals from the cochlear sensory receptor cells to the auditory cortex. Although cisplatin-induced loss of ribbon synapses is well-documented, and studies have reported nitration of cochlear proteins after cisplatin treatment, yet the underlying mechanism of cochlear synaptopathy is not fully understood. This study tests the hypothesis that cisplatin treatment alters the abundance of cochlear synaptosomal proteins, and selective targeting of nitrative stress prevents the associated synaptic dysfunction. Auditory brainstem responses of mice treated with cisplatin showed a reduction in amplitude and an increase in latency of wave I, indicating cisplatin-induced synaptic dysfunction. The mass spectrometry analysis of cochlear synaptosomal proteins identified 102 proteins that decreased in abundance and 249 that increased in abundance after cisplatin treatment. Pathway analysis suggested that the dysregulated proteins were involved in calcium binding, calcium ion regulation, synapses, and endocytosis pathways. Inhibition of nitrative stress by co-treatment with MnTBAP, a peroxynitrite scavenger, attenuated cisplatin-induced changes in the abundance of 27 proteins. Furthermore, MnTBAP co-treatment prevented the cisplatin-induced decrease in the amplitude and increase in the latency of wave I. Together, these findings suggest a potential role of oxidative/nitrative stress in cisplatin-induced cochlear synaptic dysfunction.

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.