MicroRNA expression is associated with auditory dysfunction in workers exposed to ototoxic solvents and noise

This study is part of a project on early hearing dysfunction induced by combined exposure to volatile organic compounds (VOCs) and noise in occupational settings. In a previous study, 56 microRNAs were found differentially expressed in exposed workers compared to controls. Here, we analyze the statistical association of microRNA expression with audiometric hearing level (HL) and distortion product otoacoustic emission (DPOAE) level in that subset of differentially expressed microRNAs. The highest negative correlations were found; for HL, with miR-195-5p and miR-122-5p, and, for DPOAEs, with miR-92b-5p and miR-206. The homozygous (mut) and heterozygous (het) variants of the gene hOGG1 were found disadvantaged with respect to the wild-type (wt), as regards the risk of hearing impairment due to exposure to VOCs. An unsupervised artificial neural network (auto contractive map) was also used to detect and show, using graph analysis, the hidden connections between the explored variables. These findings may contribute to the formulation of mechanistic hypotheses about hearing damage due to co-exposure to noise and ototoxic solvents

Association between hearing sensitivity and dopamine transporter availability in Parkinson's disease

In a previous study, we observed: significant hearing function impairment, assessed with pure tone audiometry and distortion product otoacoustic emissions, in patients with Parkinson's disease, compared with a matched control group, and lateralization of the hearing dysfunction, worse on the side affected by more pronounced Parkinson's disease motor symptoms. This study investigates the association between the basal ganglia dopamine transporter availability and the hearing function in Parkinson's disease patients, focusing also on the lateralization of both dysfunctions, with respect to that of the motor symptoms, and introducing a further distinction between patients with left-sided and right-sided predominant motor symptoms. Patients with right-handed Parkinson's disease with a recent estimation of 123I-FP-CIT striatal uptake were audiologically tested with pure tone audiometry and distortion product otoacoustic emissions. Thirty-nine patients were included in the study. A statistically significant association was found, in the left-side predominant group only, between the distortion product otoacoustic emission levels and the contralateral dopamine transporter availability, and between the hearing threshold and the dopamine transporter availability difference between the ipsi- and the contralateral sides. The hearing impairment lateralization correlated to the motor symptom asymmetry was found significant only in the left-side predominant patients. The association between hearing function and basal ganglia dopamine transporter availability supports the hypothesis that the peripheral hearing function decline associated with dopamine depletion is involved in Parkinson's disease development, with a significant difference between patients with left- and right-sided predominant motor symptoms. These findings also suggest that peripheral hearing function evaluation and its lateralization could be key elements for subtyping the disease

Prenatal and Postnatal Serum PCB Concentrations and Cochlear Function in Children at 45 Months of Age

Background: Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively. Objectives: Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs. Methods: A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders. Results: Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: –2.6, –0.5; p = 0.003). Conclusions: In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months. Citation: Jusko TA, Sisto R, Iosif AM, Moleti A, Wimmerová S, Lancz K, Tihányi J, Šovčíková E, Drobná B, Palkovičová L, Jurečková D, Thevenet-Morrison K, Verner MA, Sonneborn D, Hertz-Picciotto I, Trnovec T. 2014. Prenatal and postnatal serum PCB concentrations and cochlear function in children at 45 months of age. Environ Health Perspect 122:1246–1252; http://dx.doi.org/10.1289/ehp.130747

Objective measurement of cochlear tuning factor by means of time-frequency analysis of oto-acoustic emissions

A new technique is proposed for the objective estimate of cochlear tuning, starting from measurements of the delay function of Stimulus Frequency (SF) and Transiently Evoked (TE) Otoacoustic Emissions (OAEs). The technique is quick and reliable, also in not cooperating subjects, while the psychoacoustic tuning measurements are time consuming and based on a large number of assumptions. It is well known that OAEs originate from two main backscattering mechanisms: coherent reflection and nonlinear wave-fixed distortion. The main TEO-AE and SFOAE sources are supposed to be linear reflection from the peak region, due to randomly distributed roughness. Recent experiments found evidence of OAE sources more basally located with respect to the CP (characteristic place) on the basilar membrane (BM). The origin of the basal sources is due to the multiple-peak nature of the coherent local reflectivity function generated by the roughness. The OAE components generated at different places of the BM can be effectively separated in the time-frequency domain, being characterized by different phase-gradient delay. A time-frequency technique was proposed to identify the curved time-frequency region corresponding to single-reflection SFOAE and TEOAE components, to get, for each frequency, a weighted average of the delay over this region, weighted by the square of the wavelet coefficient. This average delay is assumed to scale as the square root of the tuning factor. The estimated spectral tuning values turned out to decrease significantly with increasing stimulus level, confirming that at high stimulus levels a saturation process occurs in which a widening of the BM excitation patterns takes place. This increase of the BM response width increases the relative importance of the shorter-delay more basal peaks of the reflectance and, consequently, a reduction of the average delay. The proposed technique is based on the idea that a smooth relation exists between the average delay and the BM tuning, which is correctly exploited to get reliable and stable tuning estimates only if: 1) multiple reflections are filtered out, and 2) a weighted average of the delay is considered instead of a single delay value associated with the most intense of the OAE components, which is that picked up by standard measurements of the phase-gradient delay

Does the "reticular lamina nonlinearity" contribute to the basal DPOAE source?

The spatial extent of the cochlear region that actually contributes to the DPOAE signal measured in the ear canal may be evaluated experimentally using interference tones or computed numerically using nonlinear cochlear models. A nonlinear transmission-line cochlear model is used in this study to evaluate whether the recently reported nonlinear behavior of the reticular lamina (RL) over a wide basal region may be associated with generation of a significant distortion product otoacoustic emission (DPOAE) component. A two-degrees-of-freedom 1-D nonlinear model was used as discussed by Sisto et al. (2019), in which each local element consists of two coupled oscillators, roughly representing the basilar membrane (BM) and the RL. In this model, the RL shows a strongly nonlinear response over a wide region basal to the characteristic place, whereas the BM response is linear outside the narrow peak region. Such a model may be considered as that using the minimal number of degrees of freedom necessary to separately predict the motion of the BM and RL, while preserving important cochlear symmetries, such as the zero-crossing invariance of the impulse response. In the numerical simulations, the RL nonlinearity generates indeed a large intracochlear distortion product source, extended down to very basal cochlear regions. Nevertheless, due to the weak and indirect coupling between the RL motion and the differential fluid pressure in the basal part of the traveling wave path, no significant contribution from this mechanism is predicted by the model to the generation of the DPOAE signal that is eventually measured in the ear canal

DPOAEs evoked by different stimulus paradigms in a fully nonlinear cochlear model

The DPOAE generation is a consequence of the intrinsically nonlinear nature of the cochlear dynamics. Different stimulus paradigms have been proposed for using DPOAE measurements as a diagnostic test of the hearing function. In particular, Kummer et al. [1] proposed a method for measuring the hearing threshold by extrapolating the growth rates of the linear DPOAE response at zero response magnitude, and defining this level as the best estimate of the audiometric threshold level. This method requires the so called “scissors” paradigm for evoking DPOAE. The scissors paradigm is considered capable of approximately maximizing the DPOAE response at any saturation regime, in all frequency ranges. In the scissors paradigm the L2 stimulus grows much faster than L1. A higher L1 level is generally needed because, in the “overlap” nonlinear distortion generation place, x(f2), the basilar membrane (BM) response to f2 is fully resonant whereas that to f1 is not. On the other hand, the nonlinearity of the BM response implies that the “advantage” of the f2 component decreases with increasing stimulus level, as the bandwidth of the response also increases. Different growth rates are obviously associated to DPOAE evoked by different paradigms. In addition, it is quite difficult to interpret the DPOAE growth curves when complex protocols are used to evoke them. In this work, a nonlinear non-local cochlear model is proposed to simulate otoacoustic emissions. The presence of strong nonlinearity, as a physical non-perturbative property of the system, requires a time domain solution of the equations representing the cochlea from a micromechanical point of view. The cochlear equations are solved in time domain by means of the state space variables mathematical formalism [2]. The model parameter space has been explored in order to generate DPOAE levels and growth rates compatible with experimental data on human subjects. The main properties of the DPOAE generated by the different paradigms have been reproduced. In particular, the “scissors” paradigm was able to maximize the DP amplitude at each L2 stimulus level, in agreement with the experimental evidence. The proposed model represents a useful tool for studying OAE evoked by complex protocols in strongly nonlinear regime

On the frequency dependence of the otoacoustic emission latency in hypoacoustic and normal ears

Experimental measurements of the otoacoustic emission (OAE) latency of adult subjects have been obtained, as a function of frequency, by means of wavelet time-frequency analysis based on the iterative application of filter banks. The results are in agreement with previous OAE latency measurements by Tognola et al. [Hear. Res. 106, 112-122 (1997)], as regards both the latency values and the frequency dependence, and seem to be incompatible with the steep I/f law that is predicted by scale-invariant full cochlear models. The latency-frequency relationship has been best fitted to a linear function of the cochlear physical distance, using the Greenwood map, and to an exponential function of the cochlear distance, for comparison with derived band ABR latency measurements. Two sets of ears [94 audiometrically normal and 42 impaired with high-frequency (f > 3 kHz) hearing loss] have been separately analyzed. Significantly larger average latencies were found in the impaired ears in the mid-frequency range. Theoretical implications of these findings on the transmission of the traveling wave are discussed. (C) 2002 Acoustical Society of America

Considerations on balloon-borne far infrared telescopes

The design of a telescope devoted to infrared and millimetric differential measurements is described. The optics are well corrected for aberrations, either in the on-axis or in the off-axis configurations, for tilt angles ∼1° of the secondary mirror. The diffraction pattern at large angles is calculated as a function of the surface quality and the in flight background at ballon altitude is estimated