Auditory Research publications

Handling (H) and cross-fostering (CF) rodent pups during postnatal development triggers changes in maternal behavior which in turn trigger long-term physiological changes in the offspring. However, less is known about the short-term effects of H and CF on infant development. In this study we hypothesized that manipulations of maternal care affect the onset of hearing in Wistar rats. To test this hypothesis we obtained auditory brainstem responses (ABRs) and micro-CT x-ray scans to measure changes in the development of the auditory periphery in H and CF pups manipulated at postnatal day (P)1, P5, or P9. We found evidence of changes in hearing development in H and CF pups compared with naive pups, including changes in the percentage of animals with ABRs during development, a decrease in ABR thresholds between P13 and P15, and anatomical results consistent with an accelerated formation of the middle ear cavity and opening of the ear canal. Biochemical measurements showed elevated levels of thyroid hormone in plasma from naive and CF pups. These results provide evidence that manipulations of maternal care accelerate hearing onset in Wistar rats. Understanding the mechanisms by which maternal care affects hearing onset opens new opportunities to study experience-dependent development of mammalian hearing.

Auditory processing disorder (APD) is defined as a processing deficit in the auditory modality and spans multiple processes. To date, APD diagnosis is mostly based on the utilization of speech material. Adequate nonspeech tests that allow differentiation between an actual central hearing disorder and related disorders such as specific language impairments are still not adequately available. In the present study, 84 children between 6 and 17 years of age (clinical group), referred to three audiological centers for APD diagnosis, were evaluated with standard audiological tests and additional auditory discrimination tests. Latter tests assessed the processing of basic acoustic features at two different stages of the ascending central auditory system: (1) auditory brainstem processing was evaluated by quantifying interaural frequency, level, and signal duration discrimination (interaural tests). (2) Diencephalic/telencephalic processing was assessed by varying the same acoustic parameters (plus signals with sinusoidal amplitude modulation), but presenting the test signals in conjunction with noise pulses to the contralateral ear (dichotic(signal/noise) tests). Data of children in the clinical group were referenced to normative data obtained from more than 300 normally developing healthy school children. The results in the audiological and the discrimination tests diverged widely. Of the 39 children that were diagnosed with APD in the audiological clinic, 30 had deficits in auditory performance. Even more alarming was the fact that of the 45 children with a negative APD diagnosis, 32 showed clear signs of a central hearing deficit. Based on these results, we suggest revising current diagnostic procedure to evaluate APD in order to more clearly differentiate between central auditory processing deficits and higher-order (cognitive and/or language) processing deficits.

The activation of the ventral tegmental area (VTA) can rebuild the tonotopic representation in the primary auditory cortex (A1), but the cellular mechanisms remain largely unknown. Here, we investigated the firing patterns and membrane potential dynamics of neurons in A1 under the influence of VTA activation using in vivo intracellular recording. We found that VTA activation can significantly reduce the variability of sound evoked responses and promote the firing precision and strength of A1 neurons. Furthermore, the compressed response window was caused by an early hyperpolarization as a result of enhanced circuit inhibition. Our study suggested a possible mechanism of how the reward system affects information processing in sensory cortex: VTA activation strengthens cortical inhibition, which shortens the response window of post-synaptic cortical neurons and further promotes the precision and strength of neuronal activity.

Selective auditory attention causes a relative enhancement of the neural representation of important information and suppression of the neural representation of distracting sound, which enables a listener to analyze and interpret information of interest. Some studies suggest that in both vision and in audition, the "unit" on which attention operates is an object: an estimate of the information coming from a particular external source out in the world. In this view, which object ends up in the attentional foreground depends on the interplay of top-down, volitional attention and stimulus-driven, involuntary attention. Here, we test the idea that auditory attention is object based by exploring whether continuity of a non-spatial feature (talker identity, a feature that helps acoustic elements bind into one perceptual object) also influences selective attention performance. In Experiment 1, we show that perceptual continuity of target talker voice helps listeners report a sequence of spoken target digits embedded in competing reversed digits spoken by different talkers. In Experiment 2, we provide evidence that this benefit of voice continuity is obligatory and automatic, as if voice continuity biases listeners by making it easier to focus on a subsequent target digit when it is perceptually linked to what was already in the attentional foreground. Our results support the idea that feature continuity enhances streaming automatically, thereby influencing the dynamic processes that allow listeners to successfully attend to objects through time in the cacophony that assails our ears in many everyday settings.

Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG) expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc) and the early growth response gene-1 (Egr-1), appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS) paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC) and auditory cortex (AC), in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B) was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus.

Animals often listen selectively for particular sounds, a strategy that could alter neural encoding mechanisms to maximize the ability to detect the target. Here, we recorded auditory cortex neuron responses in well trained, freely moving gerbils as they performed a tone detection task. Each trial was initiated by the animal, providing a predictable time window during which to listen. No sound was presented on nogo trials, permitting us to assess spontaneous activity on trials in which a signal could have been expected, but was not delivered. Immediately after animals initiated a trial, auditory cortex neurons displayed a 26% reduction in spontaneous activity. Moreover, when stimulus-driven discharge rate was referenced to this reduced baseline, a larger fraction of auditory cortex neurons displayed a detection threshold within 10 dB of the behavioral threshold. These findings suggest that auditory cortex spontaneous discharge rate can be modulated transiently during task performance, thereby increasing the signal-to-noise ratio and enhancing signal detection.

The localization of high-frequency sounds in the horizontal plane uses an interaural-level difference (ILD) cue, yet little is known about the synaptic mechanisms that underlie processing this cue in the inferior colliculus (IC) of mouse. Here, we study the synaptic currents that process ILD in vivo and use stimuli in which ILD varies around a constant average binaural level (ABL) to approximate sounds on the horizontal plane. Monaural stimulation in either ear produced EPSCs and IPSCs in most neurons. The temporal properties of monaural responses were well matched, suggesting connected functional zones with matched inputs. The EPSCs had three patterns in response to ABL stimuli, preference for the sound field with the highest level stimulus: (1) contralateral; (2) bilateral highly lateralized; or (3) at the center near 0 ILD. EPSCs and IPSCs were well correlated except in center-preferred neurons. Summation of the monaural EPSCs predicted the binaural excitatory response but less well than the summation of monaural IPSCs. Binaural EPSCs often showed a nonlinearity that strengthened the response to specific ILDs. Extracellular spike and intracellular current recordings from the same neuron showed that the ILD tuning of the spikes was sharper than that of the EPSCs. Thus, in the IC, balanced excitatory and inhibitory inputs may be a general feature of synaptic coding for many types of sound processing.

Age-related hearing loss (ARHL) is one of the most frequent sensory impairments in senescence and is a source of important socio-economic consequences. Understanding the pathological responses that occur in the central auditory pathway of patients who suffer from this disability is vital to improve its diagnosis and treatment. Therefore, the goal of this study was to characterize age-related modifications in auditory brainstem responses (ABR) and to determine whether these functional responses might be accompanied by an imbalance between excitation and inhibition in the cochlear nucleus of Wistar rats. To do so, ABR recordings at different frequencies and immunohistochemistry for the vesicular glutamate transporter 1 (VGLUT1) and the vesicular GABA transporter (VGAT) in the ventral cochlear nucleus (VCN) were performed in young, middle-aged and old male Wistar rats. The results demonstrate that there was a significant increase in the auditory thresholds, a significant decrease in the amplitudes and an increase in the latencies of the ABR waves as the age of the rat increased. Additionally, there were decreases in VGLUT1 and VGAT immunostaining in the VCN of older rats compared to younger rats. Therefore, the observed age-related decline in the magnitude of auditory evoked responses might be due in part to a reduction in markers of excitatory function; meanwhile, the concomitant reduction in both excitatory and inhibitory markers might reflect a common central alteration in animal models of ARLH. Together, these findings highlight the suitability of the Wistar rat as an excellent model to study ARHL.

The neural substrate for the perception of vocalizations is relatively well described, but how their timing and specificity are tightly coupled with accompanying physiological changes and context-appropriate behaviors remains unresolved. We hypothesized that temporally integrated vocal and emotive responses, especially the expression of fear, vigilance and aggression, originate within the amygdala. To test this hypothesis, we performed electrical microstimulation at 461 highly restricted loci within the basal and central amygdala in awake mustached bats. At a subset of these sites, high frequency stimulation with weak constant current pulses presented at near-threshold levels triggered vocalization of either echolocation pulses or social calls. At the vast majority of locations, microstimulation produced a constellation of changes in autonomic and somatomotor outputs. These changes included widespread co-activation of significant tachycardia and hyperventilation and/or rhythmic ear pinna movements (PMs). In a few locations, responses were constrained to vocalization and/or PMs despite increases in the intensity of stimulation. The probability of eliciting echolocation pulses vs. social calls decreased in a medial-posterior to anterolateral direction within the centrobasal amygdala. Microinjections of kainic acid (KA) at stimulation sites confirmed the contribution of cellular activity rather than fibers-of-passage in the control of multimodal outputs. The results suggest that localized clusters of neurons may simultaneously modulate the activity of multiple central pattern generators (CPGs) present within the brainstem.

Gentamicin is an aminoglycoside antibiotic used to treat gram-negative bacterial infections. Treatment with this antibiotic carries the potential for adverse side effects, including ototoxicity and nephrotoxicity. Ototoxic effects are at least in part a consequence of oxidative stress, and various antioxidants have been used to attenuate gentamicin-induced hair cell death and hearing loss. Here, a combination of nutrients previously shown to reduce oxidative stress in the hair cells and attenuate hearing loss after other insults was evaluated for potential protection against gentamicin-induced ototoxicity. Guinea pigs were maintained on a nutritionally complete standard laboratory animal diet or a diet supplemented with β-carotene, vitamins C and E, and magnesium. Three diets with iterative increases in nutrient levels were screened; the final diet selected for study use was one that produced statistically reliable increases in plasma levels of vitamins C and E and magnesium. In two separate studies, significant decreases in gentamicin-induced hearing loss at frequencies including 12 kHz and below were observed, with less benefit at the higher frequencies. Consistent with the functional protection, robust protection of both the inner and outer hair cell populations was observed, with protection largely in the upper half of the cochlea. Protection was independently assessed in two different laboratories, using two different strains of guinea pigs. Additional in vitro tests did not reveal any decrease in antimicrobial activity with nutrient additives. Currently, there are no FDA-approved treatments for the prevention of gentamicin-induced ototoxicity. The current data provide a rationale for continued investigations regarding translation to human patients.

Purpose The use of bilateral stimulation is becoming common for cochlear implant (CI) recipients with either (a) a CI in one ear and a hearing aid (HA) in the nonimplanted ear (CI&HA—bimodal) or (b) CIs in both ears (CI&CI—bilateral). The objective of this study was to evaluate 4 individuals who transitioned from bimodal to bilateral stimulation. Method Participants had completed a larger study of bimodal hearing and subsequently received a second CI. Test procedures from the bimodal study, including roaming speech recognition, localization, and a questionnaire (the Speech, Spatial, and Qualities of Hearing Scale; Gatehouse & Noble, 2004) were repeated after 6–7 months of bilateral CI experience. Results Speech recognition and localization were not significantly different between bimodal and unilateral CI. In contrast, performance was significantly better with CI&CI compared with unilateral CI. Speech recognition with CI&CI was significantly better than with CI&HA for 2 of 4 participants. Localization was significantly better for all participants with CI&CI compared with CI&HA. CI&CI performance was rated as significantly better on the Speech, Spatial, and Qualities of Hearing Scale compared with CI&HA. Conclusions There was a strong preference for CI&CI for all participants. The variability in speech recognition and localization, however, suggests that performance under these stimulus conditions is individualized. Differences in hearing and/or HA history may explain performance differences.

Although many studies have examined the precedence effect (PE), few have tested whether it shows a buildup and breakdown in nonhuman animals comparable to that seen in humans. These processes are thought to reflect the ability of the auditory system to adjust to a listener's acoustic environment, and their mechanisms are still poorly understood. In this study, ferrets were trained on a two-alternative forced-choice task to discriminate the azimuthal direction of brief sounds. In one experiment, pairs of noise bursts were presented from two loudspeakers at different interstimulus delays (ISDs). Results showed that localization performance changed as a function of ISD in a manner consistent with the PE being operative. A second experiment investigated buildup and breakdown of the PE by measuring the ability of ferrets to discriminate the direction of a click pair following presentation of a conditioning train. Human listeners were also tested using this paradigm. In both species, performance was better when the test clicks and conditioning train had the same ISD but deteriorated following a switch in the direction of the leading and lagging sounds between the conditioning train and test clicks. These results suggest that ferrets, like humans, experience a buildup and breakdown of the PE.

Purpose In this study, the authors examined the effects of aging and residual hearing on the identification of acoustically similar and dissimilar vowels in adults with postlingual deafness who use hearing aids (HAs) and/or cochlear implants (CIs). Method The authors used two groups of acoustically similar and dissimilar vowels to assess vowel identification. Also, the Consonant–Nucleus–Consonant Word Recognition Test (Peterson & Lehiste, 1962) and sentences from the Hearing in Noise Test (Nilsson, Soli, & Sullivan, 1994) were administered. Forty CI recipients with postlingual deafness (ages 31–81 years) participated in the study. Results Acoustically similar vowels were more difficult to identify than acoustically dissimilar vowels. With increasing age, performance deteriorated when identifying acoustically similar vowels. Vowel identification was also affected by the use of a contralateral HA and the degree of residual hearing prior to implantation. Moderate correlations were found between speech perception and vowel identification performance. Conclusions Identification performance was affected by the acoustic similarity of the vowels. Older adults experienced more difficulty identifying acoustically similar confusable vowels than did younger adults. The findings might lend support to the ease of language understanding model (Ronnberg, Rudner, Foo, & Lunner, 2008), which proposes that the quality and perceptual robustness of acoustic input affects speech perception. Supplemental Material https://doi.org/10.23641/asha.6170174

Mutations in the connexin 26 gene (GJB2) are the most common genetic cause of deafness, leading to congenital bilateral non-syndromic sensorineural hearing loss. Here we report the generation of a mouse model for a connexin 26 (Cx26) mutation, in which cre-Sox10 drives excision of the Cx26 gene from non-sensory cells flanking the auditory epithelium. We determined that these conditional knockout mice, designated Gjb2-CKO, have a severe hearing loss. Immunocytochemistry of the auditory epithelium confirmed absence of Cx26 in the non-sensory cells. Histology of the organ of Corti and the spiral ganglion neurons (SGNs) performed at ages 1, 3, or 6 months revealed that in Gjb2-CKO mice, the organ of Corti began to degenerate in the basal cochlear turn at an early stage, and the degeneration rapidly spread to the apex. In addition, the density of SGNs in Rosenthal's canal decreased rapidly along a gradient from the base of the cochlea to the apex, where some SGNs survived until at least 6 months of age. Surviving neurons often clustered together and formed clumps of cells in the canal. We then assessed the influence of brain derived neurotrophic factor (BDNF) gene therapy on the SGNs of Gjb2-CKO mice by inoculating Adenovirus with the BDNF gene insert (Ad.BDNF) into the base of the cochlea via the scala tympani or scala media. We determined that over-expression of BDNF beginning around 1 month of age resulted in a significant rescue of neurons in Rosenthal's canal of the cochlear basal turn but not in the middle or apical portions. This data may be used to design therapies for enhancing the SGN physiological status in all GJB2 patients and especially in a sub-group of GJB2 patients where the hearing loss progresses due to ongoing degeneration of the auditory nerve, thereby improving the outcome of cochlear implant therapy in these ears.

Cochlear implant electrical stimulation of the auditory system to rehabilitate deafness has been remarkably successful. Its deployment requires both an intact auditory nerve and a suitably patent cochlear lumen. When disease renders prerequisite conditions impassable, such as in neurofibromatosis type II and cochlear obliterans, alternative treatment targets are considered. Electrical stimulation of the cochlear nucleus and midbrain in humans has delivered encouraging clinical outcomes, buttressing the promise of central auditory prostheses to mitigate deafness in those who are not candidates for cochlear implantation. In this study we explored another possible implant target: the auditory thalamus. In anesthetized cats, we first presented pure tones to determine frequency preferences of thalamic and cortical sites. We then electrically stimulated tonotopically organized thalamic sites while recording from primary auditory cortical sites using a multichannel recording probe. Cathode-leading biphasic thalamic stimulation thresholds that evoked cortical responses were much lower than published accounts of cochlear and midbrain stimulation. Cortical activation dynamic ranges were similar to those reported for cochlear stimulation, but they were narrower than those found through midbrain stimulation. Our results imply that thalamic stimulation can activate auditory cortex at low electrical current levels and suggest an auditory thalamic implant may be a viable central auditory prosthesis.

Age-related hearing loss - presbycusis - is the number one neurodegenerative disorder and top communication deficit of our aged population. Like many aging disorders of the nervous system, damage from free radicals linked to production of reactive oxygen and/or nitrogen species (ROS and RNS, respectively) may play key roles in disease progression. The efficacy of the antioxidant systems, e.g., glutathione and thioredoxin, is an important factor in pathophysiology of the aging nervous system. In this investigation, relations between the expression of antioxidant-related genes in the auditory portion of the inner ear - cochlea, and age-related hearing loss was explored for CBA/CaJ mice. Forty mice were classified into four groups according to age and degree of hearing loss. Cochlear mRNA samples were collected and cDNA generated. Using Affymetrix® GeneChip, the expressions of 56 antioxidant-related gene probes were analyzed to estimate the differences in gene expression between the four subject groups. The expression of Glutathione peroxidase 6, Gpx6; Thioredoxin reductase 1, Txnrd1; Isocitrate dehydrogenase 1, Idh1; and Heat shock protein 1, Hspb1; were significantly different, or showed large fold-change differences between subject groups. The Gpx6, Txnrd1 and Hspb1 gene expression changes were validated using qPCR. The Gpx6 gene was upregulated while the Txnrd1 gene was downregulated with age/hearing loss. The Hspb1 gene was found to be downregulated in middle-aged animals as well as those with mild presbycusis, whereas it was upregulated in those with severe presbycusis. These results facilitate development of future interventions to predict, prevent or slow down the progression of presbycusis.

Stimulus-specific adaptation (SSA) is the reduction in response to a common stimulus that does not generalize, or only partially generalizes, to rare stimuli. SSA is strong and widespread in primary auditory cortex (A1) of rats, but is weak or absent in the main input station to A1, the ventral division of the medial geniculate body. To study SSA in A1, we recorded neural activity in A1 intracellularly using sharp electrodes. We studied the responses to tone pips of the same frequency in different contexts: as Standard and Deviants in Oddball sequences; in equiprobable sequences; in sequences consisting of rare tone presentations; and in sequences composed of many different frequencies, each of which was rare. SSA was found both in subthreshold membrane potential fluctuations and in spiking responses of A1 neurons. SSA for changes in frequency was large at a frequency difference of 44% between Standard and Deviant, and clearly present with tones separated by as little as 4%, near the behavioral frequency difference limen in rats. When using equivalent measures, SSA in spiking responses was generally larger than the SSA at the level of the membrane potential. This effect can be traced to the nonlinearity of the transformation between membrane potential to spikes. Using the responses to the same tone in different contexts made it possible to demonstrate that cortical SSA could not be fully explained by adaptation in narrow frequency channels, even at the level of the membrane potential. We conclude that local processing significantly contributes to the generation of cortical SSA.

Objective: Prevention of temporary threshold shift (TTS) after laboratory-based exposure to pure-tones, broadband noise, and narrowband noise signals has been achieved, but prevention of TTS under these experimental conditions may not accurately reflect protection against hearing loss following impulse noise. This study used a controlled laboratory-based TTS paradigm that incorporated impulsive stimuli into the exposure protocol; development of this model could provide a novel platform for assessing proposed therapeutics. Design: Participants played a video game that delivered gunfire-like sound through headphones as part of a target practice game. Effects were measured using audiometric threshold evaluations and distortion product otoacoustic emissions (DPOAEs). The sound level and number of impulses presented were sequentially increased throughout the study. Study sample: Participants were normal-hearing students at the University of Florida who provided written informed consent prior to participation. Results: TTS was not reliably induced by any of the exposure conditions assessed here. However, there was significant individual variability, and a subset of subjects showed TTS under some exposure conditions. Conclusions: A subset of participants demonstrated reliable threshold shifts under some conditions. Additional experiments are needed to better understand and optimize stimulus parameters that influence TTS after simulated impulse noise.

Auditory Scene Analysis provides a useful framework for understanding atypical auditory perception in autism. Specifically, a failure to segregate the incoming acoustic energy into distinct auditory objects might explain the aversive reaction autistic individuals have to certain auditory stimuli or environments. Previous research with non-autistic participants has demonstrated the presence of an Object Related Negativity (ORN) in the auditory event related potential that indexes pre-attentive processes associated with auditory scene analysis. Also evident is a later P400 component that is attention dependent and thought to be related to decision-making about auditory objects. We sought to determine whether there are differences between individuals with and without autism in the levels of processing indexed by these components. Electroencephalography (EEG) was used to measure brain responses from a group of 16 autistic adults, and 16 age- and verbal-IQ-matched typically-developing adults. Auditory responses were elicited using lateralized dichotic pitch stimuli in which inter-aural timing differences create the illusory perception of a pitch that is spatially separated from a carrier noise stimulus. As in previous studies, control participants produced an ORN in response to the pitch stimuli. However, this component was significantly reduced in the participants with autism. In contrast, processing differences were not observed between the groups at the attention-dependent level (P400). These findings suggest that autistic individuals have difficulty segregating auditory stimuli into distinct auditory objects, and that this difficulty arises at an early pre-attentive level of processing.

Besides the rapid fluctuations in pressure that constitute the “fine structure” of a sound stimulus, slower fluctuations in the sound's envelope represent an important temporal feature. At various stages in the auditory system, neurons exhibit tuning to envelope frequency and have been described as modulation filters. We examine such tuning in the ventral nucleus of the lateral lemniscus (VNLL) of the pentobarbital-anesthetized cat. The VNLL is a large but poorly accessible auditory structure that provides a massive inhibitory input to the inferior colliculus. We test whether envelope filtering effectively applies to the envelope spectrum when multiple envelope components are simultaneously present. We find two broad classes of response with often complementary properties. The firing rate of onset neurons is tuned to a band of modulation frequencies, over which they also synchronize strongly to the envelope waveform. Although most sustained neurons show little firing rate dependence on modulation frequency, some of them are weakly tuned. The latter neurons are usually band-pass or low-pass tuned in synchronization, and a reverse-correlation approach demonstrates that their modulation tuning is preserved to nonperiodic, noisy envelope modulations of a tonal carrier. Modulation tuning to this type of stimulus is weaker for onset neurons. In response to broadband noise, sustained and onset neurons tend to filter out envelope components over a frequency range consistent with their modulation tuning to periodically modulated tones. The results support a role for VNLL in providing temporal reference signals to the auditory midbrain.