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Journal: Journal of the Association for Research in Otolaryngology : JARO

28

Meniere’s disease is characterized by sporadic episodes of vertigo, nystagmus, fluctuating sensorineural hearing loss, tinnitus and aural pressure. Since Meniere’s disease can affect different regions of the vestibular labyrinth, we investigated if electrical vestibular stimulation (EVS) which excites the entire vestibular labyrinth may be useful to reveal patchy endorgan pathology. We recorded three-dimensional electrically evoked vestibulo-ocular reflex (eVOR) to transient EVS using bilateral, bipolar 100-ms current steps at intensities of 0.9, 2.5, 5.0, 7.5 and 10.0 mA with dual-search coils in 12 unilateral Meniere’s patients. Their results were compared to 17 normal subjects. Normal eVOR had tonic and phasic spatiotemporal properties best described by the torsional component, which was four times larger than horizontal and vertical components. At EVS onset and offset of 8.9 ms latency, there were phasic eVOR initiation (M = 1,267 °/s(2)) and cessation (M = -1,675 °/s(2)) acceleration pulses, whereas during the constant portion of the EVS, there was a maintained tonic eVOR (M = 9.1 °/s) at 10 mA. However in Meniere’s disease, whilst latency of EVS onset and offset was normal at 9.0 ms, phasic eVOR initiation (M = 1,720 °/s(2)) and cessation (M = -2,523 °/s(2)) were enlarged at 10 mA. The initiation profile was a bimodal response, whilst the cessation profile frequently did not return to baseline. The tonic eVOR (M = 20.5 °/s) exhibited a ramped enhancement of about twice normal at 10 mA. Tonic eVOR enhancement was present for EVS >0.9 mA and disproportionately enhanced the torsional, vertical and horizontal components. These eVOR abnormalities may be a diagnostic indicator of Meniere’s disease and may explain the vertigo attacks in the presence of declining mechanically evoked vestibular responses.

Concepts: Vestibular system, Vestibulo-ocular reflex, Ear, Tinnitus, Ménière's disease, Pathologic nystagmus, Organ of Corti, Endolymph

28

Young adults with normal hearing (YNH) can improve their sensitivity to basic acoustic features with practice. However, it is not known to what extent the influence of the same training regimen differs between YNH listeners and older listeners with hearing impairment (OHI)-the largest population seeking treatment in audiology clinics. To examine this issue, we trained OHI listeners on a basic auditory task (spectral modulation detection) using a training regimen previously administered to YNH listeners (∼1 h/session for seven sessions on a single condition). For the trained conditions on which pretraining performance was not already at asymptote, the YNH listeners who received training learned more than matched controls who received none, but that learning did not generalize to any untrained spectral modulation frequency. In contrast, the OHI-trained listeners and controls learned similar amounts on the trained condition, implying no effect of the training itself. However, surprisingly the OHI-trained listeners improved over the training phase and on an untrained spectral modulation frequency. These population differences suggest that learning consolidated more slowly, and that training modified an aspect of processing that had broader tuning to spectral modulation frequency, in OHI than YNH listeners. More generally, these results demonstrate that conclusions about perceptual learning that come from examination of one population do not necessarily apply to another.

Concepts: Psychology, Skill, Hearing impairment, Training, Sense, Phase, Learning, Audiogram

27

Users of bilateral cochlear implants (CIs) experience difficulties localizing sounds in reverberant rooms, even in rooms where normal-hearing listeners would hardly notice the reverberation. We measured the localization ability of seven bilateral CI users listening with their own devices in anechoic space and in a simulated reverberant room. To determine factors affecting performance in reverberant space we measured the sensitivity to interaural time differences (ITDs), interaural level differences (ILDs), and forward masking in the same participants using direct computer control of the electric stimulation in their CIs. Localization performance, quantified by the coefficient of determination r (2) and the root mean squared error, was significantly worse in the reverberant room than in anechoic conditions. Localization performance in the anechoic room, expressed as r (2), was best predicted by subject’s sensitivity to ILDs. However, the decrease in localization performance caused by reverberation was better predicted by the sensitivity to envelope ITDs measured on single electrode pairs, with a correlation coefficient of 0.92. The CI users who were highly sensitive to envelope ITDs also better maintained their localization ability in reverberant space. Results in the forward masking task added only marginally to the predictions of localization performance in both environments. The results indicate that envelope ITDs provided by CI processors support localization in reverberant space. Thus, methods that improve perceptual access to envelope ITDs could help improve localization with bilateral CIs in everyday listening situations.

Concepts: Prediction, Futurology, Prophecy, Pearson product-moment correlation coefficient, Sound, Mean squared error, Neuroprosthetics, Interaural time difference

23

Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products. Natural products such as herbal supplements are easily accessible and commonly used in the practice of traditional eastern and alternative medicine. Using the zebrafish lateral line, we screened a natural products library to identify potential ototoxins. We found that the flavonoids quercetin and kaempferol, both from the Gingko biloba plant, demonstrated significant ototoxicity, killing up to 30 % of lateral line hair cells. We then examined a third Ginkgo flavonoid, isorhamnetin, and found similar levels of ototoxicity. After flavonoid treatment, surviving hair cells demonstrated reduced uptake of the vital dye FM 1-43FX, suggesting that the health of the remaining hair cells was compromised. We then asked if these flavonoids enter hair cells through the mechanotransduction channel, which is the site of entry for many known ototoxins. High extracellular calcium or the quinoline derivative E6 berbamine significantly protected hair cells from flavonoid damage, implicating the transduction channel as a site of flavonoid uptake. Since known ototoxins activate cellular stress responses, we asked if reactive oxygen species were necessary for flavonoid ototoxicity. Co-treatment with the antioxidant D-methionine significantly protected hair cells from each flavonoid, suggesting that antioxidant therapy could prevent hair cell loss. How these products affect mammalian hair cells is still an open question and will be the target of future experiments. However, this research demonstrates the potential for ototoxic damage caused by unregulated herbal supplements and suggests that further supplement characterization is warranted.

Concepts: Antioxidant, Chemotherapy, Flavonoid, Cisplatin, Ginkgo biloba, Flavonols, Ginkgo, Living fossil

4

Speech intelligibility is currently measured by scoring how well a person can identify a speech signal. The results of such behavioral measures reflect neural processing of the speech signal, but are also influenced by language processing, motivation, and memory. Very often, electrophysiological measures of hearing give insight in the neural processing of sound. However, in most methods, non-speech stimuli are used, making it hard to relate the results to behavioral measures of speech intelligibility. The use of natural running speech as a stimulus in electrophysiological measures of hearing is a paradigm shift which allows to bridge the gap between behavioral and electrophysiological measures. Here, by decoding the speech envelope from the electroencephalogram, and correlating it with the stimulus envelope, we demonstrate an electrophysiological measure of neural processing of running speech. We show that behaviorally measured speech intelligibility is strongly correlated with our electrophysiological measure. Our results pave the way towards an objective and automatic way of assessing neural processing of speech presented through auditory prostheses, reducing confounds such as attention and cognitive capabilities. We anticipate that our electrophysiological measure will allow better differential diagnosis of the auditory system, and will allow the development of closed-loop auditory prostheses that automatically adapt to individual users.

Concepts: Psychology, Brain, Neuroscience, Auditory system, Behavior, Human behavior, Sound, Differential diagnosis

4

The objective of this large population-based cross-sectional study was to evaluate the association between smoking, passive smoking, alcohol consumption, and hearing loss. The study sample was a subset of the UK Biobank Resource, 164,770 adults aged between 40 and 69 years who completed a speech-in-noise hearing test (the Digit Triplet Test). Hearing loss was defined as speech recognition in noise in the better ear poorer than 2 standard deviations below the mean with reference to young normally hearing listeners. In multiple logistic regression controlling for potential confounders, current smokers were more likely to have a hearing loss than non-smokers (odds ratio (OR) 1.15, 95 % confidence interval (CI) 1.09-1.21). Among non-smokers, those who reported passive exposure to tobacco smoke were more likely to have a hearing loss (OR 1.28, 95 %CI 1.21-1.35). For both smoking and passive smoking, there was evidence of a dose-response effect. Those who consume alcohol were less likely to have a hearing loss than lifetime teetotalers. The association was similar across three levels of consumption by volume of alcohol (lightest 25 %, OR 0.61, 95 %CI 0.57-0.65; middle 50 % OR 0.62, 95 %CI 0.58-0.66; heaviest 25 % OR 0.65, 95 %CI 0.61-0.70). The results suggest that lifestyle factors may moderate the risk of hearing loss. Alcohol consumption was associated with a protective effect. Quitting or reducing smoking and avoiding passive exposure to tobacco smoke may also help prevent or moderate age-related hearing loss.

Concepts: Regression analysis, Lung cancer, Smoking, Tobacco, Tobacco smoking, Cigarette, Nicotine, Normal distribution

3

We recorded responses of the gerbil basilar membrane (BM) to wideband tone complexes. The intensity of one component was varied and the effects on the amplitude and phase of the others were assessed. This suppression paradigm enabled us to vary probe frequency and suppressor frequency independently, allowing the use of simple scaling arguments to analyze the spatial buildup of the nonlinear interaction between traveling waves. Most suppressors had the same effects on probe amplitude and phase as did wideband intensity increments. The main exception were suppressors above the characteristic frequency (CF) of the recording location, for which the frequency range of most affected probes was not constant, but shifted upward with suppressor frequency. BM displacement reliably predicted the effectiveness of low-side suppressors, but not high-side suppressors. We found “anti-suppression” of probes well below CF, i.e., suppressor-induced enhancement of probe response amplitude. Large (>1 cycle) phase effects occurred for above-CF probes. Phase shifts varied nonmonotonically, but systematically, with suppressor level, probe frequency, and suppressor frequency, reconciling apparent discrepancies in the literature. The analysis of spatial buildup revealed an accumulation of local effects on the propagation of the traveling wave, with larger BM displacement reducing the local forward gain. The propagation speed of the wave was also affected. With larger BM displacement, the basal portion of the wave slowed down, while the apical part sped up. This framework of spatial buildup of local effects unifies the widely different effects of overall intensity, low-side suppressors, and high-side suppressors on BM responses.

Concepts: Quantum mechanics, Optics, Wave, Phase, Frequency, Wavelength, Sound, Phase velocity

2

Despite the widespread treatment of motion sickness symptoms using drugs and the involvement of the vestibular system in motion sickness, little is known about the effects of anti-motion sickness drugs on vestibular perception. In particular, the impact of oral promethazine, widely used for treating motion sickness, on vestibular perceptual thresholds has not previously been quantified. We examined whether promethazine (25 mg) alters vestibular perceptual thresholds in a counterbalanced, double-blind, within-subject study. Thresholds were determined using a direction recognition task (left vs. right) for whole-body yaw rotation, y-translation (interaural), and roll tilt passive, self-motions. Roll tilt thresholds were 31 % higher after ingestion of promethazine (P = 0.005). There were no statistically significant changes in yaw rotation and y-translation thresholds. This worsening of precision could have functional implications, e.g., during driving, bicycling, and piloting tasks. Differing results from some past studies of promethazine on the vestibulo-ocular reflex emphasize the need to study motion perception in addition to motor responses.

Concepts: Psychology, Cognition, Perception, Vestibular system, Vestibulo-ocular reflex, Rotation matrix, Reflex, Motion sickness

1

Sound intensity is a key feature of auditory signals. A profound understanding of cortical processing of this feature is therefore highly desirable. This study investigates whether cortical functional near-infrared spectroscopy (fNIRS) signals reflect sound intensity changes and where on the brain cortex maximal intensity-dependent activations are located. The fNIRS technique is particularly suitable for this kind of hearing study, as it runs silently. Twenty-three normal hearing subjects were included and actively participated in a counterbalanced block design task. Four intensity levels of a modulated noise stimulus with long-term spectrum and modulation characteristics similar to speech were applied, evenly spaced from 15 to 90 dB SPL. Signals from auditory processing cortical fields were derived from a montage of 16 optodes on each side of the head. Results showed that fNIRS responses originating from auditory processing areas are highly dependent on sound intensity level: higher stimulation levels led to higher concentration changes. Caudal and rostral channels showed different waveform morphologies, reflecting specific cortical signal processing of the stimulus. Channels overlying the supramarginal and caudal superior temporal gyrus evoked a phasic response, whereas channels over Broca’s area showed a broad tonic pattern. This data set can serve as a foundation for future auditory fNIRS research to develop the technique as a hearing assessment tool in the normal hearing and hearing-impaired populations.

Concepts: Brain, Cerebral cortex, Superior temporal gyrus, Wernicke's area, Acoustics, Sound, Sound intensity, Sound intensity level

1

Gentamicin is an aminoglycoside antibiotic used to treat gram-negative bacterial infections. Treatment with this antibiotic carries the potential for adverse side effects, including ototoxicity and nephrotoxicity. Ototoxic effects are at least in part a consequence of oxidative stress, and various antioxidants have been used to attenuate gentamicin-induced hair cell death and hearing loss. Here, a combination of nutrients previously shown to reduce oxidative stress in the hair cells and attenuate hearing loss after other insults was evaluated for potential protection against gentamicin-induced ototoxicity. Guinea pigs were maintained on a nutritionally complete standard laboratory animal diet or a diet supplemented with β-carotene, vitamins C and E, and magnesium. Three diets with iterative increases in nutrient levels were screened; the final diet selected for study use was one that produced statistically reliable increases in plasma levels of vitamins C and E and magnesium. In two separate studies, significant decreases in gentamicin-induced hearing loss at frequencies including 12 kHz and below were observed, with less benefit at the higher frequencies. Consistent with the functional protection, robust protection of both the inner and outer hair cell populations was observed, with protection largely in the upper half of the cochlea. Protection was independently assessed in two different laboratories, using two different strains of guinea pigs. Additional in vitro tests did not reveal any decrease in antimicrobial activity with nutrient additives. Currently, there are no FDA-approved treatments for the prevention of gentamicin-induced ototoxicity. The current data provide a rationale for continued investigations regarding translation to human patients.

Concepts: Bacteria, Nutrition, Microbiology, Nitrogen, Cochlea, Vitamin C, Hair cell, Organ of Corti