Larger Threshold Shifts Research Articles

The perception of ultrasonic vocalizations by laboratory mice following intense noise exposures.

Noise-induced hearing loss interacts with age, sex, and listening conditions to affect individuals' perception of ecologically relevant stimuli like speech. The present experiments assessed the impact of age and sex on vocalization detection by noise-exposed mice trained to detect a downsweep or complex ultrasonic vocalization in quiet or in the presence of a noise background. Daily thresholds before and following intense noise exposure were collected longitudinally and compared across several factors. All mice, regardless of age, sex, listening condition, or stimulus type showed their poorest behavioral sensitivity immediately after the noise exposure. There were varying degrees of recovery over time and across factors. Old-aged mice had greater threshold shifts and less recovery compared to middle-aged mice. Mice had larger threshold shifts and less recovery for downsweeps than for complex vocalizations. Female mice were more sensitive, had smaller post-noise shifts, and had better recovery than males. Thresholds in noise were higher and less variable than thresholds in quiet, but there were comparable shifts and recovery. In mice, as in humans, the perception of ecologically relevant stimuli suffers after an intense noise exposure, and results differ from simple tone detection findings.

How much prestin motor activity is required for normal hearing?

Prestin (SLC26A5) is a membrane-based voltage-dependent motor protein responsible for outer hair cell (OHC) somatic electromotility. Its importance for mammalian cochlear amplification has been demonstrated using mouse models lacking prestin (prestin-KO) and expressing dysfunctional prestin, prestinV499G/Y501H (499-prestin-KI). However, it is still not elucidated how prestin contributes to the mechanical amplification process in the cochlea. In this study, we characterized several prestin mouse models in which prestin activity in OHCs was variously manipulated. We found that near-normal cochlear function can be maintained even when prestin activity is significantly reduced, suggesting that the relationship between OHC electromotility and the peripheral sensitivity to sound may not be linear. This result is counterintuitive given the large threshold shifts in prestin-KO and 499-prestin-KI mice, as reported in previous studies. To reconcile these apparently opposing observations, we entertain a voltage- and turgor pressure-based cochlear amplification mechanism that requires prestin but is insensitive to significant reductions in prestin protein expression.This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam

The perception of ultrasonic signals in quiet and noise by mice exposed to noise

High-intensity noise exposures can lead to temporary or permanent increases in hearing thresholds for simple and complex stimuli. Mice produce complex signals known as ultrasonic vocalizations in a variety of behavioral contexts and it is thought these vocalizations serve a communicative function. The effects of a 2-h exposure to 8–16 kHz narrowband noise at 100 dB SPL on auditory sensitivity thresholds for two types of ultrasonic vocalizations (complex and downsweep vocalizations) in two different listening conditions (quiet and continuous 60 dB white noise) were measured. Male and female mice ranging from 100 to 1000 days old were trained to detect the vocalizations in a go/no-go operant conditioning paradigm with positive reinforcement. Each mouse participated in only one condition. Once consistent thresholds were obtained for a mouse, they were subjected to the noise exposure. Post-noise thresholds were obtained on a daily basis for up to 120 days. Similar to humans exposed to a traumatic noise, there was a lot of variability in the extent of the hearing loss following the noise exposures, with some mice experiencing large threshold shifts and other mice exhibiting only minor, temporary hearing loss. [Work supported by NIH DC016641.]

Unlearning the ABCs of Tympanometry.

Interpretation of tympanometry commonly relies on the historical convention of classifying findings according to large and arbitrary threshold shifts of tympanometric peak pressure (TPP). This convention had value for prior generations of otolaryngologists in diagnosing severe, chronic middle ear disease requiring surgical intervention but may not be well suited for the present-day evaluation of less severe disease. The existing definition of a type C curve (less than -100 daPa) is likely insensitive to detect subtle abnormalities, including some presentations of obstructive eustachian tube dysfunction. The accuracy of clinical diagnosis may be improved by reporting the absolute values of TPP and moving beyond classification according to arbitrary thresholds.

Patterns of audiometric threshold shifts from pulsatile tinnitus due to sigmoid sinus wall anomalies.

To determine the severity and nature of audiometric threshold shifts for patients with pulsatile tinnitus (PT) due to sigmoid sinus wall anomalies (SSWA). 38 patients with SSWAs and available pre-operative audiograms were examined. Low- and high-frequency pure tone averages (LF-PTA, HF-PTA) were calculated. Audiometric data were compared between affected and unaffected ears, with the interaural difference (affected-unaffected PTA) representing the change in hearing due to PT. Additionally, post-operative change was examined in 14 patients with available data. The average pre-operative air conduction (AC) LF-PTA was 17.04dB on the affected side and 11.38dB on the unaffected side (p<0.001). The mean AC HF-PTA was significantly higher on the affected side as well (16.45dB vs. 14.08dB, p=0.008). All shifts were sensorineural, with no significant air-bone gaps, and most subjects still had low-frequency thresholds in the normal range. Though the post-op change was not significant due to attrition, 5/14 patients (35.7%) had complete resolution of their pre-op interaural difference. A similar number developed a HF-PTA post-op threshold elevation in the surgical ear. PT due to SSWAs causes a mean 6dB low-frequency bone-conduction threshold elevation, and smaller high-frequency threshold shifts, due to masking. Patients with larger threshold shifts should have other potential causes of hearing loss explored. Level IV.

Vagus nerve stimulation paired with tones for tinnitus suppression: Effects on voice and hearing.

ObjectiveIn individuals with chronic tinnitus, our interest was to determine whether daily low‐level electrical stimulation of the vagus nerve paired with tones (paired‐VNSt) for tinnitus suppression had any adverse effects on motor‐speech production and physiological acoustics of sustained vowels. Similarly, we were also interested in evaluating for changes in pure‐tone thresholds, word‐recognition performance, and minimum‐masking levels. Both voice and hearing functions were measured repeatedly over a period of 1 year.Study designLongitudinal with repeated‐measures.MethodsDigitized samples of sustained frontal, midline, and back vowels (/e/, /o/, /ah/) were analyzed with computer software to quantify the degree of jitter, shimmer, and harmonic‐to‐noise ratio contained in these waveforms. Pure‐tone thresholds, monosyllabic word‐recognition performance, and MMLs were also evaluated for VNS alterations. Linear‐regression analysis was the benchmark statistic used to document change over time in voice and hearing status from a baseline condition.ResultsMost of the regression functions for the vocal samples and audiometric variables had slope values that were not significantly different from zero. Four of the nine vocal functions showed a significant improvement over time, whereas three of the pure tone regression functions at 2‐4 kHz showed some degree of decline; all changes observed were for the left ear, all were at adjacent frequencies, and all were ipsilateral to the side of VNS. However, mean pure‐tone threshold changes did not exceed 4.29 dB from baseline and therefore, would not be considered clinically significant. In some individuals, larger threshold shifts were observed. No significant regression/slope effects were observed for word‐recognition or MMLs.ConclusionQuantitative voice analysis and assessment of audiometric variables showed minimal if any evidence of adverse effects using paired‐VNSt over a treatment period of 1 year. Therefore, we conclude that paired‐VNSt is a safe tool for tinnitus abatement in humans without significant side effects.Level of evidenceLevel IV.

Long-term evidence of noise-induced permanent threshold shift in a harbor seal (Phoca vitulina).

In psychophysical studies of noise-induced hearing loss with marine mammals, exposure conditions are often titrated from levels of no effect to those that induce significant but recoverable loss of auditory sensitivity [temporary threshold shift (TTS)]. To examine TTS from mid-frequency noise, a harbor seal was exposed to a 4.1-kHz underwater tone that was incrementally increased in sound pressure level (SPL) and duration. The seal's hearing was evaluated at the exposure frequency and one-half octave higher (5.8 kHz) to identify the noise parameters associated with TTS onset. No reliable TTS was measured with increasing sound exposure level until the second exposure to a 60-s fatiguing tone of 181 dB re 1 μPa SPL (sound exposure level 199 dB re 1 μPa2s), after which an unexpectedly large threshold shift (>47 dB) was observed. While hearing at 4.1 kHz recovered within 48 h, there was a permanent threshold shift of at least 8 dB at 5.8 kHz. This hearing loss was evident for more than ten years. Furthermore, a residual threshold shift of 11 dB was detected one octave above the tonal exposure, at 8.2 kHz. This hearing loss persisted for more than two years prior to full recovery.

Neural coding of the sound envelope is changed in the inferior colliculus immediately following acoustic trauma.

Sensorineural hearing loss is often accompanied by difficulties with understanding speech in fluctuating backgrounds, suggesting that neural coding of complex sound features, such as the sound envelope, is impaired. Here, we studied how temporal and rate coding of the envelope is affected in the inferior colliculus immediately after acoustic trauma. Neural activity in response to amplitude-modulated noise was recorded from the inferior colliculus of the guinea pig, before and immediately after a 1-hr 11-kHz acoustic trauma. Units with a characteristic frequency (CF) below the trauma frequency (<11kHz) showed increased response gains, a measure for temporal coding of the sound envelope, especially at low modulation frequencies (≤128Hz). Units with a CF>11kHz, which had large acoustic trauma-induced threshold shifts, had decreased response gains to amplitude-modulated noise. Shapes of temporal modulation transfer functions shifted toward a higher proportion of low-pass shapes in low-CF units, and to less band-pass shapes in high-CF units. Furthermore, driven firing rates decreased, especially at high modulation frequencies for high-CF units. The observed changes occurred immediately following trauma and were thus a result of the immediate trauma-induced damage to the auditory system. If also present in human subjects, reduced response gains in high-frequency units could disrupt coding of consonants and consequently impair speech understanding in noisy environments. Moreover, the enhanced temporal coding by low-CF units of the low modulation frequencies could overly amplify responses to low-frequency noise, further deteriorating listening in noise.

Statistical tool to detect small hearing threshold shifts

Objective: The aim of this study is to present a new tool that can be used in the prevention of noise-induced hearing loss. Even in most countries where noise levels are well regulated, many workers are still exposed to high levels of noise and suffer from permanent threshold shifts. It is necessary to develop a new strategy to prevent such damage. Method: A statistical process control (SPC) scheme is presented that is able to detect both large and small hearing threshold shifts. Monte Carlo simulations were used to assess the performance of this hearing monitoring scheme. Different hearing threshold shifts were simulated to evaluate the performance of a variety of hearing development scenarios. Results: It is possible to detect hearing threshold shifts smaller than the standard deviation of the hearing tests performed. This means that permanent hearing threshold shifts smaller than 5 dB can be detected and acted on. Outliers can also be automatically detected and treated, increasing the robustness of the monitoring scheme. Conclusion: The proposed statistical framework can be used as an early warning indicator of noise-induced hearing loss with the aim of improving workers’ safety. Individual counteractions can be implemented, reducing the risk of further damage.

Heterostructure Source-Gated Transistors: Challenges in Design and Fabrication

Source-gated transistors (SGTs) [1, 2] use a potential barrier at the source to produce low-voltage saturation and flat saturated characteristics. This, in turn, results in excellent power efficiency and amplification performance [3-5]. Usually, SGTs are made with a Schottky source contact which acts as the current-control mechanism. These devices are easy to fabricate in a multitude of semiconductor systems, but may suffer, depending on design, from reduced dynamic range of the current above the threshold, and from significant temperature dependence of the on-current. We propose an alternative method of making SGTs, using an ohmic source contact and a bulk barrier. We call devices realised following this principle bulk unipolar barrier source-gated transistors (BUSGTs). Several strategies for realising the bulk barrier exist, which depend on the material system and fabrication process considered [6]. Here, we realise the bulk barrier at the source with a tri-layer semiconductor heterostructure (Figure 1, top). The advantages of this architecture include improved dynamic range (Figure 1, bottom) and reduced temperature dependence of drain current, as well as the usual energy and gain characteristics of SGTs. Measurement results on C70/C60/C70 n-type devices show: low hysteresis, indicating good quality interfaces; a large threshold shift due to the bulk barrier and residual charge in the heterostructure; and FET-like saturation, due to the interplay between semiconductor mobility and barrier height. A strong correlation is found between measurements and simulations using Silvaco Atlas. We discuss the benefits of such structures, and also the fabrication and design challenges associated with this type of transistor (chemistry and materials, barrier realisation, interface properties, requirements on charge carrier mobility). [1] S. D. Brotherton, Introduction to Thin Film Transistors: Physics and Technology of TFTs, Springer, 453–480, Cham (2013); [2] A. Valletta et al., J. Appl. Phys. 114 064501 (2013); [3] R. A. Sporea et al., Scientific Reports 4 4295 (2014); [4] R. A. Sporea, ULSI vs TFT V (2015); [5] R. A. Sporea et al., AA3.07, MRS Fall, Boston (2015); [6] J. M. Shannon, APL 35 (1) 63–65 (1979). Figure 1 – Top: fabricated tri-layer fullerene heterostructure, showing the position of the bulk barrier at the source; bottom: transfer characteristic of the fabricated devices, illustrating high dynamic range above threshold, low hysteresis, and significant threshold shift as due to the bulk barrier. Figure 1

Trimethyltin-induced cochlear degeneration in rat

Trimethyltin (TMT) is an occupational and environmental health hazard behaving as a potent neurotoxin known to affect the central nervous system as well as the peripheral auditory system. However, the mechanisms underlying TMT-induced ototoxicity are poorly understood. To elucidate the effects of TMT on the cochlea, a single injection of 4 or 8 mg/kg TMT was administered intraperitoneally to adult rats. The compound action potential (CAP) threshold was used to assess the functional status of the cochlea and histological techniques were used to assess the condition of the hair cells and auditory nerve fibers. TMT at 4 mg/kg produced a temporary CAP threshold elevation of 25–60 dB that recovered by 28 d post-treatment. Although there was no hair cell loss with the 4 mg/kg dose, there was a noticeable loss of auditory nerve fibers particularly beneath the inner hair cells. TMT at 8 mg/kg produced a large permanent CAP threshold shift that was greatest at the high frequencies. The CAP threshold shift was associated with the loss of outer hair cells and inner hair cells in the basal, high-frequency region of the cochlea, considerable loss of auditory nerve fibers and a significant loss of spiral ganglion neurons in the basal turn. Spiral ganglion neurons showed evidence of soma shrinkage and nuclear condensation and fragmentation, morphological features of apoptotic cell death. TMT-induced damage was greatest in the high-frequency, basal region of the cochlea and the nerve fibers beneath the inner hair cells were the most vulnerable structures.

Heterostructure Source-Gated Transistors: Challenges in Design and Fabrication

Source-gated transistors (SGTs) are usually made with a Schottky source contact which acts as the current-control mechanism. We propose an alternative method, using an ohmic source contact and a bulk barrier. Here, we realize the bulk barrier at the source with a tri-layer C70/C60/C70 heterostructure, which should lead to improved dynamic range and reduced temperature dependence of drain current, as well as the usual energy and gain characteristics of SGTs. Measurements correlate well with Silvaco Atlas simulations and show: low hysteresis, indicating good quality interfaces; a large threshold shift due to the bulk barrier and residual charge in the heterostructure; and FET-like saturation, due to the interplay between semiconductor mobility and barrier height. We discuss the benefits of such structures, and also the fabrication and design challenges associated with this type of transistor (chemistry and materials, barrier realization, interface properties, and requirements on charge carrier mobility).

Total ionizing dose response of fluorine implanted Silicon-On-Insulator buried oxide

A comparison is made of the behavior of silicon on insulator buried oxides and wet thermal oxides before and after fluorine implantation and irradiation. Before irradiation, the electrical characteristics of the thermal oxide and buried oxide are significantly different. The fluorine implantation in the smart-cut® buried oxide results in a large negative threshold shift due to the trapping of positive charges. These charges are associated with positively charged fluorine ions on implantation and are trapped at pre-existing trap sites, particularly at the bonding interface, and at additional defects caused by the ion implantation damage. This shift is absent in the wet thermal oxide. After Co60 irradiation up to 500Krad(Si), the negative flatband and threshold voltage shift in the fluorine implanted buried oxide is larger than in the unimplanted buried oxide indicating that any potential positive effect of fluorine on the passivation of interface states is more than offset by the additional trapping sites created during implantation. These results demonstrate that in the design of a transistor utmost care must be taken to prevent any fluorine being implanted into the buried oxide.

An Unorthodox Sensory Adaptation Site in the Escherichia coli Serine Chemoreceptor

The serine chemoreceptor of Escherichia coli contains four canonical methylation sites for sensory adaptation that lie near intersubunit helix interfaces of the Tsr homodimer. An unexplored fifth methylation site, E502, lies at an intrasubunit helix interface closest to the HAMP domain that controls input-output signaling in methyl-accepting chemotaxis proteins. We analyzed, with in vivo Förster resonance energy transfer (FRET) kinase assays, the serine thresholds and response cooperativities of Tsr receptors with different mutationally imposed modifications at sites 1 to 4 and/or at site 5. Tsr variants carrying E or Q at residue 502, in combination with unmodifiable D and N replacements at adaptation sites 1 to 4, underwent both methylation and demethylation/deamidation, although detection of the latter modifications required elevated intracellular levels of CheB. These Tsr variants could not mediate a chemotactic response to serine spatial gradients, demonstrating that adaptational modifications at E502 alone are not sufficient for Tsr function. Moreover, E502 is not critical for Tsr function, because only two amino acid replacements at this residue abrogated serine chemotaxis: Tsr-E502P had extreme kinase-off output and Tsr-E502I had extreme kinase-on output. These large threshold shifts are probably due to the unique HAMP-proximal location of methylation site 5. However, a methylation-mimicking glutamine at any Tsr modification site raised the serine response threshold, suggesting that all sites influence signaling by the same general mechanism, presumably through changes in packing stability of the methylation helix bundle. These findings are consistent with control of input-output signaling in Tsr through dynamic interplay of the structural stabilities of the HAMP and methylation bundles.

Mouse cochleostomy: A minimally invasive dorsal approach for modeling cochlear implantation

The murine model has been used extensively to model and study human deafness. Technical difficulty in the surgical approach due to the small size of the tympanic bulla and a robust stapedial artery has limited its application for studies of cochlear implantation and electrical stimulation. We describe a minimally traumatic, stapedial artery-sparing approach to the round window that may be used to access the mouse cochlea for acute or chronic studies of implantation and stimulation. Animal model. Fifteen C57BL6J mice were used to validate this approach. Auditory brainstem response threshold and distortion product otoacoustic emissions were obtained preoperatively and 2 weeks postoperatively to determine hearing preservation results. The approach provided excellent exposure for round-window implantation. Substantial hearing was preserved in all animals with a mean postimplantation auditory brainstem response threshold increase of 27.8 dB. Otoacoustic emissions were lost in subjects with the largest threshold shifts. Residual hearing after cochlear implantation is a determinant of success both with standard cochlear implant electrodes and with electrodes designed to optimize hearing preservation. Here, we have preserved usable hearing after implantation of C57BL6J mice, an endogenous model of human presbycusia. The murine model may become a powerful tool to assay the effects of cochlear intervention in different genetic backgrounds.

Metabolic changes in the auditory cortex in presbycusis demonstrated by MR spectroscopy

In humans, aging is accompanied by the deterioration of the hearing function — presbycusis. The major etiology for presbycusis is the loss of hair cells in the inner ear; less well known are changes in the central auditory system. Therefore, we used 1H magnetic resonance spectroscopy at 3T tomograph to examine metabolite levels in the auditory cortex of three groups of subjects: young healthy subjects less than 30years old and subjects older than 65years either with mild presbycusis corresponding to their age or with expressed presbycusis. Hearing function in all subjects was examined by pure tone audiometry (125–16000Hz). Significant differences were found in the concentrations of glutamate and N-acetylaspartate, with lower levels in aged subjects. Lactate was particularly increased in subjects with expressed presbycusis. Significant differences were not found in other metabolites, including GABA, between young and elderly subjects. The results demonstrate that the age-related changes of the inner ear are accompanied by a decrease in the excitatory neurotransmitter glutamate as well as a lactate increase in the auditory cortex that is more expressed in elderly subjects with large hearing threshold shifts.

Extended Frequency Range Hearing Thresholds and Otoacoustic Emissions in Acute Acoustic Trauma

We sought to evaluate the relative value of pure tone audiometry (PTA), extended high-frequency audiometry (EFA) and transiently evoked otoacoustic emissions (OAE) and distortion products when monitoring acute acoustic trauma (AAT). Controlled prospective clinical study. Tertiary referral center. Seventy one active duty soldiers in the same age with normal hearing Forty one soldiers suffered assault-rifle-induced acute acoustic traumas with hearing loss and tinnitus. Thirty soldiers served as a control group. Pure tone threshold changes detected by PTA and EFA, amplitude and reproducibility changes in transiently evoked OAE, distortion products, and tinnitus analysis based on a visual analog scale. Assault rifle-induced AAT caused unilateral temporary threshold shifts (TTS) in PTA and bilateral TTS in EFA. Two frequency regions with the largest threshold shifts were identified: one between 3 and 6 kHz and another between 11 and 14 kHz. The reproducibility of transiently evoked OAEs revealed changes related to the acoustic trauma in the 3- to 5-kHz frequency window. The amplitudes of the low stimulation level distortion products at 6 kHz were correlated with the audiometric AAT-induced TTS. Acute acoustic trauma-induced audiometric TTS are predominantly confined to 2 specific frequency regions. PTA and EFA are both necessary to identify the full extent of acute acoustic trauma. PTA and EFA revealed that the TTSs were correlated to with distortion product OAE amplitude shifts at 6 kHz and changes in the reproducibility of transiently evoked OAE in the 3- to 5-kHz frequency window. PTA remains the most important measurement to monitor AAT. It may be useful to complement it with EFA, focusing on the 11 to 14 kHz frequency range. If used, OAE should be analyzed in the frequency range of 3 to 6 kHz.

Characterization of Unpassivated-Solution-Processed Zinc–Tin Oxide Thin Film Transistors

We have studied the bias stress and environment stability effects of transparent bottom-gate, bottom contact spin-coated zinc–tin oxide (ZTO) thin-film transistors (TFT). Various ratios of zinc to tin (Zn:Sn= 2:1, 1:1, and 1:2) were used for TFT fabrication. The linear mobilities of the TFTs with Zn:Sn= 2:1, 1:1, and 1:2 are 2.27, 6.77, and 0.44 cm2 V-1 s-1 respectively. The on/off drain current ratio is 108 for Zn:Sn= 2:1. However, the off-current increases by more than 5 orders in 7 days, which appears to be due to the adsorption of oxygen and water molecules. The TFTs are stable under negative bias stress for more than 10,000 s, but they show a large threshold shift under positive bias stress.

Optical link ASICs for LHC upgrades

We have designed three ASICs for possible applications in a new pixel layer (insertable B-layer or IBL) for the ATLAS detector for the first phase of the LHC luminosity upgrade. The ASICs are a high-speed driver for the vertical-cavity surface-emitting laser (VCSEL), a receiver/decoder to decode the signal received at the PIN diode to extract the data and clock, and a clock multiplier to produce a higher frequency clock to serialize the data for transmission. These ASICs were designed using a 130 nm CMOS process to enhance the radiation-hardness. We have characterized the ASICs and the submission has been mostly successful. We irradiated the ASICs with 24 GeV/c protons at CERN to a dosage of 70 Mrad. We observed no significant degradation except the driver circuit in the VCSEL driver fabricated using the thick oxide process in order to provide sufficient voltage to drive a VCSEL. The degradation is due to the radiation induced large threshold shifts in the PMOS transistors used.

Radiation-hard ASICs for LHC optical data transmission

We have designed several ASICs for possible applications in a new ATLAS pixel layer for the first phase of the LHC luminosity upgrade. The ASICs include a high-speed driver for the VCSEL, a receiver/decoder to decode the signal received at the PIN diode to extract the data and clock, and a clock multiplier to produce a higher frequency clock to serialize the data for transmission. These chips were designed using a 130nm CMOS process to enhance the radiation-hardness. We have characterized the fabricated chips and the submission has been mostly successful. We irradiated the chips with 24GeV/c protons at CERN to a dosage of 70Mrad. We observed no significant degradation except the driver circuit in the VCSEL driver fabricated using the thick oxide process in order to provide sufficient voltage to drive a VCSEL. The degradation is due to the radiation induced large threshold shifts in the PMOS transistors used.