Auditory Research publications

Noise exposure or ototoxic drugs instigate various types of damage to the cochlea, resulting in hearing loss (HL). While the incidence of HL is growing continuously, there are, so far, no adequate drugs to prevent or treat HL. Avenanthramide (AVN), a natural product extracted from oats, has been reported to possess anti-oxidant/inflammatory properties, and protect several types of cells. In this study, we investigated whether AVN-C can protect auditory hair cells, and preserve hearing from noise trauma and ototoxic drugs. Wild-type C57BL/6 mice were used to generate several HL models. Serum and perilymphatic fluid samples were analyzed using mass spectrophotometry to detect AVN-C. AVN-C crossed the blood-labyrinth barrier, and was detected in the perilymph after systemic injection. Pretreatment by AVN-C 24 h before exposure to temporary threshold shift noise contributed to the preserving hearing. Moreover, in the case of permanent threshold shift, AVN-C provided significant protection from noise. AVN-C also strongly protected against deterioration in hearing due to kanamycin and furosemide (K + F). According to the results of our scanning electron microscopy analysis, many outer hair cells (OHCs) were destroyed by noise trauma, while AVN-C prevented these losses. OHC loss due to K + F was even more severe, even affecting the apex. Strikingly, AVN-C treatment maintained OHCs at a level comparable to normal cochlea. AVN-C reduced the dichlorofluorescin (DCF)-positive population in gentamicin-treated HEI-OC1 in vitro. The expressions of TNF-a, BAK, IL-1b, and Bcl-2 were attenuated by AVN-C, revealing its antioxidant effects. The results of this study show that AVN-C crosses the blood-labyrinth barrier and provide a significant protection against noise- and drug-induced ototoxicity. Hence, AVN-C is a good candidate for future therapy aimed at protecting against sensorineural HL.

Previous studies have reported that rearing infant rat pups in continuous moderate-level noise delayed the formation of topographic representational order and the refinement of response selectivity in the primary auditory (A1) cortex. The present study further verified that exposure to long-term moderate-intensity white noise (70 dB sound pressure level) from postnatal day (P) 12 to P30 elevated the hearing thresholds of infant rats. Compared with age-matched control rats, noise exposure (NE) rats had elevated hearing thresholds ranging from low to high frequencies, accompanied by decreased amplitudes and increased latencies of the two initial auditory brainstem response waves. The power of raw local field potential oscillations and high-frequency β oscillation in the A1 cortex of NE rats were larger, whereas the power of high-frequency γ oscillation was smaller than that of control rats. In addition, the expression levels of five glutamate receptor (GluR) subunits in the A1 cortex of NE rats were decreased with laminar specificity. These results suggest that the altered neural excitability and decreased GluR expression may underlie the delay of functional maturation in the A1 cortex, and may have implications for the treatment of hearing impairment induced by environmental noise.

In the rodent auditory system, the primary cortex is subdivided into two regions, both receiving direct inputs from the auditory thalamus: the primary auditory cortex (A1) and the anterior auditory field (AAF). Although neurons in the two regions display different response properties, like response latency, firing threshold or tuning bandwidth, it is still not clear whether they process sound in a distinct way. Using in vivo electrophysiological recordings in the mouse auditory cortex, we found that AAF neurons have significantly stronger responses to tone offset than A1 neurons. AAF neurons also display faster and more transient responses than A1 neurons. Additionally, offset responses in AAF – unlike in A1, increase with sound duration. Local field potential (LFP) and laminar analyses suggest that the differences in sound responses between these two primary cortices are both of subcortical and intracortical origin. These results emphasize the potentially critical role of AAF for temporal processing. Our study reveals a distinct role of two primary auditory cortices in tone processing and highlights the complexity of sound encoding at the cortical level.

Frontal areas of the mammalian cortex are thought to be important for cognitive control and complex behaviour. These areas have been studied mostly in humans, non-human primates and rodents. In this article, we present a quantitative characterization of response properties of a frontal auditory area responsive to sound in the bat brain, the frontal auditory field (FAF). Bats are highly vocal animals and they constitute an important experimental model for studying the auditory system. At present, little is known about neuronal sound processing in the bat FAF. We combined electrophysiology experiments and computational simulations to compare the response properties of auditory neurons found in the bat FAF and auditory cortex (AC) to simple sounds (pure tones). Anatomical studies have shown that the latter provide feedforward inputs to the former. Our results show that bat FAF neurons are responsive to sounds, however, when compared to AC neurons, they presented sparser, less precise spiking and longer-lasting responses. Based on the results of an integrate-and-fire neuronal model, we speculate that slow, low-threshold, synaptic dynamics could contribute to the changes in activity pattern that occur as information travels through cortico-cortical projections from the AC to the FAF.

Sensory hair cells are mechanoreceptors required for hearing and balance functions. From embryonic development, hair cells acquire apical stereociliary bundles for mechanosensation, basolateral ion channels that shape receptor potential, and synaptic contacts for conveying information centrally. These key maturation steps are sequential and presumed coupled; however, whether hair cells emerging postnatally mature similarly is unknown. Here, we show that in vivo postnatally generated and regenerated hair cells in the utricle, a vestibular organ detecting linear acceleration, acquired some mature somatic features but hair bundles appeared nonfunctional and short. The utricle consists of two hair cell subtypes with distinct morphological, electrophysiological and synaptic features. In both the undamaged and damaged utricle, fate-mapping and electrophysiology experiments showed that Plp1+ supporting cells took on type II hair cell properties based on molecular markers, basolateral conductances and synaptic properties yet stereociliary bundles were absent, or small and nonfunctional. By contrast, Lgr5+ supporting cells regenerated hair cells with type I and II properties, representing a distinct hair cell precursor subtype. Lastly, direct physiological measurements showed that utricular function abolished by damage was partially regained during regeneration. Together, our data reveal a previously unrecognized aberrant maturation program for hair cells generated and regenerated postnatally and may have broad implications for inner ear regenerative therapies.

The mismatch negativity (MMN) is an ERP component seen in response to unexpected “novel” stimuli, such as in an auditory oddball task. The MMN is of wide interest and application, but the neural responses that generate it are poorly understood. This is in part due to differences in design and focus between animal and human oddball paradigms. For example, one of the main explanatory models, the “predictive error hypothesis”, posits differences in timing and selectivity between signals carried in auditory and prefrontal cortex (PFC). However, these predictions have not been fully tested because (1) noninvasive techniques used in humans lack the combined spatial and temporal precision necessary for these comparisons and (2) single-neuron studies in animal models, which combine necessary spatial and temporal precision, have not focused on higher order contributions to novelty signals. In addition, accounts of the MMN traditionally do not address contributions from subcortical areas known to be involved in novelty detection, such as the amygdala. To better constrain hypotheses and to address methodological gaps between human and animal studies, we recorded single neuron activity from the auditory cortex, dorsolateral PFC, and basolateral amygdala of two macaque monkeys during an auditory oddball paradigm modeled after that used in humans. Consistent with predictions of the predictive error hypothesis, novelty signals in PFC were generally later than in auditory cortex and were abstracted from stimulus-specific effects seen in auditory cortex. However, we found signals in amygdala that were comparable in magnitude and timing to those in PFC, and both prefrontal and amygdala signals were generally much weaker than those in auditory cortex. These observations place useful quantitative constraints on putative generators of the auditory oddball-based MMN and additionally indicate that there are subcortical areas, such as the amygdala, that may be involved in novelty detection in an auditory oddball paradigm.

Background: Recent studies in a variety of animal models including rodents, monkeys, and humans suggest that transcranial focused ultrasound (tFUS) has considerable promise for non-invasively modulating neural activity with the ability to target deep brain structures. However, concerns have been raised that motor responses evoked by tFUS may be due to indirect activation of the auditory pathway rather than direct activation of motor circuits. Objective: In this study, we sought to examine the involvement of peripheral auditory system activation from tFUS stimulation applied to elicit motor responses. The purpose was to determine to what extent ultrasound induced auditory artifact could be a factor in ultrasound motor neuromodulation. Methods: In this study, tFUS-induced electromyography (EMG) signals were recorded and analyzed in wild-type (WT) normal hearing mice and two strains of genetically deaf mice to examine the involvement of the peripheral auditory system in tFUS-stimulated motor responses. In addition, auditory brainstem responses (ABRs) were measured to elucidate the effect of the tFUS stimulus envelope on auditory and motor responses. We also varied the tFUS stimulation duration to measure its effect on motor response duration. Results: We show, first, that the sharp edges in a tFUS rectangular envelope stimulus activate the peripheral afferent auditory pathway and, second, that smoothing these edges eliminates the auditory responses without affecting the motor responses in normal hearing WT mice. We further show that by eliminating peripheral auditory activity using two different strains of deaf knockout mice, motor responses are the same as in normal hearing WT mice. Finally, we demonstrate a high correlation between tFUS pulse duration and EMG response duration. Conclusion: These results support the concept that tFUS-evoked motor responses are not a result of stimulation of the peripheral auditory system.

Distortion product otoacoustic emissions (DPOAEs) evoked by two pure tones carry information about the mechanisms that generate and shape them. Thus, DPOAEs hold promise for providing powerful noninvasive diagnostic details of cochlear operations, middle ear (ME) transmission, and impairments. DPOAEs are sensitive to ME function because they are influenced by ME transmission twice, i.e., by the inward-going primary tones in the forward direction and the outward traveling DPOAEs in the reverse direction. However, the effects of ME injuries on DPOAEs have not been systematically characterized. The current study focused on exploring the utility of DPOAEs for examining ME function by methodically characterizing DPOAEs and ME transmission under pathological ME conditions, specifically under conditions of tympanic-membrane (TM) perforation and spontaneous healing. Results indicated that DPOAEs were measurable with TM perforations up to ∼50%, and DPOAE reductions increased with increasing size of the TM perforation. DPOAE reductions were approximately flat across test frequencies when the TM was perforated about 10% (<1/8 of pars tensa) or less. However, with perforations greater than 10%, DPOAEs decreased further with a low-pass filter shape, with ∼30 dB loss at frequencies below 10 kHz and a quick downward sloping pattern at higher frequencies. The reduction pattern of DPOAEs across frequencies was similar to but much greater than, the directly measured ME pressure gain in the forward direction, which suggested that reduction in the DPOAE was a summation of losses of ME ear transmission in both the forward and reverse directions. Following 50% TM perforations, DPOAEs recovered over a 4-week spontaneously healing interval, and these recoveries were confirmed by improvements in auditory brainstem response (ABR) thresholds. However, up to 4-week post-perforation, DPOAEs never fully recovered to the levels obtained with normal intact TM, consistent with the incomplete recovery of ABR thresholds and ME transmission, especially at high-frequency regions, which could be explained by an irregularly dense and thickened healed TM. Since TM perforations in patients are commonly caused by either trauma or infection, the present results contribute towards providing insight into understanding ME transmission under pathological conditions as well as promoting the application of DPOAEs in the evaluation and diagnosis of deficits in the ME-transmission system.

Background: As an alternative pathway to air conduction, bone conduction is a multipathway process that transmits sound energy to the inner ear through the skull in general. Based on this mechanism, bone conduction devices (BCDs) have been used widely in the rehabilitation of hearing loss. Although great efforts have been devoted to improving BCDs, drawbacks still exist in most categories of BCDs due to the complicated process of bone conduction. We hypothesized that if a bone conduction transducer was placed on the cochlea to stimulate it directly, the attenuation would be minimized, and the frequency dependency would be different from that of the vibratory response induced by traditional BCDs. This study aimed to explore the feasibility of direct promontory stimulation and to investigate its frequency-response characteristics. Methods: Measurements were conducted in twelve cat ears. To stimulate the promontory directly, the floating mass transducer (FMT) of the Vibrant Soundbridge© (VSB) implant was glued to the promontory coupled with an oval window (OW) coupler. Auditory brainstem response (ABR) and laser Doppler vibrometry (LDV) measurements were used to evaluate the auditory response induced by the FMT. In both measurements, the FMT was driven by direct voltage stimuli. Results: ABR waves could be induced under direct promontory stimulation by the FMT. In the frequency range of 1-12 kHz, the variation in the voltage threshold level were limited to 16 dB SPL with a maximum of 0.2 V at 1 kHz and a minimum of 0.04 V at 10 kHz. In the LDV measurements and the relative motion of the round window membrane (RWM) and the promontory were used to evaluate the cochlear response. The LDV results indicated a weak frequency dependency from 1 to 12 kHz. Conclusion: Different from traditional stimulation via transcranial bone conduction, direct promontory stimulation is a new method in which a small bone conduction transducer stimulates the cochlear shell directly. The current experimental data demonstrate that it is feasible to generate sensations through bone conduction by stimulating the cochlea directly. Furthermore, the cochlear response induced by this type of stimulus in cats was weakly frequency dependent at frequencies ranging from 1 to 12 kHz. This study may provide a basis for the design of new transducers that can perform well over a wide range of frequencies.

When two voices compete, listeners can segregate and identify concurrent speech sounds using pitch (fundamental frequency, F0) and timbre (harmonic) cues. Speech perception is also hindered by the signal-to-noise ratio (SNR). How clear and degraded concurrent speech sounds are represented at early, pre-attentive stages of the auditory system is not well understood. To this end, we measured scalp-recorded frequency-following responses (FFR) from the EEG while human listeners heard two concurrently presented, steady-state (time-invariant) vowels whose F0 differed by zero or four semitones (ST) presented diotically in either clean (no noise) or noise-degraded (+5dB SNR) conditions. Listeners also performed a speeded double vowel identification task in which they were required to identify both vowels correctly. Behavioral results showed that speech identification accuracy increased with F0 differences between vowels, and this perceptual F0 benefit was larger for clean compared to noise degraded (+5dB SNR) stimuli. Neurophysiological data demonstrated more robust FFR F0 amplitudes for single compared to double vowels and considerably weaker responses in noise. F0 amplitudes showed speech-on-speech masking effects, along with a non-linear constructive interference at 0ST, and suppression effects at 4ST. Correlations showed that FFR F0 amplitudes failed to predict listeners' identification accuracy. In contrast, FFR F1 amplitudes were associated with faster reaction times, although this correlation was limited to noise conditions. The limited number of brain-behavior associations suggests subcortical activity mainly reflects exogenous processing rather than perceptual correlates of concurrent speech perception. Collectively, our results demonstrate that FFRs reflect pre-attentive coding of concurrent auditory stimuli that only weakly predict the success of identifying concurrent speech.

Since most dominant human mutations are single nucleotide substitutions1,2, we explored gene editing strategies to disrupt dominant mutations efficiently and selectively without affecting wild-type alleles. However, single nucleotide discrimination can be difficult to achieve3 because commonly used endonucleases, such as Streptococcus pyogenes Cas9 (SpCas9), can tolerate up to seven mismatches between guide RNA (gRNA) and target DNA. Furthermore, the protospacer-adjacent motif (PAM) in some Cas9 enzymes can tolerate mismatches with the target DNA3,4. To circumvent these limitations, we screened 14 Cas9/gRNA combinations for specific and efficient disruption of a nucleotide substitution that causes the dominant progressive hearing loss, DFNA36. As a model for DFNA36, we used Beethoven mice5, which harbor a point mutation in Tmc1, a gene required for hearing that encodes a pore-forming subunit of mechanosensory transduction channels in inner-ear hair cells6. We identified a PAM variant of Staphylococcus aureus Cas9 (SaCas9-KKH) that selectively and efficiently disrupted the mutant allele, but not the wild-type Tmc1/TMC1 allele, in Beethoven mice and in a DFNA36 human cell line. Adeno-associated virus (AAV)-mediated SaCas9-KKH delivery prevented deafness in Beethoven mice up to one year post injection. Analysis of current ClinVar entries revealed that ~21% of dominant human mutations could be targeted using a similar approach.

Hypothesis: Use of micro-mechanical control during cochlear implant (CI) electrode insertion will result in reduced number and magnitude of pressure transients when compared with standard insertion by hand. Introduction: With increasing focus on hearing preservation during CI surgery, atraumatic electrode insertion is of the utmost importance. It has been established that large intracochlear pressure spikes can be generated during the insertion of implant electrodes. Here, we examine the effect of using a micro-mechanical insertion control tool on pressure trauma exposures during implantation. Methods: Human cadaveric heads were surgically prepared with an extended facial recess. Electrodes from three manufacturers were placed both by using a micro-mechanical control tool and by hand. Insertions were performed at three different rates: 0.2 mm/s, 1.2 mm/s, and 2 mm/s (n = 20 each). Fiber-optic sensors measured pressures in scala vestibuli and tympani. Results: Electrode insertion produced pressure transients up to 174 dB SPL. ANOVA revealed that pressures were significantly lower when using the micro-mechanical control device compared with insertion by hand ( p << 0.001). No difference was noted across electrode type or speed. Chi-square analysis showed a significantly lower proportion of insertions contained pressure spikes when the control system was used ( p << 0.001). Conclusion: Results confirm previous data that suggest CI electrode insertion can cause pressure transients with intensities similar to those elicited by high-level sounds. Results suggest that the use of a micro-mechanical insertion control system may mitigate trauma from pressure events, both by reducing the amplitude and the number of pressure spikes resulting from CI electrode insertion.

Many forms of behavior require selective amplification of neuronal representations of relevant environmental signals. Emotional learning enhances sensory responses in the sensory cortex, yet the underlying circuits remain poorly understood. We identify a pathway between the basolateral amygdala (BLA), an emotional learning center in the mouse brain, and the inhibitory reticular nucleus of the thalamus (TRN). Optogenetic activation of BLA suppressed spontaneous, but not tone-evoked, activity in the auditory cortex (AC), amplifying tone-evoked responses. Viral tracing identified BLA projections terminating at TRN. Optogenetic activation of amygdala-TRN projections further amplified tone-evoked responses in the auditory thalamus and cortex. The results are explained by a computational model of the thalamocortical circuitry, in which activation of TRN by BLA primes thalamocortical neurons to relay relevant sensory input. This circuit mechanism shines a neural spotlight on behaviorally relevant signals and provides a potential target for the treatment of neuropsychological disorders.

Background: Middle ear (intratympanic, IT) administration is a promising therapeutic method as it offers the possibility of achieving high inner ear drug concentrations with low systemic levels, thus minimizing the risk of systemic side effects and drug-drug interactions. Premature elimination through the Eustachian tube may be reduced by stabilizing drug solutions with a hydrogel, but this raises the secondary issue of conductive hearing loss. Aim: This study aimed to investigate the properties of a chitosan-based particulate hydrogel formulation when used as a drug carrier for IT administration in an in vivo model of ototoxicity. Materials and methods: Two particulate chitosan-based IT delivery systems, Thio-25 and Thio-40, were investigated in albino guinea pigs (n = 94). Both contained the hearing protecting drug candidate sodium thiosulfate with different concentrations of chitosan gel particles (25% vs. 40%). The safety of the two systems was explored in vivo. The most promising system was then tested in guinea pigs subjected to a single intravenous injection with the anticancer drug cisplatin (8 mg/kg b.w.), which has ototoxic side effects. Hearing status was evaluated with acoustically evoked frequency-specific auditory brainstem response (ABR) and hair cell counting. Finally, in vivo magnetic resonance imaging was used to study the distribution and elimination of the chitosan-based system from the middle ear cavity in comparison to a hyaluronan-based system. Results: Both chitosan-based IT delivery systems caused ABR threshold elevations (p < 0.05) that remained after 10 days (p < 0.05) without evidence of hair cell loss, although the elevation induced by Thio-25 was significantly lower than for Thio-40 (p < 0.05). Thio-25 significantly reduced cisplatin-induced ABR threshold elevations (p < 0.05) and outer hair cell loss (p < 0.05). IT injection of the chitosan- and hyaluronan-based systems filled up most of the middle ear space. There were no significant differences between the systems in terms of distribution and elimination. Conclusion: Particulate chitosan is a promising drug carrier for IT administration. Future studies should assess whether the physical properties of this technique allow for a smaller injection volume that would reduce conductive hearing loss.

The left hemisphere’s dominance in processing social communication has been known for over a century, but the mechanisms underlying this lateralized cortical function are poorly understood. Here, we compare the structure, function, and development of each auditory cortex (ACx) in the mouse to look for specializations that may underlie lateralization. Using Fos brain volume imaging, we found greater activation in the left ACx in response to vocalizations, while the right ACx responded more to frequency sweeps. In vivo recordings identified hemispheric differences in spectrotemporal selectivity, reinforcing their functional differences. We then compared the synaptic connectivity within each hemisphere and discovered lateralized circuit-motifs that are hearing experience-dependent. Our results suggest a specialist role for the left ACx, focused on facilitating the detection of specific vocalization features, while the right ACx is a generalist with the ability to integrate spectrotemporal features more broadly.

Gentamicin, one of the most widely used aminoglycoside antibiotics, is known to have toxic effects on the inner ear. Taken up by cochlear hair cells and spiral ganglion neurons (SGNs), gentamicin induces the accumulation of reactive oxygen species (ROS) and initiates apoptosis or programmed cell death, resulting in a permanent and irreversible hearing loss. Since the survival of SGNs is specially required for cochlear implant, new procedures that prevent SGN cell loss are crucial to the success of cochlear implantation. ROS modulates the activity of the mammalian target of rapamycin (mTOR) signaling pathway, which mediates apoptosis or autophagy in cells of different organs. However, whether mTOR signaling plays an essential role in the inner ear and whether it is involved in the ototoxic side effects of gentamicin remain unclear. In the present study, we found that gentamicin induced apoptosis and cell loss of SGNs in vivo and significantly decreased the density of SGN and outgrowth of neurites in cultured SGN explants. The phosphorylation levels of ribosomal S6 kinase and elongation factor 4E binding protein 1, two critical kinases in the mTOR complex 1 (mTORC1) signaling pathway, were modulated by gentamicin application in the cochlea. Meanwhile, rapamycin, a specific inhibitor of mTORC1, was co-applied with gentamicin to verify the role of mTOR signaling. We observed that the density of SGN and outgrowth of neurites were significantly increased by rapamycin treatment. Our finding suggests that mTORC1 is hyperactivated in the gentamicin-induced degeneration of SGNs, and rapamycin promoted SGN survival and outgrowth of neurites.

This study describes sound localization and speech-recognition-in-noise abilities of a cochlear-implant user with electro-acoustic stimulation (EAS) in one ear, and a hearing aid in the contralateral ear. This listener had low-frequency, up to 250 Hz, residual hearing within the normal range in both ears. The objective was to determine how hearing devices affect spatial hearing for an individual with substantial unaided low-frequency residual hearing. Sound-localization performance was assessed for three sounds with different bandpass characteristics: low center frequency (100-400 Hz), mid center frequency (500-1,500 Hz) and high frequency broad-band (500-20,000 Hz) noise. Speech recognition was assessed with the Dutch Matrix sentence test presented in noise. Tests were performed while the listener used several on-off combinations of the devices. The listener localized low-center frequency sounds well in all hearing conditions, but mid-center frequency and high frequency broadband sounds were localized well almost exclusively in the completely unaided condition (mid-center frequency sounds were also localized well with the EAS device alone). Speech recognition was best in the fully aided condition with speech presented in the front and noise presented at either side. Furthermore, there was no significant improvement in speech recognition with all devices on, compared to when the listener used her cochlear implant only. Hearing aids and cochlear implant impair high frequency spatial hearing due to improper weighing of interaural time and level difference cues. The results reinforce the notion that hearing symmetry is important for sound localization. The symmetry is perturbed by the hearing devices for higher frequencies. Speech recognition depends mainly on hearing through the cochlear implant and is not significantly improved with the added information from hearing aids. A contralateral hearing aid provides benefit when the noise is spatially separated from the speech. However, this benefit is explained by the head shadow in that ear, rather than by an ability to spatially segregate noise from speech, as sound localization was perturbed with all devices in use.

TRIOBP remodels the cytoskeleton by forming unusually dense F-actin bundles and is implicated in human cancer, schizophrenia, and deafness. Mutations ablating human and mouse TRIOBP-4 and TRIOBP-5 isoforms are associated with profound deafness, as inner ear mechanosensory hair cells degenerate after stereocilia rootlets fail to develop. However, the mechanisms regulating formation of stereocilia rootlets by each TRIOBP isoform remain unknown. Using 3 new Triobp mouse models, we report that TRIOBP-5 is essential for thickening bundles of F-actin in rootlets, establishing their mature dimensions and for stiffening supporting cells of the auditory sensory epithelium. The coiled-coil domains of this isoform are required for reinforcement and maintenance of stereocilia rootlets. A loss of TRIOBP-5 in mouse results in dysmorphic rootlets that are abnormally thin in the cuticular plate but have increased widths and lengths within stereocilia cores, and causes progressive deafness recapitulating the human phenotype. Our study extends the current understanding of TRIOBP isoform–specific functions necessary for life-long hearing, with implications for insight into other TRIOBPopathies.

Purpose Growing evidence supports the inclusion of perceptual tests that quantify the processing of temporal fine structure (TFS) in clinical hearing assessment. Many tasks have been used to evaluate TFS in the laboratory that vary greatly in the stimuli used and whether the judgments require monaural or binaural comparisons of TFS. The purpose of this study was to compare laboratory measures of TFS for inclusion in a battery of suprathreshold auditory tests. A subset of available TFS tasks were selected on the basis of potential clinical utility and were evaluated using metrics that focus on characteristics important for clinical use. Method TFS measures were implemented in replication of studies that demonstrated clinical utility. Monaural, diotic, and dichotic measures were evaluated in 11 young listeners with normal hearing. Measures included frequency modulation (FM) tasks, harmonic frequency shift detection, interaural phase difference (TFS–low frequency), interaural time difference (ITD), monaural gap duration discrimination, and tone detection in noise with and without a difference in interaural phase (N 0 S 0 , N 0 S π ). Data were compared with published results and evaluated with metrics of consistency and efficiency. Results Thresholds obtained were consistent with published data. There was no evidence of predictive relationships among the measures consistent with a homogenous group. The most stable tasks across repeated testing were TFS–low frequency, diotic and dichotic FM, and N 0 S π . Monaural and diotic FM had the lowest normalized variance and were the most efficient accounting for differences in total test duration, followed by ITD. Conclusions Despite a long stimulus duration, FM tasks dominated comparisons of consistency and efficiency. Small differences separated the dichotic tasks FM, ITD, and N 0 S π . Future comparisons following procedural optimization of the tasks will evaluate clinical efficiency in populations with impairment.

Aminoglycoside ototoxicity is common in clinical practice but reliable protective agents currently do not exist. Aminoglycoside regimens causing ototoxicity in different laboratory animals are under investigation. The assessment method used most commonly to determine auditory effects is the auditory brainstem response (ABR). Distortion product otoacoustic emissions (DPOAE) have been used less frequently. A precise recommendation on the specific method to assess peripheral auditory function before and after aminoglycoside toxicity in mice does not exist. In order to evaluate various mouse models for ototoxic injury caused by various aminoglycoside regimens, there is a need for performing preliminary tests in small cohorts before large experiments. The aim of our study was to investigate different aminoglycoside regimens that cause substantial ototoxic damage in vivo. Aminoglycosides are safe and produce a detectable hearing threshold shift in a small cohort of mice that can be used as a model for preliminary tests. Different ototoxic regimens were assessed by ABR and DPOAE measurements pre- and post-treatment. Further, the sensory cell loss was quantified by counting hair cells in the cochlea. It was revealed that an ototoxic regimen with kanamycin twice daily for 15 consecutive days is safe, well tolerated and produces an early significant hearing threshold shift detected by DPOAE in a small cohort of mice. The study compared ABR and DPOAE in mentioned regimens for the first time and illustrated that DPOAE is well suited for detecting hearing threshold shifts in high frequencies before ABR threshold shifts occur in accordance with predominating outer hair cell damage mainly in the basal turn of the cochlea.