Enhanced Vestibulo-ocular Reflex to Electrical Vestibular Stimulation in Meniere’s Disease

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 °/s²) and cessation (M = −1,675 °/s²) 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 °/s²) and cessation (M = −2,523 °/s²) 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.     

Temporal Resolution of the Normal Ear in Listeners with Unilateral Hearing Impairment

Unilateral hearing loss (UHL) leads to an imbalanced input to the brain and results in cortical reorganization. In listeners with unilateral impairments, while the perceptual deficits associated with the impaired ear are well documented, less is known regarding the auditory processing in the unimpaired, clinically normal ear. It is commonly accepted that perceptual consequences are unlikely to occur in the normal ear for listeners with UHL. This study investigated whether the temporal resolution in the normal-hearing (NH) ear of listeners with long-standing UHL is similar to those in listeners with NH. Temporal resolution was assayed via measuring gap detection thresholds (GDTs) in within- and between-channel paradigms. GDTs were assessed in the normal ear of adults with long-standing, severe-to-profound UHL (N = 13) and age-matched, NH listeners (N = 22) at two presentation levels (30 and 55 dB sensation level). Analysis indicated that within-channel GDTs for listeners with UHL were not significantly different than those for the NH subject group, but the between-channel GDTs for listeners with UHL were poorer (by greater than a factor of 2) than those for the listeners with NH. The hearing thresholds in the normal or impaired ears were not associated with the elevated between-channel GDTs for listeners with UHL. Contrary to the common assumption that auditory processing capabilities are preserved for the normal ear in listeners with UHL, the current study demonstrated that a long-standing unilateral hearing impairment may adversely affect auditory perception—temporal resolution—in the clinically normal ear. From a translational perspective, these findings imply that the temporal processing deficits in the unimpaired ear of listeners with unilateral hearing impairments may contribute to their overall auditory perceptual difficulties.     

Plasticity in the adult human central auditory system: evidence from late-onset profound unilateral deafness.

Experience-related changes in central nervous system (CNS) activity have been observed in the adult brain of many mammalian species, including humans. In humans, late-onset profound unilateral deafness creates an opportunity to study plasticity in the adult CNS consequent to monaural auditory deprivation. CNS activity was assessed by measuring long-latency auditory evoked potentials (AEPs) recorded from teens and adults with late-onset (post-childhood) profound unilateral deafness. Compared to monaurally stimulated normal-hearing subjects, the AEPs recorded from central electrode sites located over auditory cortical areas showed significant increases in inter-hemispheric waveform cross-correlation coefficients, and in inter-hemispheric AEP peak amplitude correlations. These increases provide evidence of substantial changes from the normal pattern of asymmetrical (contralateral > ipsilateral amplitude) and asynchronous (contralateral earlier than ipsilateral) central auditory system activation in the normal-hearing population to a much more symmetrical and synchronous activation in the unilaterally deaf. These cross-sectional analyses of AEP data recorded from the unilaterally deaf also suggest that the changes in cortical activity occur gradually and continue for at least 2 years after the onset of hearing loss. Analyses of peak amplitude correlations suggest that the increased inter-hemispheric symmetry may be a consequence of changes in the generators producing the N (approximately 100 ms peak latency) potential. These experience-related changes in central auditory system activity following late-onset profound unilateral deafness thus provide evidence of the presence and the time course of auditory system plasticity in the adult brain.     

Auditory Brainstem Response at the Detection Limit

Specific predictions regarding the level dependence of auditory evoked responses near the detection limit were made in a companion modeling study (Lütkenhöner, J Assoc Res Otolaryngol 9:102–121, 2008). Here, these predictions are experimentally tested for auditory brainstem responses (ABR) to Gaussian-shaped 4-kHz tone pulses (full width at half maximum = 0.5 ms) that were presented at sound levels close to the subjective threshold. In the average of over about one million stimulus repetitions (repetition period = 16 ms), the amplitude of ABR wave V showed a smooth transition from a proportional to a logarithmic growth with increasing sound intensity. The latter type of growth corresponds to a linear increase with respect to sound level measured in decibels. Alternatively, the ABR amplitude near the detection limit may be considered a linear function of sound pressure, although—according to the model—this is only an approximation. Data and model are consistent with the view that a sensory threshold does not exist for the auditory modality, in accordance with signal detection theory. Even so, the model may be used to define a quasithreshold that is comparable to the subjective threshold.     

Differential Ear Effects of Profound Unilateral Deafness on the Adult Human Central Auditory System

This study investigates the effects of profound acquired unilateral deafness on the adult human central auditory system by analyzing long-latency auditory evoked potentials (AEPs) with dipole source modeling methods. AEPs, elicited by clicks presented to the intact ear in 19 adult subjects with profound unilateral deafness and monaurally to each ear in eight adult normal-hearing controls, were recorded with a 31-channel system. The responses in the 70–210 ms time window, encompassing the N_1b/P₂ and Ta/Tb components of the AEPs, were modeled by a vertically and a laterally oriented dipole source in each hemisphere. Peak latencies and amplitudes of the major components of the dipole waveforms were measured in the hemispheres ipsilateral and contralateral to the stimulated ear. The normal-hearing subjects showed significant ipsilateral–contralateral latency and amplitude differences, with contralateral source activities that were typically larger and peaked earlier than the ipsilateral activities. In addition, the ipsilateral–contralateral amplitude differences from monaural presentation were similar for left and for right ear stimulation. For unilaterally deaf subjects, the previously reported reduction in ipsilateral–contralateral amplitude differences based on scalp waveforms was also observed in the dipole source waveforms. However, analysis of the source dipole activity demonstrated that the reduced inter-hemispheric amplitude differences were ear dependent. Specifically, these changes were found only in those subjects affected by profound left ear unilateral deafness.     

A Genome-Wide Association Study of Chronic Otitis Media with Effusion and Recurrent Otitis Media Identifies a Novel Susceptibility Locus on Chromosome 2

Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have been shown to be heritable, but candidate gene and linkage studies to date have been equivocal. Our aim was to identify genetic susceptibility factors using a genome-wide association study (GWAS). We genotyped 602 subjects from 143 families with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip (324,748 SNPs). We carried out the GWAS scan and imputed SNPs at the regions with the most significant associations. Replication genotyping in an independent family-based sample was conducted for 53 SNPs: the 41 most significant SNPs with P < 10⁻⁴ and 12 imputed SNPs with P < 10⁻⁴ on chromosome 15 (near the strongest signal). We replicated the association of rs10497394 (GWAS discovery P = 1.30 × 10⁻⁵) on chromosome 2 in the independent otitis media population (P = 4.7 × 10⁻⁵; meta-analysis P = 1.52 × 10⁻⁸). Three additional SNPs had replication P values < 0.10. Two were on chromosome 15q26.1 including rs1110060, the strongest association with COME/ROM in the primary GWAS (P = 3.4 ×10⁻⁷) in KIF7 intron 7 (P = 0.072), and rs10775247, a non-synonymous SNP in TICRR exon 2 (P = 0.075). The third SNP rs386057 was on chromosome 5 in TPPP intron 1 (P = 0.045). We have performed the first GWAS of COME/ROM and have identified a SNP rs10497394 on chromosome 2 is significantly associated with COME/ROM susceptibility. This SNP is within a 537 kb intergenic region, bordered by CDCA7 and SP3. The genomic and functional significance of this newly identified locus in COME/ROM pathogenesis requires additional investigation.     

Gentamicin is Primarily Localized in Vestibular Type I Hair Cells after Intratympanic Administration

Intratympanic (IT) gentamicin injections are effective in the control of episodic vertigo due to Ménière’s disease. Histological studies in animals have found that the loss of type I vestibular hair cells far exceeds that of type II cells after IT gentamicin treatment. The objective of this study was to determine whether this selective toxicity for type I hair cells might be due to selective concentration of the drug by these cells. Gentamicin was localized within the vestibular epithelium by both direct and indirect methods. Gentamicin conjugated to Texas Red® was used as a direct tracer, and anti-gentamicin antibody provided an indirect means of localization. Conjugated or unconjugated gentamicin was injected into the left tympanic space of chinchillas. The animals were killed and fixed 1 or 3 weeks post-treatment. Confocal fluorescence microscopy was used to determine the localization of gentamicin in semicircular canal cristae. Results from the animals killed within 1 week of administration showed that numerous type I hair cells still remained throughout the epithelium. The mean intensity in grayscale units (0–255) of anti-gentamicin labeling for type I hair cells was 28.14 (95% CI 24.60–31.69), for type II hair cells was 17.09 (14.99–19.20), and for support cells was 5.35 (5.34–5.46; p < 0.001, ANOVA). Anti-gentamicin antibody labeling appeared in the majority of type I hair cells throughout their cytoplasm, but with greater intensity at the apex (p < 0.001). Intensity of fluorescence with Texas-Red conjugated gentamicin was 25.38 (22.83–27.94) in type I hair cells, 15.60 (14.73–16.48) in type II cells, and 12.62 (12.06–13.17) in support cells (p < 0.001, ANOVA). These results suggest that type I hair cells are more susceptible to gentamicin because they more avidly take up or retain the drug in the early period after administration.     

Unilateral Adaptation of the Human Angular Vestibulo-Ocular Reflex

A recent study showed that the angular vestibulo-ocular reflex (VOR) can be better adaptively increased using an incremental retinal image velocity error signal compared with a conventional constant large velocity-gain demand (×2). This finding has important implications for vestibular rehabilitation that seeks to improve the VOR response after injury. However, a large portion of vestibular patients have unilateral vestibular hypofunction, and training that raises their VOR response during rotations to both the ipsilesional and contralesional side is not usually ideal. We sought to determine if the vestibular response to one side could selectively be increased without affecting the contralateral response. We tested nine subjects with normal vestibular function. Using the scleral search coil and head impulse techniques, we measured the active and passive VOR gain (eye velocity / head velocity) before and after unilateral incremental VOR adaptation training, consisting of self-generated (active) head impulses, which lasted ∼15 min. The head impulses consisted of rapid, horizontal head rotations with peak-amplitude 15 ^o, peak-velocity 150 ^o/s and peak-acceleration 3,000 ^o/s². The VOR gain towards the adapting side increased after training from 0.92 ± 0.18 to 1.11 ± 0.22 (+22.7 ± 20.2 %) during active head impulses and from 0.91 ± 0.15 to 1.01 ± 0.17 (+11.3 ± 7.5 %) during passive head impulses. During active impulses, the VOR gain towards the non-adapting side also increased by ∼8 %, though this increase was ∼70 % less than to the adapting side. A similar increase did not occur during passive impulses. This study shows that unilateral vestibular adaptation is possible in humans with a normal VOR; unilateral incremental VOR adaptation may have a role in vestibular rehabilitation. The increase in passive VOR gain after active head impulse adaptation suggests that the training effect is robust.     

Hyperpolarization-Activated Current (I h) in Vestibular Calyx Terminals: Characterization and Role in Shaping Postsynaptic Events

Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na⁺ currents, voltage-dependent outward K⁺ currents and a K(Ca) current. Here, we characterize an inwardly rectifying conductance in gerbil semicircular canal calyx terminals (postnatal days 3–45), sensitive to voltage and to cyclic nucleotides. Using whole-cell patch clamp, we recorded from isolated calyx terminals still attached to their type I hair cells. A slowly activating, noninactivating current (I_h) was seen with hyperpolarizing voltage steps negative to the resting potential. External Cs⁺ (1–5 mM) and ZD7288 (100 μM) blocked the inward current by 97 and 83 %, respectively, confirming that I_h was carried by hyperpolarization-activated, cyclic nucleotide gated channels. Mean half-activation voltage of I_h was −123 mV, which shifted to −114 mV in the presence of cAMP. Activation of I_h was well described with a third order exponential fit to the current (mean time constant of activation, τ, was 190 ms at −139 mV). Activation speeded up significantly (τ = 136 and 127 ms, respectively) when intracellular cAMP and cGMP were present, suggesting that in vivo I_h could be subject to efferent modulation via cyclic nucleotide-dependent mechanisms. In current clamp, hyperpolarizing current steps produced a time-dependent depolarizing sag followed by either a rebound afterdepolarization or an action potential. Spontaneous excitatory postsynaptic potentials (EPSPs) became larger and wider when I_h was blocked with ZD7288. In a three-dimensional mathematical model of the calyx terminal based on Hodgkin–Huxley type ionic conductances, removal of I_h similarly increased the EPSP, whereas cAMP slightly decreased simulated EPSP size and width.     

Auditory Cortex Signs of Age-Related Hearing Loss

Age-related hearing loss, or presbyacusis, is a major public health problem that causes communication difficulties and is associated with diminished quality of life. Limited satisfaction with hearing aids, particularly in noisy listening conditions, suggests that central nervous system declines occur with presbyacusis and may limit the efficacy of interventions focused solely on improving audibility. This study of 49 older adults (M = 69.58, SD = 8.22 years; 29 female) was designed to examine the extent to which low and/or high frequency hearing loss was related to auditory cortex morphology. Low and high frequency hearing constructs were obtained from a factor analysis of audiograms from these older adults and 1,704 audiograms from an independent sample of older adults. Significant region of interest and voxel-wise gray matter volume associations were observed for the high frequency hearing construct. These effects occurred most robustly in a primary auditory cortex region (Te1.0) where there was also elevated cerebrospinal fluid with high frequency hearing loss, suggesting that auditory cortex atrophies with high frequency hearing loss. These results indicate that Te1.0 is particularly affected by high frequency hearing loss and may be a target for evaluating the efficacy of interventions for hearing loss.     

On the High Frequency Transfer of Mechanical Stimuli from the Surface of the Head to the Macular Neuroepithelium of the Mouse

Vestibular macular sensors are activated by a shearing motion between the otoconial membrane and underlying receptor epithelium. Shearing motion and sensory activation in response to an externally induced head motion do not occur instantaneously. The mechanically reactive elastic and inertial properties of the intervening tissue introduce temporal constraints on the transfer of the stimulus to sensors. Treating the otoconial sensory apparatus as an overdamped second-order mechanical system, we measured the governing long time constant (Τ_L) for stimulus transfer from the head surface to epithelium. This provided the basis to estimate the corresponding upper cutoff for the frequency response curve for mouse otoconial organs. A velocity step excitation was used as the forcing function. Hypothetically, the onset of the mechanical response to a step excitation follows an exponential rise having the form Vel_shear = U(1-e^−t/TL), where U is the applied shearing velocity step amplitude. The response time of the otoconial apparatus was estimated based on the activation threshold of macular neural responses to step stimuli having durations between 0.1 and 2.0 ms. Twenty adult C57BL/6 J mice were evaluated. Animals were anesthetized. The head was secured to a shaker platform using a non-invasive head clip or implanted skull screws. The shaker was driven to produce a theoretical forcing step velocity excitation at the otoconial organ. Vestibular sensory evoked potentials (VsEPs) were recorded to measure the threshold for macular neural activation. The duration of the applied step motion was reduced systematically from 2 to 0.1 ms and response threshold determined for each duration (nine durations). Hypothetically, the threshold of activation will increase according to the decrease in velocity transfer occurring at shorter step durations. The relationship between neural threshold and stimulus step duration was characterized. Activation threshold increased exponentially as velocity step duration decreased below 1.0 ms. The time constants associated with the exponential curve were Τ_L = 0.50 ms for the head clip coupling and T_L = 0.79 ms for skull screw preparation. These corresponded to upper −3 dB frequency cutoff points of approximately 318 and 201 Hz, respectively. T_L ranged from 224 to 379 across individual animals using the head clip coupling. The findings were consistent with a second-order mass-spring mechanical system. Threshold data were also fitted to underdamped models post hoc. The underdamped fits suggested natural resonance frequencies on the order of 278 to 448 Hz as well as the idea that macular systems in mammals are less damped than generally acknowledged. Although estimated indirectly, it is argued that these time constants reflect largely if not entirely the mechanics of transfer to the sensory apparatus. The estimated governing time constant of 0.50 ms for composite data predicts high frequency cutoffs of at least 318 Hz for the intact otoconial apparatus of the mouse.     

Experimental Measurement of Utricle System Dynamic Response to Inertial Stimulus

The membranous utricle sac of the red-eared turtle was mounted in a piezoelectric actuated platform mounted on the stage of a light microscope. The piezoelectric actuator oscillated the base of the neuroepithelium along a linear axis. Displacements were in the plane of the utricle and consisted of a linear sinusoidal-sweep signal starting at 0 and increasing to 500 Hz over 5 s. This inertial stimulus caused measurable shear displacement of the otoconial layer’s dorsal surface, resulting in shear deformation of the gelatinous and column filament layers. Displacements of the otoconial layer and a reference point on the neuroepithelium were filmed at 2,000 frames/s with a high-speed video camera during oscillations. Image registration was performed on the video to track displacements with a resolution better than 15 nm. The displacement waveforms were then matched to a linear second-order model of the dynamic system. The model match identified two system mechanical parameters—the natural circular frequency ω_n and the damping ratio ζ—that characterized the utricle dynamic response. The median values found for the medial-lateral axis on 20 utricles with 95 % confidence intervals in parenthesis were as follows: ω_n = 374 (353, 396) Hz and ζ = 0.50 (0.47, 0.53). The anterior-posterior axis values were not significantly different: ω_n = 409 (390, 430) Hz and ζ = 0.53 (0.48, 0.57). The results have two relevant and significant dynamic system findings: (1) a higher than expected natural frequency and (2) significant under damping. Previous to this study, utricular systems were treated as overdamped and with natural frequencies much lower that measured here. Both of these system performance findings result in excellent utricle time response to acceleration stimuli and a broad frequency bandwidth up to 100 Hz. This study is the first to establish the upper end of this mechanical system frequency response of the utricle in any animal.     

Three-Dimensional Vibration-Induced Vestibulo-ocular Reflex Identifies Vertical Semicircular Canal Dehiscence

Vertical semicircular canal dehiscence (VSCD) due to superior canal dehiscence (SCD) or posterior canal dehiscence (PCD) of the temporal bone causes vestibular and cochlear hypersensitivity to sound. This study aimed to characterize the vibration-induced vestibulo-ocular reflex (ViVOR) in VSCD. ViVORs in one PCD and 17 SCD patients, confirmed by CT imaging reformatted in semicircular canal planes, were measured with dual-search coils as binocular three-dimensional eye rotations induced by skull vibrations from a bone oscillator (B71—10 ohms) at 7 ms, 500 Hz, 135-dB peak-force level (re: 1 μN). The ViVOR eye rotation axes were computed by vector analysis and referenced to known semicircular canal planes. Onset latency of the ViVOR was 11 ms. ViVOR from VSCD was up to nine times greater than normal. The ViVOR’s torsional rotation was always contraversive-torsional (the eye’s upper pole rotated away from the stimulated ear), i.e. its direction was clockwise from a left and counterclockwise from a right VSCD, thereby lateralizing the side of the VSCD. The ViVORs vertical component distinguishes PCD from SCD, being downwards in PCD and upwards in SCD. In unilateral VSCD, the ViVOR eye rotation axis aligned closest to the dehiscent vertical semicircular canal axis from either ipsilateral or contralateral mastoid vibrations. However, in bilateral VSCDs, the ViVOR eye rotation axis lateralized to the ipsilateral dehiscent vertical semicircular canal axis. ViVOR was evoked in ossicular chain dysfunction, even when air-conducted click vestibulo-ocular reflex (VOR) was absent or markedly reduced. Hence, ViVOR could be a useful measurement to identify unilateral or bilateral VSCD even in the presence of ossicular chain dysfunction.     

Einseitige auditorische Neuropathie

Auditory neuropathy presents with normal otoacoustic emissions combined with pathological findings in brainstem evoked response audiometry. Normally, the auditory neuropathy is bilateral. We report about a 9 year old child where we could diagnose a unilateral deafness in spite of regular TEOAE and DPOAE. No reproducible biosignals were seen when the right ear was stimulated with alternating click stimuli at a level of 80 dB. On the left side, the latency of the potentials was normal. A cranial MRI showed normal anatomy. In order to determine a unilateral deafness, objective tests (e.g., OAE, BERA) and subjective tests should be used.     

Examining the Electro-Neural Interface of Cochlear Implant Users Using Psychophysics,CT Scans,and Speech Understanding

This study examines the relationship between focused-stimulation thresholds, electrode positions, and speech understanding in deaf subjects treated with a cochlear implant (CI). Focused stimulation is more selective than monopolar stimulation, which excites broad regions of the cochlea, so may be more sensitive as a probe of neural survival patterns. Focused thresholds are on average higher and more variable across electrodes than monopolar thresholds. We presume that relatively high focused thresholds are the result of larger distances between the electrodes and the neurons. Two factors are likely to contribute to this distance: (1) the physical position of electrodes relative to the modiolus, where the excitable auditory neurons are normally located, and (2) the pattern of neural survival along the length of the cochlea, since local holes in the neural population will increase the distance between an electrode and the nearest neurons. Electrode-to-modiolus distance was measured from high-resolution CT scans of the cochleae of CI users whose focused-stimulation thresholds were also measured. A hierarchical set of linear models of electrode-to-modiolus distance versus threshold showed a significant increase in threshold with electrode-to-modiolus distance (average slope = 11 dB/mm). The residual of these models was hypothesized to reflect neural survival in each subject. Consonant–Nucleus–Consonant (CNC) word scores were significantly correlated with the within-subject variance of threshold (r² = 0.82), but not with within-subject variance of electrode distance (r² = 0.03). Speech understanding also significantly correlated with how well distance explained each subject’s threshold data (r² = 0.63). That is, subjects with focused thresholds that were well described by electrode position had better speech scores. Our results suggest that speech understanding is highly impacted by individual patterns of neural survival and that these patterns manifest themselves in how well (or poorly) electrode position predicts focused thresholds.     

Dynamic Displacement of Normal and Detached Semicircular Canal Cupula

The dynamic displacement of the semicircular canal cupula and modulation of afferent nerve discharge were measured simultaneously in response to physiological stimuli in vivo. The adaptation time constant(s) of normal cupulae in response to step stimuli averaged 36 s, corresponding to a mechanical lower corner frequency for sinusoidal stimuli of 0.0044 Hz. For stimuli equivalent to 40–200 deg/s of angular head velocity, the displacement gain of the central region of the cupula averaged 53 nm per deg/s. Afferents adapted more rapidly than the cupula, demonstrating the presence of a relaxation process that contributes significantly to the neural representation of angular head motions by the discharge patterns of canal afferent neurons. We also investigated changes in time constants of the cupula and afferents following detachment of the cupula at its apex—mechanical detachment that occurs in response to excessive transcupular endolymph pressure. Detached cupulae exhibited sharply reduced adaptation time constants (300 ms–3 s, n = 3) and can be explained by endolymph flowing rapidly over the apex of the cupula. Partially detached cupulae reattached and normal afferent discharge patterns were recovered 5–7 h following detachment. This regeneration process may have relevance to the recovery of semicircular canal function following head trauma.     

Effect of colouring green stage zirconia on the adhesion of veneering ceramics with different thermal expansion coefficients

This study evaluated the adhesion of zirconia core ceramics with their corresponding veneering ceramics, having different thermal expansion coefficients （TECs）, when zirconia ceramics were coloured at green stage. Zirconia blocks （N=240; 6 mm x 7 mm x 7 mm） were manufactured from two materials namely, ICE Zirconia （Group 1） and Prettau Zirconia （Group 2）. In their green stage, they were randomly divided into two groups. Half of the specimens were coloured with colouring liquid （shade A2）, Three different veneering ceramics with different TEC （ICE Ceramic, GC Initial Zr and IPS e.max Ceram） were fired on both coloured and non-coloured zirconia cores. Specimens of high noble alloys （Esteticor Plus） veneered with ceramic （VM 13） （n= 16） acted as the control group. Core-veneer interface of the specimens were subjected to shear force in the Universal Testing Machine （0.5 mm-min-1）. Neither the zirconia core material （P=0.318） nor colouring （P=0.188） significantly affected the results （three-way analysis of variance, Tukey＇s test）. But the results were significantly affected by the veneering ceramic （P=0.000）. Control group exhibited significantly higher mean bond strength values （45.7__.8） MPa than all other tested groups （（27.1__.4.1）-（39.7__.4.7） and （27.4__.5.6）-（35.9___4.7） MPa with and without colouring, respectively） （P~0.001）. While in zirconia-veneer test groups, predominantly mixed type of failures were observed with the veneering ceramic covering ~ 1/3 of the substrate surface, in the metal-ceramic group, veneering ceramic was left adhered 1/3 of the metal surface. Colouring zirconia did not impair adhesion of veneering ceramic, but veneering ceramic had a significant influence on the core-veneer adhesion. Metal-ceramic adhesion was more reliable than all zirconia-veneer ceramics tested.     

Characterization of the Sheep Round Window Membrane

Intratympanic injection is a clinically used approach to locally deliver therapeutic molecules to the inner ear. Drug diffusion, at least in part, is presumed to occur through the round window membrane (RWM), one of the two openings to the inner ear. Previous studies in human temporal bones have identified a three-layered structure of the RWM with a thickness of 70–100 μm. This is considerably thicker than the RWM in rodents, which are mostly used to model RWM permeability and assess drug uptake. The sheep has been suggested as a large animal model for inner ear research given the similarities in structure and frequency range for hearing. Here, we report the structure of the sheep RWM. The RWM is anchored within the round window niche (average vertical diameter of 2.1 ± 0.3 mm and horizontal diameter of 2.3 ± 0.4 mm) and has a curvature that leans towards the scala tympani. The centre of the RWM is the thinnest (55–71 μm), with increasing thickness towards the edges (< 171 μm), where the RWM forms tight attachments to the surrounding bony niche. The layered RWM structure, including an outer epithelial layer, middle connective tissue and inner epithelial layer, was identified with cellular features such as wavy fibre bundles, melanocytes and blood vessels. An attached “meshwork structure” which extends over the cochlear aqueduct was seen, as in humans. The striking anatomical similarities between sheep and human RWM suggest that sheep may be evaluated as a more appropriate system to predict RWM permeability and drug delivery in humans than rodent models.     

Evolutionary Paths to Mammalian Cochleae

Evolution of the cochlea and high-frequency hearing (>20 kHz; ultrasonic to humans) in mammals has been a subject of research for many years. Recent advances in paleontological techniques, especially the use of micro-CT scans, now provide important new insights that are here reviewed. True mammals arose more than 200 million years (Ma) ago. Of these, three lineages survived into recent geological times. These animals uniquely developed three middle ear ossicles, but these ossicles were not initially freely suspended as in modern mammals. The earliest mammalian cochleae were only about 2 mm long and contained a lagena macula. In the multituberculate and monotreme mammalian lineages, the cochlea remained relatively short and did not coil, even in modern representatives. In the lineage leading to modern therians (placental and marsupial mammals), cochlear coiling did develop, but only after a period of at least 60 Ma. Even Late Jurassic mammals show only a 270 ° cochlear coil and a cochlear canal length of merely 3 mm. Comparisons of modern organisms, mammalian ancestors, and the state of the middle ear strongly suggest that high-frequency hearing (>20 kHz) was not realized until the early Cretaceous (~125 Ma). At that time, therian mammals arose and possessed a fully coiled cochlea. The evolution of modern features of the middle ear and cochlea in the many later lineages of therians was, however, a mosaic and different features arose at different times. In parallel with cochlear structural evolution, prestins in therian mammals evolved into effective components of a new motor system. Ultrasonic hearing developed quite late—the earliest bat cochleae (~60 Ma) did not show features characteristic of those of modern bats that are sensitive to high ultrasonic frequencies.     

Brainstem auditory evoked potentials after irradiation of nasopharyngeal carcinoma--report on two cases with myelopathy of the brainstem

Brainstem auditory evoked potentials (BAEP) were recorded in two patients with nasopharyngeal carcinoma (NPC) irradiated 14 and three years ago respectively and compared with 15 healthy controls. The patients had features of post-irradiation myelopathy of the brainstem with reduced gag reflex, unilateral vocal cord paralysis and fasciculation of the tongue. The first patient had a blind left eye. The second patient had quadriparesis. All ears revealed post-irradiation otitis media changes and mixed deafness. BAEP was not recognizable in the left ear of the first patient and was normal in the left ear of the second patient. Simultaneous electrocochleogram and BAEP were recorded from the right ear of the first case. The wave I-V latency interval were prolonged in both right ears. In the absence of local recurrence and brain secondaries, these BAEP changes are attributed to the post-irradiation myelopathy of brainstem.