Auditory Research publications

A previous investigation demonstrated differences between younger adult normal-hearing listeners and older adult hearing-impaired listeners in the perceived emotion of clear and conversational speech. Specifically, clear speech sounded angry more often than conversational speech for both groups, but the effect was smaller for the older listeners. These listener groups differed by two confounding factors, age (younger vs. older adults) and hearing status (normal vs. impaired). The objective of the present study was to evaluate the contributions of aging and hearing loss to the reduced perception of anger in older adults with hearing loss. We investigated perceived anger in clear and conversational speech in younger adults with and without a simulated age-related hearing loss, and in older adults with normal hearing. Younger adults with simulated hearing loss performed similarly to normal-hearing peers, while normal-hearing older adults performed similarly to hearing-impaired peers, suggesting that aging was the primary contributor to the decreased anger perception seen in previous work. These findings confirm reduced anger perception for older adults compared to younger adults, though the significant speaking style effect—regardless of age and hearing status—highlights the need to identify methods of producing clear speech that is emotionally neutral or positive.

Across-frequency binaural interference occurs when the sensitivity to changes in interaural differences in a target sound is decreased by a spectrally remote diotic interfering sound. For interaural time differences (ITDs), low-frequency (e.g., 0.5 kHz) interferers cause more interference on high-frequency (e.g., 4 kHz) targets than vice versa. For interaural level differences (ILDs), however, it is unclear if a frequency dependence exists. Therefore, ILD discrimination thresholds and across-frequency binaural interference were measured for target and interferer frequencies between 0.5 and 8 kHz (for tones) or 12 kHz (for narrowband noises). For tones, 8-kHz targets experienced the least interference and 8-kHz interferers produced the most interference, suggesting that higher-frequency ILDs are a more heavily weighted localization cue than lower-frequency ILDs. For narrowband noises, the frequency-dependent interference patterns increased in complexity in comparison to tones. Low-frequency ITD dominance (from randomly varying onset ITDs) and grouping cues (e.g., envelope modulations) might explain some of the complexity in the interference patterns for the noises. These data contribute to a better understanding of across-frequency ILD processing, which remains poorly understood.

The primary startle response (SR) is an innate reaction evoked by sudden and intense acoustic, tactile or visual stimuli. In rodents and humans the SR involves reflexive contractions of the face, neck and limb muscles. The acoustic startle response (ASR) pathway consists of auditory nerve fibers (AN), cochlear root neurons (CRNs) and giant neurons of the caudal pontine reticular nucleus (PnC), which synapse on cranial and spinal motor neurons. The tactile startle response (TSR) is transmitted by primary sensory neurons to the principal sensory (Pr5) and spinal (Sp5) trigeminal nuclei. The ventral part of Pr5 projects directly to the PnC neurons. The SR requires rapid transmission of sensory information to initiate a fast motor response. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) are necessary to transmit auditory information to the PnC neurons and elicit the SR. AMPARs containing the glutamate AMPAR subunit 4 (GluA4) have fast kinetics, which makes them ideal candidates to transmit the SR signal. This study examined the role of GluA4 within the primary SR pathway by using GluA4 knockout (GluA4-KO) mice. Deletion of GluA4 considerably decreased the amplitude and probability of successful ASR and TSR, indicating that the presence of this subunit is critical at a common station within the startle pathway. We conclude that deletion of GluA4 affects the transmission of sensory signals from acoustic and tactile pathways to the motor component of the startle reflex. Therefore, GluA4 is required for the full response and for reliable elicitation of the startle response.

Moderate noise exposure may cause acute loss of cochlear synapses without affecting the cochlear hair cells and hearing threshold; thus, it remains "hidden" to standard clinical tests. This cochlear synaptopathy is one of the main pathologies of noise-induced hearing loss (NIHL). There is no effective treatment for NIHL, mainly because of the lack of a proper drug-delivery technique. We hypothesized that local magnetic delivery of gene therapy into the inner ear could be beneficial for NIHL. In this study, we used superparamagnetic iron oxide nanoparticles (SPIONs) and a recombinant adeno-associated virus (AAV) vector (AAV2(quad Y-F)) to deliver brain-derived neurotrophic factor (BDNF) gene therapy into the rat inner ear via minimally invasive magnetic targeting. We found that the magnetic targeting effectively accumulates and distributes the SPION-tagged AAV2(quad Y-F)-BDNF vector into the inner ear. We also found that AAV2(quad Y-F) efficiently transfects cochlear hair cells and enhances BDNF gene expression. Enhanced BDNF gene expression substantially recovers noise-induced BDNF gene downregulation, auditory brainstem response (ABR) wave I amplitude reduction, and synapse loss. These results suggest that magnetic targeting of AAV2(quad Y-F)-mediated BDNF gene therapy could reverse cochlear synaptopathy after NIHL.

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant risk gene thought to play a role in the genetic etiology of language-related disorders, such as autism spectrum disorder and developmental language disorder. Despite its candidacy for influencing language development, few preclinical studies have examined the role of CNTNAP2 in auditory processing. Using in vivo and in vitro electrophysiological recordings in a rat model with translational validity, we report that a loss of the Cntnap2 gene function caused immature-like cortical evoked potentials, delayed multiunit response latencies to acoustic stimuli, impaired temporal processing, and led to a pattern of hyperexcitability in both multiunit and single cell recordings in adulthood. These collective results provide direct evidence that a constitutive loss of Cntnap2 gene function in rats can cause auditory processing impairments similar to those seen in language-related human disorders, indicating that its contribution in maintaining cortical neuron excitability may underlie the cortical activity alterations observed in Cntnap2−/− rats.

Mammalian hearing involves the mechanoelectrical transduction (MET) of sound-induced fluid waves in the cochlea. Essential to this process are the specialised sensory cochlear cells, the inner (IHCs) and outer hair cells (OHCs). While genetic hearing loss is highly heterogeneous, understanding the requirement of each gene will lead to a better understanding of the molecular basis of hearing and also to therapeutic opportunities for deafness. The Neuroplastin ( Nptn ) gene, which encodes two protein isoforms Np55 and Np65, is required for hearing, and homozygous loss-of-function mutations that affect both isoforms lead to profound deafness in mice. Here we have utilised several distinct mouse models to elaborate upon the spatial, temporal, and functional requirement of Nptn for hearing. While we demonstrate that both Np55 and Np65 are present in cochlear cells, characterisation of a Np65-specific mouse knockout shows normal hearing thresholds indicating that Np65 is functionally redundant for hearing. In contrast, we find that Nptn -knockout mice have significantly reduced maximal MET currents and MET channel open probabilities in mature OHCs, with both OHCs and IHCs also failing to develop fully mature basolateral currents. Furthermore, comparing the hearing thresholds and IHC synapse structure of Nptn- knockout mice with those of mice that lack Nptn only in IHCs and OHCs shows that the majority of the auditory deficit is explained by hair cell dysfunction, with abnormal afferent synapses contributing only a small proportion of the hearing loss. Finally, we show that continued expression of Neuroplastin in OHCs of adult mice is required for membrane localisation of Plasma Membrane Ca 2+ ATPase 2 (PMCA2), which is essential for hearing function. Moreover, Nptn haploinsufficiency phenocopies Atp2b2 (encodes PMCA2) mutations, with heterozygous Nptn -knockout mice exhibiting hearing loss through genetic interaction with the Cdh23 ahl allele. Together, our findings provide further insight to the functional requirement of Neuroplastin for mammalian hearing.

Cross-modal plasticity occurs when the function of remaining senses is enhanced following deprivation or loss of a sensory modality. Auditory neural responses are enhanced in the auditory cortex, including increased sensitivity and frequency selectivity, following short-term visual deprivation in adult mice (Petrus et al. Neuron 81:664-673, 2014). Whether or not these visual deprivation-induced neural changes translate into improved auditory perception and performance remains unclear. As an initial investigation of the effects of adult visual deprivation on auditory behaviors, CBA/CaJ mice underwent binocular enucleation at 3-4 weeks old and were tested on a battery of learned behavioral tasks, acoustic startle response (ASR), and prepulse inhibition (PPI) tests beginning at least 2 weeks after the enucleation procedure. Auditory brain stem responses (ABRs) were also measured to screen for potential effects of visual deprivation on non-behavioral hearing function. Control and enucleated mice showed similar tone detection sensitivity and frequency discrimination in a conditioned lick suppression test. Both groups showed normal reactivity to sound as measured by ASR in a quiet background. However, when startle-eliciting stimuli were presented in noise, enucleated mice showed decreased ASR amplitude relative to controls. Control and enucleated mice displayed no significant differences in ASR habituation, PPI tests, or ABR thresholds, or wave morphology. Our findings suggest that while adult-onset visual deprivation induces cross-modal plasticity at the synaptic and circuit levels, it does not substantially influence simple auditory behavioral performance.

Sound-level coding in the auditory nerve is achieved through the progressive recruitment of auditory nerve fibers (ANFs) that differ in threshold of activation and in the stimulus level at which the spike rate saturates. To investigate the functional state of the ANFs, the electrophysiological tests routinely used in clinics only capture the first action potentials firing in synchrony at the onset of the acoustic stimulation. Assessment of other properties (e.g., spontaneous rate and adaptation time constants) requires single-fiber recordings directly from the nerve, which for ethical reasons is not allowed in humans. By combining neuronal activity measurements at the round window and signal-processing algorithms, we constructed a peristimulus time response (PSTR), with a waveform similar to the peristimulus time histograms (PSTHs) derived from single-fiber recordings in young adult female gerbils. Simultaneous recordings of round-window PSTR and single-fiber PSTH provided models to predict the adaptation kinetics and spontaneous rate of the ANFs tuned at the PSTR probe frequency. The predictive model derived from gerbils was then validated in female mice and finally applied to humans by recording PSTRs from the auditory nerve in normal-hearing patients who underwent cerebellopontine angle surgeries. A rapid adaptation time constant of ∼3 ms and a mean spontaneous rate of ∼22 spikes/s in the 4 kHz frequency range were found. This study offers a promising diagnostic tool to map the human auditory nerve, thus opening new avenues to better understanding auditory neuropathies, tinnitus, and hyperacusis. SIGNIFICANCE STATEMENT Neural adaptation in auditory nerve fibers corresponds to the reduction in the neuronal activity to prolonged or repeated sound stimulation. For obvious ethical reasons, single-fiber recordings from the auditory nerve are not feasible in humans, creating a critical gap in extending data obtained using animal models to humans. Using electrocochleography in rodents, we inferred adaptation kinetics and spontaneous discharge rates of the auditory nerve fibers in humans. Routinely used in basic and clinical laboratories, this tool will provide a better understanding of auditory disorders such as neuropathies, tinnitus, and hyperacusis, and will help to improve hearing-aid fittings.

Research on children and adults with developmental dyslexia—a specific difficulty in learning to read and spell—suggests that phonological deficits in dyslexia are linked to basic auditory deficits in temporal sampling. However, it remains undetermined whether such deficits are already present in infancy, especially during the sensitive period when the auditory system specializes in native phoneme perception. Because dyslexia is strongly hereditary, it is possible to examine infants for early predictors of the condition before detectable symptoms emerge. This study examines low-level auditory temporal sampling in infants at risk for dyslexia across the sensitive period of native phoneme learning. Using magnetoencephalography (MEG), we found deficient auditory sampling at theta in at-risk infants at both 6 and 12 months, indicating atypical auditory sampling at the syllabic rate in those infants across the sensitive period for native-language phoneme learning. This interpretation is supported by our additional finding that auditory sampling at theta predicted later vocabulary comprehension, nonlinguistic communication and the ability to combine words. Our results indicate a possible early marker of risk for dyslexia.

Parkinson’s disease (PD), as a manifestation of basal ganglia dysfunction, is associated with a number of speech deficits, including reduced voice modulation and vocal output. Interestingly, previous work has shown that participants with PD show an increased feedback-driven motor response to unexpected fundamental frequency perturbations during speech production, and a heightened ability to detect differences in vocal pitch relative to control participants. Here, we explored one possible contributor to these enhanced responses. We recorded the frequency-following auditory brainstem response (FFR) to repetitions of the speech syllable [da] in PD and control participants. Participants with PD displayed a larger amplitude FFR related to the fundamental frequency of speech stimuli relative to the control group. The current preliminary results suggest the dysfunction of the basal ganglia in PD contributes to the early stage of auditory processing and may reflect one component of a broader sensorimotor processing impairment associated with the disease.

GJB2 and GJB6 are adjacent genes encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, with overlapping expressions in the inner ear. Both genes are associated with the commonest monogenic hearing disorder, recessive isolated deafness DFNB1. Cx26 plays an important role in auditory development, while the role of Cx30 in hearing remains controversial. Previous studies found that Cx30 knockout mice had severe hearing loss along with a 90% reduction in Cx26, while another Cx30 knockout mouse model showed normal hearing with nearly half of Cx26 preserved. In this study, we used CRISPR/Cas9 technology to establish a new Cx30 knockout mouse model (Cx30 −/− ), which preserves approximately 70% of Cx26. We found that the 1, 3, and 6-month-old Cx30 −/− mice showed mild hearing loss at full frequency. Immunofluorescence and HE staining suggested no significant differences in microstructure of the cochlea between Cx30 −/− mice and wild-type mice. However, transmission electron microscopy showed slight cavity-like damage in the stria vascularis of Cx30 −/− mice. And Cx30 deficiency reduced the production of endocochlear potential (EP) and the release of ATP, which may have induced hearing loss. Taken together, this study showed that lack of Cx30 can lead to hearing loss with an approximately 30% reduction of Cx26 in the present Cx30 knockout model. Hence, Cx30 may play an important rather than redundant role in hearing development.

Sensory hypersensitivity, especially in the auditory system, is a common symptom in Fragile X syndrome (FXS), the most common monogenic form of intellectual disability. However, linking phenotypes across genetic background strains of mouse models has been a challenge and could underly some of the issues with translatability of drug studies to the human condition. This study is the first to characterize the auditory brain stem response (ABR), a minimally invasive physiological readout of early auditory processing that is also used in humans, in a commonly used mouse background strain model of FXS, C57BL/6J. We measured morphological features of pinna and head and used ABR to measure the hearing range, and monaural and binaural auditory responses in hemizygous males, homozygous females, and heterozygous females compared with those in wild-type mice. Consistent with previous study, we showed no difference in morphological parameters across genotypes or sexes. There was no significant difference in hearing range between the sexes or genotypes, however there was a trend towards high frequency hearing loss in male FXS mice. In contrast, female mice with homozygous FXS had a decreased amplitude of wave IV of the monaural ABR, while there was no difference in males for amplitudes and no change in latency of ABR waveforms across sexes and genotypes. Finally, males with FXS had an increased latency of the binaural interaction component (BIC) at 0 interaural timing difference compared with that in wild-type males. These findings further clarify auditory brain stem processing in FXS by adding more information across genetic background strains allowing for a better understanding of shared phenotypes.

Voltage-gated Ca v Ca 2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the α 2 δ-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. α 2 δ-4 is prominently expressed in the retina and is crucial for vision, but extra-retinal functions of α 2 δ-4 have not been investigated. Here, we sought to fill this gap by analyzing the behavioral phenotypes of α 2 δ-4 knockout (KO) mice. α 2 δ-4 KO mice (both males and females) exhibited significant impairments in prepulse inhibition that were unlikely to result from the modestly elevated auditory brainstem response thresholds. Whereas α 2 δ-4 KO mice of both sexes were hyperactive in various assays, only females showed impaired motor learning/coordination in the rotarod assay. Female but not male α 2 δ-4 KO mice exhibited anxiolytic and anti-depressive behaviors in the elevated plus maze and tail suspension tests, respectively. Our results reveal an unexpected role for α 2 δ-4 in cognitive and motor function and identify α 2 δ-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.

Objectives: This study examined whether remote microphone (RM) systems improved listening-in-noise performance in youth with autism. We explored effects of RM system use on both listening-in-noise accuracy and listening effort in a well-characterized sample of participants with autism. We hypothesized that listening-in-noise accuracy would be enhanced and listening effort reduced, on average, when participants used the RM system. Furthermore, we predicted that effects of RM system use on listening-in-noise accuracy and listening effort would vary according to participant characteristics. Specifically, we hypothesized that participants who were chronologically older, had greater nonverbal cognitive and language ability, displayed fewer features of autism, and presented with more typical sensory and multisensory profiles might exhibit greater benefits of RM system use than participants who were younger, had less nonverbal cognitive or language ability, displayed more features of autism, and presented with greater sensory and multisensory disruptions. Design: We implemented a within-subjects design to investigate our hypotheses, wherein 32 youth with autism completed listening-in-noise testing with and without an RM system. Listening-in-noise accuracy and listening effort were evaluated simultaneously using a dual-task paradigm for stimuli varying in complexity (i.e., syllable-, word-, sentence-, and passage-level). In addition, several putative moderators of RM system effects (i.e., sensory and multisensory function, language, nonverbal cognition, and broader features of autism) on outcomes of interest were evaluated. Results: Overall, RM system use resulted in higher listening-in-noise accuracy in youth with autism compared with no RM system use. The observed benefits were all large in magnitude, although the benefits on average were greater for more complex stimuli (e.g., key words embedded in sentences) and relatively smaller for less complex stimuli (e.g., syllables). Notably, none of the putative moderators significantly influenced the effects of the RM system on listening-in-noise accuracy, indicating that RM system benefits did not vary according to any of the participant characteristics assessed. On average, RM system use did not have an effect on listening effort across all youth with autism compared with no RM system use but instead yielded effects that varied according to participant profile. Specifically, moderated effects indicated that RM system use was associated with increased listening effort for youth who had (a) average to below-average nonverbal cognitive ability, (b) below-average language ability, and (c) reduced audiovisual integration. RM system use was also associated with decreased listening effort for youth with very high nonverbal cognitive ability. Conclusions: This study extends prior work by showing that RM systems have the potential to boost listening-in-noise accuracy for youth with autism. However, this boost in accuracy was coupled with increased listening effort, as indexed by longer reaction times while using an RM system, for some youth with autism, perhaps suggesting greater engagement in the listening-in-noise tasks when using the RM system for youth who had lower cognitive abilities, were less linguistically able, and/or have difficulty integrating seen and heard speech. These findings have important implications for clinical practice, suggesting RM system use in classrooms could potentially improve listening-in-noise performance for some youth with autism.

Auditory function declines with age, as evidenced by communication difficulties in challenging listening environments for older adults. Declining auditory function may arise, in part, from an age-related loss and/or inactivity of low-spontaneous-rate (SR) auditory nerve (AN) fibers, a subgroup of neurons important for suprathreshold processing. Compared to high-SR fibers, low-SR fibers take longer to recover from prior stimulation. Taking advantage of this difference, the forward-masked recovery function paradigm estimates the relative proportions of low- and high-SR fibers in the AN by quantifying the time needed for AN responses to recover from prior stimulation (ΔTrecovery). Due to the slower recovery of low-SR fibers, ANs that need more time to fully recover (longer ΔTrecovery) are estimated to have a larger proportion of low-SR fibers than ANs that need less time (shorter ΔTrecovery). To test the hypothesis that low-SR fiber activity is reduced in older humans, the current study assessed recovery functions in 32 older and 16 younger adults using the compound action potential. Results show that ΔTrecovery is shorter for older adults than for younger adults, consistent with a theorized age-related loss and/or inactivity of low-SR fibers. ΔTrecovery did not differ between individuals with and without a prior history of noise exposure as assessed by self-report. This study is the first to successfully assess forward-masked recovery functions in both younger and older adults and provides important insights into the structural and functional changes occurring in the AN with increasing age.

Noise exposure causes noise-induced hearing loss (NIHL). NIHL exhibits loss of inner ear sensory hair cells and is often irreparable. Although oxidative stress is involved in hearing loss, the complex mechanisms involved in NIHL are unclear. Hypoxia-inducible factor 1α (HIF-1α) has been suggested to be essential for protecting sensory hair cells. Additionally, it has been shown that ROS is involved in modulating the stability of HIF-1α. To investigate the NIHL pathogenesis, we established a tert-butyl hydroperoxide (t-BHP)-induced oxidative stress damage model in hair-like HEI-OC1 cells and an NIHL model in C57BL/6 mice. Protein and mRNA expression were determined, and biochemical parameters including reactive oxygen species (ROS) accumulation, glucose uptake, adenosine triphosphat (ATP) production, and mitochondrial content were evaluated. In HEI-OC1 cells, t-BHP induced ROS accumulation and reduced mitochondrial content and oxygen consumption, but the ATP level was unaffected. Additionally, there was increased glucose uptake and lactate release along with elevated expression of HIF-1α, glucose transporter 1, and several glycolytic enzymes. Consistently, noise trauma induced oxidative stress and the expression of HIF-1α and glycolytic enzymes in mice. Thus, we concluded that ROS induced HIF-1α expression, which promoted glycolysis, suggesting a metabolic shift maintained the ATP level to attenuate hair cell damage in NIHL.

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.

Viral-mediated gene augmentation, silencing, or editing offers tremendous promise for the treatment of inherited and acquired deafness. Inner-ear gene therapies often require a safe, clinically useable and effective route of administration to target both ears, while avoiding damage to the delicate structures of the inner ear. Here, we examined the possibility of using a cisterna magna injection as a new cochlear local route for initiating binaural transduction by different serotypes of the adeno-associated virus (AAV2/8, AAV2/9, AAV2/Anc80L65). The results were compared with those following canalostomy injection, one of the existing standard inner ear local delivery routes. Our results demonstrated that a single injection of AAVs enables high-efficiency binaural transduction of almost all inner hair cells with a basal-apical pattern and of large numbers of spiral ganglion neurons of the basal portion of the cochlea, without affecting auditory function and cochlear structures. Taken together, these results reveal the potential for using a cisterna magna injection as a local route for binaural gene therapy applications, but extensive testing will be required before translation beyond mouse models.

Objectives: Listening effort is needed to understand speech that is degraded by hearing loss, a noisy environment, or both. This in turn reduces cognitive spare capacity, the amount of cognitive resources available for allocation to concurrent tasks. Predictive sentence context enables older listeners to perceive speech more accurately, but how does contextual information affect older adults’ listening effort? The current study examines the impacts of sentence context and cognitive (memory) load on sequential dual-task behavioral performance in older adults. To assess whether effects of context and memory load differ as a function of older listeners’ hearing status, baseline working memory capacity, or both, effects were compared across separate groups of participants with and without hearing loss and with high and low working memory capacity. Design: Participants were older adults (age 60–84 years; n = 63) who passed a screen for cognitive impairment. A median split classified participants into groups with high and low working memory capacity. On each trial, participants listened to spoken sentences in noise and reported sentence-final words that were either predictable or unpredictable based on sentence context, and also recalled short (low-load) or long (high-load) sequences of digits that were presented visually before each spoken sentence. Speech intelligibility was quantified as word identification accuracy, and measures of listening effort included digit recall accuracy, and response time to words and digits. Correlations of context benefit in each dependent measure with working memory and vocabulary were also examined. Results: Across all participant groups, accuracy and response time for both word identification and digit recall were facilitated by predictive context, indicating that in addition to an improvement in intelligibility, listening effort was also reduced when sentence-final words were predictable. Effects of predictability on all listening effort measures were observed whether or not trials with an incorrect word identification response were excluded, indicating that the effects of predictability on listening effort did not depend on speech intelligibility. In addition, although cognitive load did not affect word identification accuracy, response time for word identification and digit recall, as well as accuracy for digit recall, were impaired under the high-load condition, indicating that cognitive load reduced the amount of cognitive resources available for speech processing. Context benefit in speech intelligibility was positively correlated with vocabulary. However, context benefit was not related to working memory capacity. Conclusions: Predictive sentence context reduces listening effort in cognitively healthy older adults resulting in greater cognitive spare capacity available for other mental tasks, irrespective of the presence or absence of hearing loss and baseline working memory capacity.

Listeners with sensorineural hearing loss (SNHL) struggle to understand speech, especially in noise, despite audibility compensation. These real-world suprathreshold deficits are hypothesized to arise from degraded frequency tuning and reduced temporal-coding precision; however, peripheral neurophysiological studies testing these hypotheses have been largely limited to in-quiet artificial vowels. Here, we measured single auditory-nerve-fiber responses to a connected speech sentence in noise from anesthetized male chinchillas with normal hearing (NH) or noise-induced hearing loss (NIHL). Our results demonstrated that temporal precision was not degraded following acoustic trauma, and furthermore that sharpness of cochlear frequency tuning was not the major factor affecting impaired peripheral coding of connected speech in noise. Rather, the loss of cochlear tonotopy, a hallmark of NH, contributed the most to both consonant-coding and vowel-coding degradations. Because distorted tonotopy varies in degree across etiologies (e.g., noise exposure, age), these results have important implications for understanding and treating individual differences in speech perception for people suffering from SNHL. SIGNIFICANCE STATEMENT Difficulty understanding speech in noise is the primary complaint in audiology clinics and can leave people with sensorineural hearing loss (SNHL) suffering from communication difficulties that affect their professional, social, and family lives, as well as their mental health. We measured single-neuron responses from a preclinical SNHL animal model to characterize salient neural-coding deficits for naturally spoken speech in noise. We found the major mechanism affecting neural coding was not a commonly assumed factor, but rather a disruption of tonotopicity, the systematic mapping of acoustic frequency to cochlear place that is a hallmark of normal hearing. Because the degree of distorted tonotopy varies across hearing-loss etiologies, these results have important implications for precision audiology approaches to diagnosis and treatment of SNHL.