ABR/DPOAE publications

Evaluation of patients who are unable to provide behavioral responses on standard clinical measures is challenging due to the lack of standard objective (non-behavioral) clinical audiological measures that assess the outcome of an intervention (e.g., hearing aids). Brainstem responses to short consonant-vowel stimuli (speech-auditory brainstem responses [speech-ABRs]) have been proposed as a measure of subcortical encoding of speech, speech detection, and speech-in-noise performance in individuals with normal hearing. Here, we investigated the potential application of speech-ABRs as an objective clinical outcome measure of speech detection, speech-in-noise detection and recognition, and self-reported speech understanding in 98 adults with sensorineural hearing loss. We compared aided and unaided speech-ABRs, and speech-ABRs in quiet and in noise. In addition, we evaluated whether speech-ABR F0 encoding (obtained from the complex cross-correlation with the 40 ms [da] fundamental waveform) predicted aided behavioral speech recognition in noise or aided self-reported speech understanding. Results showed that (a) aided speech-ABRs had earlier peak latencies, larger peak amplitudes, and larger F0 encoding amplitudes compared to unaided speech-ABRs; (b) the addition of background noise resulted in later F0 encoding latencies but did not have an effect on peak latencies and amplitudes or on F0 encoding amplitudes; and (c) speech-ABRs were not a significant predictor of any of the behavioral or self-report measures. These results show that speech-ABR F0 encoding is not a good predictor of speech-in-noise recognition or self-reported speech understanding with hearing aids. However, our results suggest that speech-ABRs may have potential for clinical application as an objective measure of speech detection with hearing aids.

Introduction: There are several key differences between impulse and continuous noise: the nature of the noise itself, the cochlear and neuronal structures affected, the severity to which they damage the auditory system, and the period of time in which damage occurs. Notably, no work on hidden hearing loss after impulse noise exposure has been done to this point, though it has been extensively studied after continuous noise. Hidden hearing loss manifests physiologically with reductions in suprathreshold amplitudes of the first wave of the auditory brainstem response, while auditory thresholds can remain relatively normal. Objective: This study aimed to assess the extent to which, if at all, hidden hearing loss is present after exposure to impulse noise in C57BL6/J mice. Methods: Thirty-one C57BL6/J mice were used in the experiment, in accordance with IACUC protocols. Auditory brainstem responses were recorded before and after noise exposures. The noise exposures consisted of 500 impulses at 137 dB peSPL. Results: Suprathreshold amplitude reductions in the P1 wave of the mouse auditory brainstem response were seen, but only at frequencies with significant threshold shift. Conclusion: These amplitude changes were consistent with hidden hearing loss, and we conclude that impulse noise can cause hidden hearing loss, but future studies are required to determine the specific mechanisms involved and if they parallel those of hidden hearing loss after continuous noise.

The medial olivocochlear reflex (MOCR) has been implicated in several auditory processes. The putative role of the MOCR in improving speech perception in noise is particularly relevant for children who complain of listening difficulties (LiD). The hypothesis that the MOCR may be impaired in individuals with LiD or auditory processing disorder has led to several investigations but without consensus. In two related studies, we compared the MOCR functioning of children with LiD and typically developing (TD) children in the same age range (7–17 years). In Study 1, we investigated ipsilateral, contralateral, and bilateral MOCR using forward-masked click-evoked otoacoustic emissions (CEOAEs; n = 17 TD, 17 LiD). In Study 2, we employed three OAE types: CEOAEs ( n = 16 TD, 21 LiD), stimulus frequency OAEs ( n = 21 TD, 30 LiD), and distortion product OAEs ( n = 17 TD, 22 LiD) in a contralateral noise paradigm. Results from both studies suggest that the MOCR functioning is not significantly different between the two groups. Some likely reasons for differences in findings among published studies could stem from the lack of strict data quality measures (e.g., high signal-to-noise ratio, control for the middle ear muscle reflex) that were enforced in the present study. The inherent variability of the MOCR, the subpar reliability of current MOCR methods, and the heterogeneity in auditory processing deficits that underlie auditory processing disorder make detecting clinically relevant differences in MOCR function impractical using current methods.

Introduction: To detect congenital hearing loss in mice, an objective measure is needed other than mouse behavioral observation. This study aimed to refine the methodology of auditory brainstem response measurement and identify potential congenital hearing loss models in laboratory mouse strains. Methods: Mice were anesthetized and fitted with head electrodes. Each mouse underwent four ABR measurements according to four testing conditions: A - no chamber; conventional tone; B - chamber; conventional tone; C - no chamber; short tone; D - chamber; short tone. Potential congenital hearing loss models were identified using 10 mice from each strain (C57BL, BALB/c, CH3, ICR, and ddY) through sound-attenuated ABR measurements with short-tone bursts. Potential congenital hearing loss models exhibited hearing thresholds ≥30 dB in both ears. Data were analyzed for normal distribution and variance homogeneity using the D'Agostino-Pearson/Kolmogorov-Smirnov and F value tests, respectively. One-way analysis of variance (ANOVA), with the Tukey-Kramer test, was used to conduct parametric analysis, and the Kruskal-Wallis/Friedman test, with a Dunn's test for post hoc analysis, was used to perform non-parametric analysis. Results: The simultaneous use of a sound-attenuating chamber and short-tone bursts provided clearly defined wave patterns, even at lower sound intensities. Inbred strains, especially C57BL/6 sub-strains, constitute suitable congenital hearing loss models. Conclusions: Our study shows that environmental factors should be addressed in animal studies of hearing function. Potential congenital hearing loss models may be found amongst commercially available inbred strains.

Rationale: Mutations of SLC26A4 that abrogate pendrin, expressed in endolymphatic sac, cochlea and vestibule, are known to cause autosomal recessive sensorineural hearing loss with enlargement of the membranous labyrinth. This is the first study to demonstrate the feasibility of gene therapy for pendrin-related hearing loss. Methods: We used a recombinant viral vector to transfect Slc26a4 cDNA into embryonic day 12.5 otocysts of pendrin-deficient knock-out (Slc26a4∆/∆ ) and pendrin-deficient knock-in (Slc26a4tm1Dontuh/tm1Dontuh ) mice. Results: Local gene-delivery resulted in spatially and temporally limited pendrin expression, prevented enlargement, failed to restore vestibular function, but succeeded in the restoration of hearing. Restored hearing phenotypes included normal hearing as well as sudden, fluctuating, and progressive hearing loss. Conclusion: Our study illustrates the feasibility of gene therapy for pendrin-related hearing loss, suggests differences in the requirement of pendrin between the cochlea and the vestibular labyrinth, and documents that insufficient pendrin expression during late embryonal and early postnatal development of the inner ear can cause sudden, fluctuating and progressive hearing loss without obligatory enlargement of the membranous labyrinth.

The Dach1 gene is expressed in the inner ear of normal mouse embryos in the area that differentiates into the cochlear stria vascularis (SV). We hypothesized that Dach1 downregulation in the inner ear would lead to SV dysplasia. However, because Dach1 knockout is embryonic lethal in mice, the role of Dach1 in the inner ear is unclear. , Here, we established inner ear-specific Dach1-knockdown mice and showed that Dach1 downregulation resulted in hearing loss, reduced endocochlear potential, and secondary outer hair cell loss. There were no abnormalities in marginal cells and basal cells in the SV or spiral ligament in inner ear-specific Dach1-knockdown mature mice. However, intermediate cell dysplasia and thinning of the SV were observed. Moreover, dynamic changes in the expression of key genes related to the epithelial-mesenchymal transition were observed in the lateral wall of the cochlear epithelium, which differentiated into the SV in inner ear-specific Dach1-knockdown mice at embryonic stages. In summary, suppression of Dach1 expression in the inner ear caused the epithelial-mesenchymal transition in the lateral wall of cochlear epithelium, resulting in loss of intermediate cells in the SV and SV dysplasia.

The microRNA (miR)-183/96/182 cluster plays important roles in the development and functions of sensory organs, including the inner ear. Point-mutations in the seed sequence of miR-96 result in non-syndromic hearing loss in both mice and humans. However, the lack of a functionally null mutant has hampered the evaluation of the cluster’s physiological functions. Here we have characterized a loss-of-function mutant mouse model (miR-183C GT/GT ), in which the miR-183/96/182 cluster gene is inactivated by a gene-trap (GT) construct. The homozygous mutant mice show profound congenital hearing loss with severe defects in cochlear hair cell (HC) maturation, alignment, hair bundle formation and the checkboard-like pattern of the cochlear sensory epithelia. The stereociliary bundles retain an immature appearance throughout the cochlea at postnatal day (P) 3 and degenerate soon after. The organ of Corti of mutant newborn mice has no functional mechanoelectrical transduction. Several predicted target genes of the miR-183/96/182 cluster that are known to play important roles in HC development and function, including Clic5 , Rdx , Ezr , Rac1 , Myo1c , Pvrl 3 and Sox2 , are upregulated in the cochlea. These results suggest that the miR-183/96/182 cluster is essential for stereociliary bundle formation, morphogenesis and function of the cochlear HCs.

Cyclin-dependent kinase 5 (CDK5) is abundantly expressed in post-mitotic cells including neurons. It is involved in multiple cellular events, such as cytoskeletal dynamics, signaling cascades, gene expression, and cell survival, et al. Dysfunction of CDK5 has been associated with a number of neurological disorders. Here we show that CDK5 is expressed in mouse cochlear hair cells, and CDK5 inactivation in hair cells causes hearing loss in mice. CDK5 inactivation has no effect on stereocilia development in the cochlear hair cells. However, it affects stereocilia maintenance, resulting in stereocilia disorganization and eventually stereocilia loss. Consistently, hair cell loss was significantly elevated by CDK5 inactivation. Despite that CDK5 has been shown to play important roles in synapse development and/or function, CDK5 inactivation does not affect the formation of ribbon synapses of cochlear hair cells. Further investigation showed that CDK5 inactivation causes reduced phosphorylation of ERM (ezrin, radixin, and moesin) proteins, which might contribute to the stereocilia deficits. Taken together, our data suggest that CDK5 plays pivotal roles in auditory hair cells, and CDK5 inactivation causes hearing loss in mice.

Mutations in the GJB2 gene (which encodes Connexin26 (Cx26)) account for about a quarter of all cases of non-syndromic deafness. Previous studies have indicated that knockout (KO) of Gjb2 gene during early postnatal days can cause outer hair cell (OHC) loss in mouse models. However, the postnatal spatial distribution pattern of Cx26 in different types of supporting cells (SCs) and the role of such distributions for the survival of OHCs is still obscure. In this study, the spatial distribution patterns of Cx26 in SCs were observed, and based on these observations different spatial Cx26-null mouse models were established in order to determine the effect of changes in the spatial distribution of Cx26 in SCs on the survival of OHCs. At postnatal day (P)3, unlike the synchronous expression of Cx26 along both longitudinal and radial boundaries of most types of SCs, Cx26 expression was primarily observed along the longitudinal boundaries of rows of Deiter’s cells (DCs). From P5 to P7, radial expression of Cx26 was gradually observed between adjacent rows of DCs. When Gjb2 gene was knocked out at random in different types of SCs, about 40% of the total DCs lost Cx26 expression and these Cx26-null DCs were distributed randomly in all three rows of DCs. The mice in this randomly Cx26-null group showed normal hearing and no significant OHC loss. When using a longitudinal KO pattern to induce knockout of Gjb2 gene specifically in the third row of DCs, about 33% of the total DCs lost Cx26 expression in this specific longitudinally Cx26-null group. The mice in this group showed late-onset hearing loss and significant OHC loss, however, the morphology of corresponding DCs was slightly altered. In both experimental groups, no substantial DC loss was observed. These results indicate that longitudinal Cx26-based channels are predominant in DCs during P3–P5. The Cx26 expression along rows of DCs might play a key role in the survival of OHCs, but this longitudinal KO pattern in DCs has a limited effect on DC survival or on its postnatal development.

Tinnitus and hyperacusis are life-disrupting perceptual abnormalities that are often preceded by acoustic overexposure. Animal models of overexposure have suggested a link between these phenomena and neural hyperactivity, i.e., elevated spontaneous rates (SRs) and sound-evoked responses. Prior work has focused on changes in central auditory responses, with less attention paid to the exact nature of the associated cochlear damage. The demonstration that acoustic overexposure can cause cochlear neuropathy without permanent threshold elevation suggests cochlear neuropathy per se may be a key elicitor of neural hyperactivity. We addressed this hypothesis by recording responses in the mouse inferior colliculus (IC) following a bilateral, neuropathic noise exposure. One to three weeks post-exposure, mean SRs were unchanged in mice recorded while awake, or under anesthesia. SRs were also unaffected by more intense, or unilateral exposures. These results suggest that neither neuropathy nor hair cell loss are sufficient to raise SRs in the IC, at least in 7-week-old mice, 1-3 weeks post exposure. However, it is not clear whether our mice had tinnitus. Tone-evoked rate-level functions at the CF were steeper following exposure, specifically in the region of maximal neuropathy. Furthermore, suppression driven by off-CF tones and by ipsilateral noise were reduced. Both changes were especially pronounced in neurons of awake mice. This neural hypersensitivity may manifest as behavioral hypersensitivity to sound - prior work reports that this same exposure causes elevated acoustic startle. Together, these results indicate that neuropathy may initiate a compensatory response in the central auditory system leading to the genesis of hyperacusis.

This data article provides raw auditory evoked brainstem responses (ABRs) from controls and Cav2.3 transgenics, i.e. heterozygous Cav2.3+/- and Cav2.3-/- null mutants. Gender specific ABR recordings were performed in age-matched animals under ketamine/xylazine narcosis. Data presented here include ABRs upon both click and tone burst presentation in the increasing SPL mode using a commercially available ABR setup from Tucker Davis Technologies Inc. (TDT, USA). Detailed information is provided for the sound attenuating cubicle, electrical shielding, electrode parameters, stimulus characteristics and architecture, sampling rate, filtering processes and ABR protocol application during the course of data acquisition and recording. The later are important for subsequent analysis of click and tone burst related hearing thresholds, amplitude growth function and peak latencies. Raw data are available at MENDELEY DATA, DIO: 〈DOI:10.17632/g6ygz2spzx.1〉, URL: 〈https://data.mendeley.com/datasets/g6ygz2spzx/1〉).

Single-sided deafness (SSD) induces cortical neural plastic changes according to duration of deafness. However, it is still unclear how the auditory cortical changes accompany the subcortical neural changes. The present study aimed to find the neural plastic changes in the cortical and subcortical auditory system following adult-onset single-sided deafness (SSD) using Mn-enhanced magnetic resonance imaging (MEMRI). B57BL/6 mice (postnatal 8-week-old) were divided into three groups: the SSD-4-week group (postnatal 12-week-old, n = 11), the SSD-8-week group (postnatal 16-week-old, n = 11), and a normal-hearing control group (postnatal 8-week-old, n = 9). The left cochlea was ablated in the SSD groups. White Gaussian noise was delivered for 24 h before MEMRI acquisition. T 1 -weighted MRI data were analyzed from the cochlear nucleus (CN), superior olivary complex (SOC), lateral lemniscus (LL), inferior colliculus (IC), medial geniculate body (MG), and auditory cortex (AC). The differences in relative Mn 2+ -enhanced signal intensities (Mn 2+ SI) and laterality were analyzed between the groups. Four weeks after the SSD procedure, the ipsilateral side of the SSD showed significantly lower Mn 2+ SI in the CN than the control group. On the other hand, the contralateral side of the SSD demonstrated significantly lower Mn 2+ SI in the SOC, LL, and IC. These decreased Mn 2+ SI values were partially recovered at 8 weeks after the SSD procedure. The interaural Mn 2+ SI differences representing the interaural dominance were highest in CN and then became less prominently higher in the auditory neural system. The SSD-8-week group still showed interaural differences in the CN, LL, and IC. In contrast, the MG and AC did not show any significant intergroup or interaural differences in Mn 2+ SI. In conclusion, subcortical auditory neural activities were decreased after SSD, and the interaural differences were diluted in the higher auditory nervous system. These findings were attenuated with time. Subcortical auditory neural changes after SSD may contribute to the change in tinnitus severity and the outcomes of cochlear implantation in SSD patients.

Many aspects of stress-induced physiological and psychological effects have been characterized in people and animals. However, stress effects on the auditory system are less explored and their mechanisms are not well-understood, in spite of its relevance for a variety of diseases, including tinnitus. To expedite further research of stress-induced changes in the auditory system, here we compare the reactions to stress among Wistar and Lewis rats. The animals were stressed for 24 h, and subsequently we tested the functionality of the outer hair cells (OHCs) using distortion product otoacoustic emissions (DPOAEs) and auditory neurons using evoked auditory brainstem responses (ABR). Lastly, using Western blot, we analyzed the levels of plasticity-related proteins in the inferior colliculus, confirming that the inferior colliculus is involved in the adaptive changes that occur in the auditory system upon stress exposure. Surprisingly, the two strains reacted to stress quite differently: Lewis rats displayed a lowering of their auditory threshold, whereas it was increased in Wistar rats. These functional differences were seen in OHCs of the apical region (low frequencies) and in the auditory neurons (across several frequencies) from day 1 until 2 weeks after the experimental stress ended. Wistar and Lewis rats may thus provide models for auditory threshold increase and decrease, respectively, which can both be observed in different patients in response to stress.

Age-related hearing loss (AHL) is the most common sensory disorder in the elderly population, and the etiologies are diverse. To understand the underlying mechanisms of AHL, one strategy is to identify correlates of the disease for comprehensive evaluation of treatment approaches. Dysfunction and degeneration of spiral ganglion neurons (SGNs) are major contributors to AHL. Previously, we showed that one of the changes in the aging auditory system is SGN excitability increase in mice. Since hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles in determining neuronal excitability, we predicted that HCN channels in SGNs are involved in AHL. To investigate the contribution of HCN channels to AHL, we examined the expression and biophysical properties of HCN channels in SGNs from adult (2-3 months) and 11-12-month-old mice. We report a dramatic increase of HCN channel current (Ih) in SGNs in old mice (11-12 months old). The results matched well with increased expression of HCN1 and HCN2 subunits, suggesting that upregulation of HCN channels in SGNs is one of the important facets of the aging SGNs. Moreover, the activity of Ih produced a major impact on the firing properties of SGNs in older mice. The upregulation of Ih may contribute to AHL by regulating SGN excitability. We assessed whether increased SGNs excitability dovetail with neurodegeneration. Apoptosis-inducing factor (AIF)-mediated apoptosis in SGNs was observed in old mice and activation of HCN channels mediates AIF activation. Thus, these findings demonstrate stark correlation between age-dependent increased expression of HCN channels and Ih, and apoptosis in SGNs, which may contribute towards the varied mechanisms of AHL.

Vitamin A deficiency (VAD) produces various pathologic phenotypes in humans and animals. However, evidence regarding the effect of VAD on hearing function has been inconsistent. In this study, we evaluated the effect of VAD on hearing function in two mouse models of VAD. Hearing ability was evaluated on the basis of auditory brainstem response from 3 to 20 weeks after birth in C57BL/6 (pigmented) and imprinting control region (albino) mice. The two mice strains were divided into the VAD (purified vitamin A-free diet from 7 days after pregnancy) and control (normal diet) groups. Albino VAD mice exhibited hearing loss after 6 weeks and became deaf at 18 weeks. Histological findings revealed degenerative changes in outer hair cells and neuronal loss in the spiral ganglion in albino VAD mice. In contrast, pigmented VAD mice, except those with middle-ear infection, showed no significant hearing loss. Interestingly, pigmented VAD mice exhibited melanocyte activation in the stria vascularis and upregulation of tyrosinase. Recovery of hearing after noise exposure was poorer in pigmented VAD mice than in control mice. In conclusion, complete VAD might be related to age-related or noise-induced hearing loss in mice, protection against which might involve melanocyte activation.

Tinnitus alters auditory-somatosensory plasticity in the cochlear nucleus (CN). Correspondingly, bimodal auditory-somatosensory stimulation treatment attenuates tinnitus, both in animals and humans (Marks et al., 2018). Therefore, we hypothesized that tinnitus is associated with altered somatosensory innervation of the CN. Here, we studied the expression of vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) in the CN, which reveals glutamatergic projections from the cochlea as well as somatosensory systems to this brainstem auditory center. Guinea pigs were unilaterally exposed to narrowband noise and behaviorally tested for tinnitus using gap-prepulse inhibition of the acoustic startle. Following physiological and behavioral measures, brain sections were immunohistochemically stained for VGLUT1 or VGLUT2. Puncta density was determined for each region of the ipsilateral and contralateral CN. Tinnitus was associated with an ipsilateral upregulation of VGLUT2 puncta density in the granule cell domain (GCD) and anteroventral CN (AVCN). Furthermore, there was a tinnitus-associated interaural asymmetry for VGLUT1 expression in the AVCN and deep layer of the dorsal CN (DCN3), due to contralateral downregulation of VGLUT1 expression. These tinnitus-related glutamatergic imbalances were reversed upon bimodal stimulation treatment. Tinnitus-associated ipsilateral upregulation of VGLUT2-positive projections likely derives from somatosensory projections to the GCD and AVCN. This upregulation may underlie the neurophysiological hallmarks of tinnitus in the CN. Reversing the increased ipsilateral glutamatergic innervation in the CN is likely a key mechanism in treating tinnitus.

The sensory cells that are responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with the OHCs being necessary for sound sensitivity and tuning1. Both cell types are thought to arise from common progenitors; however, our understanding of the factors that control the fate of IHCs and OHCs remains limited. Here we identify Ikzf2 (which encodes Helios) as an essential transcription factor in mice that is required for OHC functional maturation and hearing. Helios is expressed in postnatal mouse OHCs, and in the cello mouse model a point mutation in Ikzf2 causes early-onset sensorineural hearing loss. Ikzf2cello/cello OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of crucial OHC-expressed genes such as Slc26a5 (which encodes prestin) and Ocm. Moreover, we show that ectopic expression of Ikzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating that Ikzf2 can partially shift the IHC transcriptome towards an OHC-like identity.

Remarkably, the central auditory system can modify the strength of its sound-evoked neural response based on prior acoustic experiences, a phenomenon referred to as central gain. Gain changes are well documented following traumatic noise exposure, but much less is known about central gain dynamics following prolonged exposure to low-level noise, a common acoustic experience in many urban and work environments. We recently reported that the neural output of the cochlea is reduced, while gain was enhanced in the inferior colliculus (IC) following a 5-week exposure to 75 dB noise. To determine if similar effects were present at even lower intensities, we exposed rats to a 65 dB noise expecting to see little to no change in the cochlea or IC. The exposure had little effect on distortion product otoacoustic emissions and did not cause any hair cell loss. However, the amplitude of the CAP, which reflects the neural output of cochlea, was depressed by 50-75%. Surprisingly, neural responses from the IC were enhanced up to 70%, mainly at frequencies within the noise exposure band. One-week post-exposure, CAP amplitudes returned to normal at frequencies within or above the exposure band, whereas responses evoked by frequencies below the exposure band were enhanced by more than 80%. In contrast, IC responses below the exposure frequency were depressed 10-20% whereas responses within the exposure frequency band were enhanced 10-20%. Thus, the central auditory system dynamically up- and down-regulates its gain to maintain supra-threshold neural responses within a narrow homeostatic range; a function that likely contributes to the prevention of sounds from being perceived as muffled or too loud.

The ability to accurately integrate or bind stimuli from more than one sensory modality is highly dependent on the features of the stimuli, such as their intensity and relative timing. Previous studies have demonstrated that the ability to perceptually bind stimuli is impaired in various clinical conditions such as autism, dyslexia, schizophrenia, as well as aging. However, it remains unknown if adult-onset hearing loss, separate from aging, influences audiovisual temporal acuity. In the present study, rats were trained using appetitive operant conditioning to perform an audiovisual temporal order judgment (TOJ) task or synchrony judgment (SJ) task in order to investigate the nature and extent that audiovisual temporal acuity is affected by adult-onset hearing loss, with a specific focus on the time-course of perceptual changes following loud noise exposure. In our first series of experiments, we found that audiovisual temporal acuity in normal-hearing rats was influenced by sound intensity, such that when a quieter sound was presented, the rats were biased to perceive the audiovisual stimuli as asynchronous (SJ task), or as though the visual stimulus was presented first (TOJ task). Psychophysical testing demonstrated that noise-induced hearing loss did not alter the rats' temporal sensitivity 2-3 weeks post-noise exposure, despite rats showing an initial difficulty in differentiating the temporal order of audiovisual stimuli. Furthermore, consistent with normal-hearing rats, the timing at which the stimuli were perceived as simultaneous (i.e., the point of subjective simultaneity, PSS) remained sensitive to sound intensity following hearing loss. Contrary to the TOJ task, hearing loss resulted in persistent impairments in asynchrony detection during the SJ task, such that a greater proportion of trials were now perceived as synchronous. Moreover, psychophysical testing found that noise-exposed rats had altered audiovisual synchrony perception, consistent with impaired audiovisual perceptual binding (e.g., an increase in the temporal window of integration on the right side of simultaneity; right temporal binding window (TBW)). Ultimately, our collective results show for the first time that adult-onset hearing loss leads to behavioral plasticity of audiovisual perception, characterized by a rapid recalibration of temporal sensitivity but a persistent impairment in the perceptual binding of audiovisual stimuli.

Electrical nerve recording and stimulation technologies are critically needed to monitor and modulate nerve activity to treat a variety of neurological diseases. However, current neuromodulation technologies presented in the literature or commercially available products cannot support simultaneous recording and stimulation on the same nerve. To solve this problem, a new bidirectional neuromodulation system-on-chip (SoC) is proposed in this paper, which includes a frequency-shaping neural recorder and a fully integrated neural stimulator with charge balancing capability. In addition, auxiliary circuits consisting of power management and data transmission circuits are designed to provide the necessary power supply for the SoC and the bidirectional data communication between the SoC and an external computer via a universal serial bus (USB) interface, respectively. To achieve sufficient low input noise for sensing nerve activity at a sub-10 μ V range, several noise reduction techniques are developed in the neural recorder. The designed SoC was fabricated in a 0.18 μ m high-voltage Bipolar CMOS DMOS (BCD) process technology that was described in a previous publication and it has been recently tested in animal experiments that demonstrate the proposed SoC is capable of achieving reliable and simultaneous electrical stimulation and recording on the same nerve.