Publications using TDT

Validating hearing-aid fittings in prelingual infants is challenging because typical measures (aided audiometry, etc.) are impossible with infants. One objective alternative uses an aided auditory steady-state response (ASSR) measurement. To make an appropriate measurement, the hearing aid’s signal-processing features must be activated (or deactivated) as if the ASSR stimulus was real speech. Rather than manipulating the hearing-aid settings to achieve this, an ASSR stimulus with speech-like properties was developed. This promotes clinical simplicity and face validity of the validation. The stimulus consists of narrow-band CE-Chirps®, modified to mimic the International Speech Test Signal (ISTS). This study examines the cost of introducing the speech-like features into the ASSR stimulus. Thus, 90 to 100 Hz ASSRs were recorded to the ISTS-modified stimulus as well as an equivalent stimulus without the ISTS modification, presented through insert phones to 10 young normal-hearing subjects. Noise-corrected ASSR magnitudes and clinically relevant detection times were estimated and analyzed with mixed-model analyses of variance. As a supplement, the observed changes to the ASSR magnitudes were compared with an objective characterization of the stimuli based on modulation power. The main findings were a reduction in ASSR magnitude of 4 dB and an increase in detection time by a factor of 1.5 for the ISTS-modified stimulus compared with the standard. Detection rates were unaffected given sufficient recording time. For clinical use of the hearing-aid validation procedure, the key metric is the detection time. While this varied considerably across subjects, the observed 50% mean increase corresponds to less than 1 min of additional recording time.

For patients with bilateral cochlear implants (BiCIs), understanding a target talker in a noisy situation can be difficult. Current efforts for improving speech-in-noise understanding have focused on improving signal-to-noise ratio by using multiple microphones or signal processing, with only moderate improvements in speech understanding performance. However, BiCI users typically report having a better ear for listening which can lead to an asymmetry in speech unmasking performance. This work proposes a novel listening strategy for improving speech-in-noise understanding by combining (a) a priori knowledge of a better ear and having a BiCI user selectively attend to a target talker in that ear with (b) signal processing that delivers the target talker to the better ear and the noisy background to the opposite ear. This strategy is different from traditional noise reduction strategies because it maintains situational awareness (background sounds are delivered to the ear contralateral to the better ear) while improving speech understanding. Speech recognition performance was evaluated with and without the better ear strategy in a speech-in-noise listening test using a virtual auditory space created from individualized head-related transfer functions. Listeners showed an average improvement of 4.4 dB signal-to-noise ratio in their speech reception threshold when using the better ear strategy with no listener showing a decrement in performance. This implies that the strategy has the potential to boost speech-in-noise recognition in BiCI users and may be useful in other hearing assistance devices such as hearing aids.

Reverberation enhances music perception and is one of the most important acoustic factors in auditorium design. However, previous research on reverberant music perception has focused on young normal-hearing (YNH) listeners. Old hearing-impaired (OHI) listeners have degraded spatial auditory processing; therefore, they may perceive reverberant music differently. Two experiments were conducted examining the effects of varying reverberation on music perception for YNH and OHI listeners. Experiment 1 examined whether YNH listeners and OHI listeners prefer different amounts of reverberation for classical music listening. Symphonic excerpts were processed at a range of reverberation times using a point-source simulation. Listeners performed a paired-comparisons task in which they heard two excerpts with different reverberation times, and they indicated which they preferred. The YNH group preferred a reverberation time of 2.5 s; however, the OHI group did not demonstrate any significant preference. Experiment 2 examined whether OHI listeners are less sensitive to (e, less able to discriminate) differences in reverberation time than YNH listeners. YNH and OHI participants listened to pairs of music excerpts and indicated whether they perceived the same or different amount of reverberation. Results indicated that the ability of both groups to detect differences in reverberation time improved with increasing reverberation time difference. However, discrimination was poorer for the OHI group than for the YNH group. This suggests that OHI listeners are less sensitive to differences in reverberation when listening to music than YNH listeners, which might explain the lack of group reverberation time preferences of the OHI group.

Hearing-impaired listeners are known to have difficulties not only with understanding speech in noise but also with judging source distance and movement, and these deficits are related to perceived handicap. It is possible that the perception of spatially dynamic sounds can be improved with hearing aids (HAs), but so far this has not been investigated. In a previous study, older hearing-impaired listeners showed poorer detectability for virtual left-right (angular) and near-far (radial) source movements due to lateral interfering sounds and reverberation, respectively. In the current study, potential ways of improving these deficits with HAs were explored. Using stimuli very similar to before, detailed acoustic analyses were carried out to examine the influence of different HA algorithms for suppressing noise and reverberation on the acoustic cues previously shown to be associated with source movement detectability. For an algorithm that combined unilateral directional microphones with binaural coherence-based noise reduction and for a bilateral beamformer with binaural cue preservation, movement-induced changes in spectral coloration, signal-to-noise ratio, and direct-to-reverberant energy ratio were greater compared with no HA processing. To evaluate these two algorithms perceptually, aided measurements of angular and radial source movement detectability were performed with 20 older hearing-impaired listeners. The analyses showed that, in the presence of concurrent interfering sounds and reverberation, the bilateral beamformer could restore source movement detectability in both spatial dimensions, whereas the other algorithm only improved detectability in the near-far dimension. Together, these results provide a basis for improving the detectability of spatially dynamic sounds with HAs.

Hearing loss changes the auditory brain, sometimes maladaptively. When deprived of cochlear input, central auditory neurons become more active spontaneously and begin to respond more strongly and synchronously to better preserved sound frequencies. This spontaneous and sound-evoked central hyperactivity has been postulated to trigger tinnitus and hyperacusis, respectively. Localized hyperactivity has also been observed after long-term exposure to noise levels that do not damage the cochlea. Adult animals exposed to bands of nondamaging noise exhibited suppressed spontaneous and sound-evoked activity in the area of primary auditory cortex (A1) stimulated by the exposure band but had increased spontaneous and evoked activity in neighboring A1 areas. We hypothesized that the cortically suppressed frequencies should for some time after exposure be perceived as less loud than before (hypoacusis), whereas the hyperactivity outside of the exposure band might lead to frequency-specific hyperacusis or tinnitus. To investigate this, adult CBA/Ca mice were exposed for >2 months to 8 to 16 kHz noise at 70 or 75 dB sound pressure level and tested for hypo-/hyperacusis and tinnitus using tone and gap prepulse inhibition of the acoustic startle reflex. Auditory brainstem responses and distortion product otoacoustic emissions showed evidence of cochlear synaptopathy after exposure at 75 but not 70 dB, putting a lower bound on damaging noise levels for CBA/Ca mice. Contrary to hypothesis, neither exposure significantly shifted startle results from baseline. These negative findings nevertheless have implications for startle test methodology and for the putative role of central hyperactivity in hyperacusis and tinnitus.

Speech is an ecologically essential signal, whose processing crucially involves the subcortical nuclei of the auditory brainstem, but there are few experimental options for studying these early responses in human listeners under natural conditions. While encoding of continuous natural speech has been successfully probed in the cortex with neurophysiological tools such as electroencephalography (EEG) and magnetoencephalography, the rapidity of subcortical response components combined with unfavorable signal-to-noise ratios signal-to-noise ratio has prevented application of those methods to the brainstem. Instead, experiments have used thousands of repetitions of simple stimuli such as clicks, tone-bursts, or brief spoken syllables, with deviations from those paradigms leading to ambiguity in the neural origins of measured responses. In this study we developed and tested a new way to measure the auditory brainstem response (ABR) to ongoing, naturally uttered speech, using EEG to record from human listeners. We found a high degree of morphological similarity between the speech-derived ABRs and the standard click-evoked ABR, in particular, a preserved Wave V, the most prominent voltage peak in the standard click-evoked ABR. Because this method yields distinct peaks that recapitulate the canonical ABR, at latencies too short to originate from the cortex, the responses measured can be unambiguously determined to be subcortical in origin. The use of naturally uttered speech to measure the ABR allows the design of engaging behavioral tasks, facilitating new investigations of the potential effects of cognitive processes like language and attention on brainstem processing.

Current clinical practice in programming a cochlear implant (CI) for individuals with single-sided deafness (SSD) is to maximize the transmission of speech information via the implant, with the implicit assumption that this will also result in improved spatial-hearing abilities. However, binaural sensitivity is reduced by interaural place-of-stimulation mismatch, a likely occurrence with a standard CI frequency-to-electrode allocation table (FAT). As a step toward reducing interaural mismatch, this study investigated whether a test of interaural-time-difference (ITD) discrimination could be used to estimate the acoustic frequency yielding the best place match for a given CI electrode. ITD-discrimination performance was measured by presenting 300-ms bursts of 100-pulses-per-second electrical pulse trains to a single CI electrode and band-limited pulse trains with variable carrier frequencies to the acoustic ear. Listeners discriminated between two reference intervals (four bursts each with constant ITD) and a moving target interval (four bursts with variable ITD). For 17 out of the 26 electrodes tested across eight listeners, the function describing the relationship between ITD-discrimination performance and carrier frequency had a discernable peak where listeners achieved 70% to 100% performance. On average, this peak occurred 1.15 octaves above the CI manufacturer’s default FAT. ITD discrimination shows promise as a method of estimating the cochlear place of stimulation for a given electrode, thereby providing information to optimize the FAT for SSD-CI listeners.

For patients with profound hearing loss a cochlear implant (CI) is the only treatment today. The function of a CI depends in part of the function and survival of the remaining spiral ganglion neurons (SGN). It is well known from animal models that inner ear infusion of neurotrophic factors prevents SGN degeneration and maintains electrical responsiveness in deafened animals. The purpose with this study was to investigate the effects of a novel encapsulated cell (EC) device releasing neurotrophic factors in the deafened guinea pig. The results showed that an EC device releasing glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) implanted for four weeks in deafened guinea pigs significantly preserved the SGNs and maintained their electrical responsiveness. There was a significant difference between BDNF and GDNF in favour of GDNF. This study, demonstrating positive structural and functional effects in the deafened inner ear, suggests that an implanted EC device releasing biologically protective substances offers a feasible approach for treating progressive hearing impairment.

Animal models of tinnitus are essential for determining the underlying mechanisms and testing pharmacotherapies. However, there is doubt over the validity of current behavioural methods for detecting tinnitus. Here, we applied a stimulus paradigm widely used in a behavioural test (gap-induced inhibition of the acoustic startle reflex GPIAS) whilst recording from the auditory cortex, and showed neural response changes that mirror those found in the behavioural tests. We implanted guinea pigs (GPs) with electrocorticographic (ECoG) arrays and recorded baseline auditory cortical responses to a startling stimulus. When a gap was inserted in otherwise continuous background noise prior to the startling stimulus, there was a clear reduction in the subsequent evoked response (termed gap-induced reductions in evoked potentials; GIREP), suggestive of a neural analogue of the GPIAS test. We then unilaterally exposed guinea pigs to narrowband noise (left ear; 8-10 kHz; 1 h) at one of two different sound levels - either 105 dB SPL or 120 dB SPL - and recorded the same responses seven-to-ten weeks following the noise exposure. Significant deficits in GIREP were observed for all areas of the auditory cortex (AC) in the 120 dB-exposed GPs, but not in the 105 dB-exposed GPs. These deficits could not simply be accounted for by changes in response amplitudes. Furthermore, in the contralateral (right) caudal AC we observed a significant increase in evoked potential amplitudes across narrowband background frequencies in both 105 dB and 120 dB-exposed GPs. Taken in the context of the large body of literature that has used the behavioural test as a demonstration of the presence of tinnitus, these results are suggestive of objective neural correlates of the presence of noise-induced tinnitus and hyperacusis.

The prevalence and importance of hearing damage caused by noise levels not previously thought to cause permanent hearing impairment has become apparent in recent years. The damage to, and loss of, afferent terminals of auditory nerve fibres at the cochlear inner hair cell has been well established, but the effects of noise exposure and terminal loss on the inner hair cell are less known. Using three-dimensional structural studies in mice we have examined the consequences of afferent terminal damage on inner hair cell morphology and intracellular structure. We identified a structural phenotype in the pre-synaptic regions of these damaged hair cells that persists for four weeks after noise exposure, and demonstrates a specific dysregulation of the synaptic vesicle recycling pathway. We show evidence of a failure in regeneration of vesicles from small membrane cisterns in damaged terminals, resulting from a failure of separation of small vesicle buds from the larger cisternal membranes.

Otoacoustic emissions evoked by a click (CEOAEs) can be reduced if the evoking sound is preceded or followed by another ("suppressor") click. Studying the temporal suppression of CEOAEs can provide insights into the dynamics of cochlear nonlinearity. However, temporal suppression has never been measured in basilar-membrane (BM) motion. Thus, it remains unclear whether the characteristics of CEOAE temporal suppression are reflected in BM responses. Here we simultaneously measured ear-canal pressure and BM velocity (laser Doppler vibrometry) in response to clicks in gerbil. When the suppressor click preceded the evoking click, CEOAEs were maximally suppressed for interclick intervals (ICIs) equivalent to ~2 periods of the analyzed frequency (9-14 kHz). Maximal temporal suppression at nonzero ICIs has been previously observed in human CEOAEs. BM responses to clicks were maximally reduced when the suppressor click preceded the evoking one by ~1 period of the characteristic frequency (CF ~14 kHz). Thus, the "delayed" characteristics of CEOAE temporal suppression are reflected in BM motion, although on a different time scale. When the suppressor click followed the evoking click, CEOAEs were augmented rather than suppressed, while enhancement was not observed in BM motion at the CF. This result indicates that some aspects of CEOAE temporal suppression are intrinsic to CEOAE generation mechanisms and/or to places that are not reflected in a BM motion at a single-location.

The injectable anesthetic mixture ketamine-xylazine is commonly used for electrophysiologic experiments in laboratory animals, especially rodents. General anesthesia can induce significant changes in systemic physiology, including those that compromise neural function, thus introducing research confounds. The extent of such concerns varies by agent. Here in mice, we compared the effects of ketamine-xylazine and urethane-xylazine anesthesia on systemic physiologic parameters and the vestibular sensory evoked potential (VsEP), a tool used commonly to assess peripheral vestibular function. Urethane-xylazine anesthesia provided longer anesthesia, prolonged survival times, and less compromised respiratory and cardiovascular function, compared with ketamine-xylazine. In the absence of countermeasures, mice anesthetized with either ketamine-xylazine or urethane-xylazine showed evidence of hypoxemia and fluctuations in brain temperature, heart rate, respiration rate, and VsEP response latency. The levels of hypoxemia had no effect on VsEP response parameters over the period of study (2 to 5 h). Hypoxemia was effectively countered with O2 supplementation, which stabilized respiratory rates and improved mean survival times by 160% in mice anesthetized with ketamine-xylazine. Monitoring and controlling brain temperature reduced variation in VsEP latency. VsEP thresholds, latencies, and amplitudes did not differ between mice under ketamine-xylazine compared with urethane-xylazine when the brain temperature was held at the same set point. These findings demonstrate that urethane-xylazine provides improved systemic physiologic conditions during anesthesia in mice and may be substituted for ketamine-xylazine in studies using the VsEP to evaluate peripheral vestibular function. Such advantages may prove useful to research in other neuroscience areas and might reduce the number of animals used to achieve adequate sample sizes.

Increased acoustic startle responses (ASR), which represent reduced uncomfortable loudness level in humans, have been reported in middle-aged C57BL/6J mice with sensorineural hearing loss. Although neural plasticity changes in the central auditory system after the peripheral lesions were suggested to underlie this phenomenon, the neurological cause of exaggerated ASR is still not clear. In this study, the local field potentials and firing rates of the caudal pontine reticular nucleus (PnC), which plays a major role in the ASR pathway, were recorded in 2-month- and 6-month-old C57BL/6 J mice. Consistent with our previous studies, the amplitude of ASR increased, and the threshold of ASR decreased in the 6-month-old mice after developing 20–40 dB hearing loss. The PnC response induced by high-frequency stimuli (>20 kHz) decreased in the 6-month group, whereas the PnC response induced by low-frequency stimuli (<12 kHz) showed a significant increase in the 6-month group compared to the 2-month group. The enhancement of PnC response is similar to the ASR increase found in the 6-month-old C57 mice. Our results suggest that the high-frequency hearing loss caused an increase in PnC sensitivity in the C57 mice which may enhance ASRs.

The auditory function develops and matures after birth in many mammalian species. After hearing onset, environmental sounds exert profound and long-term effects on auditory functions. However, the effects of the acoustic environment on the functional development of the peripheral auditory system, especially the cochlear sensory hair cells, are still unclear. In the present study, we exposed mouse pups to frequency-enriched acoustic environments in postnatal days 0–14. The results indicated that the acoustic environment significantly decreased the threshold of the auditory brainstem response in a frequency-specific manner. Compared with controls, no difference was found in the number and alignment of inner and outer hair cells or in the length of hair bundles after acoustic overstimulation. The expression and function of prestin, the motor protein of outer hair cells (OHCs), were specifically increased in OHCs activated by acoustic stimulation at postnatal days 7–11. We analyzed the postnatal maturation of ribbon synapses in the hair cell areas. After acoustic stimulation, the number of ribbon synapses was closer to the mature stage than to the controls. Taken together, these data indicate that early acoustic exposure could promote the functional maturation of cochlear hair cells and the development of hearing.

Medial olivocochlear (MOC) efferent feedback is suggested to protect the ear from acoustic injury and to increase its ability to discriminate sounds against a noisy background. We investigated whether type II spiral ganglion neurons participate in the contralateral suppression of the MOC reflex. The application of ouabain to the round window of the mouse cochlea selectively induced the apoptosis of the type I spiral ganglion neurons, left the peripherin-immunopositive type II spiral ganglion neurons intact, and did not affect outer hairs, as evidenced by the maintenance of the distorted product otoacoustic emissions (DPOAEs). With the ouabain treatment, the threshold of the auditory brainstem response increased significantly and the amplitude of wave I decreased significantly in the ouabain-treated ears, consistent with the loss of type I neurons. Contralateral suppression was measured as reduction in the amplitude of the 2f 1 −f 2 DPOAEs when noise was presented to the opposite ear. Despite the loss of all the type I spiral ganglion neurons, virtually, the amplitude of the contralateral suppression was not significantly different from the control when the suppressor noise was delivered to the treated cochlea. These results are consistent with the type II spiral ganglion neurons providing the sensory input driving contralateral suppression of the MOC reflex.

PDZD7 is an important deafness gene, whose mutations are associated with syndromic and nonsyndromic hearing loss. PDZD7 contains multiple PDZ domains that are essential for organizing various proteins into protein complex. Several PDZD7-binding proteins have been identified, including usherin, ADGRV1, whirlin, harmonin, SANS, and MYO7A, all belonging to USH proteins. Here, we report the identification of novel PDZD7-binding partners through yeast two-hybrid screening using the first two PDZ domains of PDZD7 as bait. Eleven proteins were identified, most of which have not been reported as PDZD7-binding partners before. Among the identified proteins, ADGRV1, gelsolin, and β -catenin have been shown to play important roles in hearing, whereas the functions of other proteins in the inner ear remain elusive. We confirmed the expression of one candidate PDZD7-binding protein, CADM1, in the mouse inner ear and evaluated the auditory function of Cadm1 knockout mice by performing auditory brainstem response (ABR) measurement. Unexpectedly, Cadm1 knockout mice show normal hearing threshold, which might be explained by the possible compensation by its homologs that are also expressed in the inner ear. Taken together, our work identified several novel PDZD7-binding proteins, which will help us to further understand the role of PDZD7 in hearing transduction.

Damage to cochlear outer hair cells (OHCs) usually affects frequency selectivity in proportion to hearing threshold increase. However, the current clinical heuristics that attributes poor hearing performance despite near-normal auditory sensitivity to auditory neuropathy or “hidden” synaptopathy overlooks possible underlying OHC impairment. Here, we document the part played by OHCs in influencing suprathreshold auditory performance in the presence of noise in a mouse model of progressive hair cell degeneration, the CD1 strain, at postnatal day 18–30 stages when high-frequency auditory thresholds remained near-normal. Nonetheless, total loss of high-frequency distortion product otoacoustic emissions pointed to nonfunctioning basal OHCs. This “discordant profile” came with a huge low-frequency shift of masking tuning curves that plot the level of interfering sound necessary to mask the response to a probe tone, against interfering frequency. Histology revealed intense OHC hair bundle abnormalities in the basal cochlea uncharacteristically associated with OHC survival and preserved coupling with the tectorial membrane. This pattern dismisses the superficial diagnosis of “hidden” neuropathy while underpinning a disorganization of cochlear frequency mapping with optimistic high-frequency auditory thresholds perhaps because responses to high frequencies are apically shifted. The audiometric advantage of frequency transposition is offset by enhanced masking by low-frequency sounds, a finding essential for guiding rehabilitation.

Acoustic trauma is being reported to damage the auditory periphery and central system, and the compromised cortical inhibition is involved in auditory disorders, such as hyperacusis and tinnitus. Parvalbumin-containing neurons (PV neurons), a subset of GABAergic neurons, greatly shape and synchronize neural network activities. However, the change of PV neurons following acoustic trauma remains to be elucidated. The present study investigated how auditory cortical PV neurons change following unilateral 1 hour noise exposure (left ear, one octave band noise centered at 16 kHz, 116 dB SPL). Noise exposure elevated the auditory brainstem response threshold of the exposed ear when examined 7 days later. More detectable PV neurons were observed in both sides of the auditory cortex of noise-exposed rats when compared to control. The detectable PV neurons of the left auditory cortex (ipsilateral to the exposed ear) to noise exposure outnumbered those of the right auditory cortex (contralateral to the exposed ear). Quantification of Western blotted bands revealed higher expression level of PV protein in the left cortex. These findings of more active PV neurons in noise-exposed rats suggested that a compensatory mechanism might be initiated to maintain a stable state of the brain.

Spectral modulation transfer functions (SMTFs) were measured in 49 young (18–35 years of age) normal-hearing listeners. Noise carriers spanned six octaves from 200 to 12 800 Hz. Sinusoidal (on a log-amplitude scale) spectral modulation with random starting phase was superimposed on the carrier at spectral modulation frequencies of 0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 cycles/octave. Modulation detection thresholds (in dB) yielded SMTFs that were bandpass in nature, consistent with previous investigations reporting data for only a few subjects. Thresholds were notably consistent across subjects despite minimal practice. Population statistics are reported that may serve as reference data for future studies.

Recent research provides evidence for a functional role of brain oscillations for perception. For example, auditory temporal resolution seems to be linked to individual gamma frequency of auditory cortex. Individual gamma frequency not only correlates with performance in between-channel gap detection tasks but can be modulated via auditory transcranial alternating current stimulation. Modulation of individual gamma frequency is accompanied by an improvement in gap detection performance. Aging changes electrophysiological frequency components and sensory processing mechanisms. Therefore, we conducted a study to investigate the link between individual gamma frequency and gap detection performance in elderly people using auditory transcranial alternating current stimulation. In a within-subject design, nine participants were electrically stimulated with two individualized transcranial alternating current stimulation frequencies: 3 Hz above their individual gamma frequency (experimental condition) and 4 Hz below their individual gamma frequency (control condition) while they were performing a between-channel gap detection task. As expected, individual gamma frequencies correlated significantly with gap detection performance at baseline and in the experimental condition, transcranial alternating current stimulation modulated gap detection performance. In the control condition, stimulation did not modulate gap detection performance. In addition, in elderly, the effect of transcranial alternating current stimulation on auditory temporal resolution seems to be dependent on endogenous frequencies in auditory cortex: elderlies with slower individual gamma frequencies and lower auditory temporal resolution profit from auditory transcranial alternating current stimulation and show increased gap detection performance during stimulation. Our results strongly suggest individualized transcranial alternating current stimulation protocols for successful modulation of performance.