Saccular otoconia as a cause of Ménière's disease: hypothesis based on two theories.

BACKGROUND: The cause of Ménière's disease remains enigmatic after 156 years. Schuknecht's rupture and potassium intoxication theory of attacks was based on histological studies. OBJECTIVES: This paper aimed to: present the most contemporary evidence indicating that ruptures do not usually occur, and discuss the possibility that detached saccular otoconia are the main cause of Ménière's disease; and to establish an unequivocal definition of the age of Ménière's disease onset. METHOD: The paper reviews the electrophysiological basis of the Gibson-Arenberg drainage theory used to explain vertigo attacks. The current, limited knowledge of the likely fate of detached saccular otoconia is discussed. RESULTS: Electrophysiological studies during attacks do not support endolymph ruptures, but rather endolymph flowing in one direction and then in the opposite direction. Age of onset for Ménière's disease parallels that for benign paroxysmal positional vertigo. CONCLUSION: The similarity of age of onset spectrum for Ménière's disease and benign paroxysmal positional vertigo raises the possibility that the two conditions have the same fundamental cause.

Morphology of the utricular otolith organ in the toadfish, Opsanus tau.

The utricle provides the vestibular reflex pathways with the sensory codes of inertial acceleration of self-motion and head orientation with respect to gravity to control balance and equilibrium. Here we present an anatomical description of this structure in the adult oyster toadfish and establish a morphological basis for interpretation of subsequent functional studies. Light, scanning, and transmission electron microscopy techniques were applied to visualize the sensory epithelium at varying levels of detail, its neural innervation and its synaptic organization. Scanning electron microscopy was used to visualize otolith mass and morphological polarization patterns of hair cells. Afferent nerve fibers were visualized following labeling with biocytin, and light microscope images were used to make three-dimensional (3-D) reconstructions of individual labeled afferents to identify dendritic morphology with respect to epithelial location. Transmission electron micrographs were compiled to create a serial 3-D reconstruction of a labeled afferent over a segment of its dendritic field and to examine the cell-afferent synaptic contacts. Major observations are: a well-defined striola, medial and lateral extra-striolar regions with a zonal organization of hair bundles; prominent lacinia projecting laterally; dependence of hair cell density on macular location; narrow afferent dendritic fields that follow the hair bundle polarization; synaptic specializations issued by afferents are typically directed towards a limited number of 7-13 hair cells, but larger dendritic fields in the medial extra-striola can be associated with > 20 hair cells also; and hair cell synaptic bodies can be confined to only an individual afferent or can synapse upon several afferents.

Examination of Utricular Response Using oVEMP and Unilateral Centrifugation Rotation Testing.

OBJECTIVES: Significant advancements have been made toward the clinical assessment of utricular function through ocular vestibular-evoked myogenic potentials (oVEMP) and unilateral centrifugation (UCF) testing. To date, no study has examined intrasubject relationships between these measures. The study hypothesis was that intrasubject responses from oVEMP and UCF testing would be correlated inasmuch as both tests have been reported to assess utricular function. DESIGN: UCF rotations and oVEMP testing were performed on healthy volunteers, aged 18 to 62 years. A within-subject study design compared and correlated UCF outcome measures of ocular counterroll, subjective visual vertical, and ocular counterroll-gravitational inertial acceleration slope against peak to peak oVEMP N1-P1 amplitude. RESULTS: Correlational analyses failed to reveal any significant relationships between oVEMP amplitude and UCF responses suggesting that these tests may be inciting different response properties within the utricular system. CONCLUSIONS: Various anatomical and physiological differences within the utricle, in addition to the fundamental differences in stimulus properties between the oVEMP and UCF tests, could explain the lack of significant correlations between these measures and suggest that oVEMP and UCF testing may be complimentary in their evaluation of the utricular system. These data reinforce the complexities of the utricular system and provide further insight into the difficulties encountered in its clinical assessment.

An operating principle of the turtle utricle to detect wide dynamic range.

The utricle encodes both static information such as head orientation, and dynamic information such as vibrations. It is not well understood how the utricle can encode both static and dynamic information for a wide dynamic range (from <0.05 to >2 times the gravitational acceleration; from DC to > 1000 Hz vibrations). Using computational models of the hair cells in the turtle utricle, this study presents an explanation on how the turtle utricle encodes stimulations over such a wide dynamic range. Two hair bundles were modeled using the finite element method-one representing the striolar hair cell (Cell S), and the other representing the medial extrastriolar hair cell (Cell E). A mechano-transduction (MET) channel model was incorporated to compute MET current (iMET) due to hair bundle deflection. A macro-mechanical model of the utricle was used to compute otoconial motions from head accelerations (aHead). According to known anatomical data, Cell E has a long kinocilium that is embedded into the stiff otoconial layer. Unlike Cell E, the hair bundle of Cell S falls short of the otoconial layer. Considering such difference in the mechanical connectivity between the hair cell bundle and the otoconial layer, three cases were simulated: Cell E displacement-clamped, Cell S viscously-coupled, and Cell S displacement-clamped. Head accelerations at different amplitude levels and different frequencies were simulated for the three cases. When a realistic head motion was simulated, Cell E was responsive to head orientation, while the viscously-coupled Cell S was responsive to fast head motion imitating the feeding strike of a turtle.

Saccular measurements in routine MRI can predict hydrops in Menière's disease.

Most patients with suspicion of hydrops do not have access to MRI with 3D reconstruction of the endolymphatic space. Our main objective was to show that measurements of the saccule on a non-enhanced 3D-T2 MRI could show hydrops and help diagnose Menière disease. We conducted a prospective study from 2015 to 2016 to compare consecutive patients consulting for Menière's disease to a control group (patients with unilateral non-hydrops disorders and contralateral healthy ears). They all received full auditory and vestibular testing. They also underwent a 3-Tesla 3D-T2 MRI using CISS sequence (0.4 mm thick slices), which were blindly evaluated by two independent neuroradiologists. The saccular height and width were measured in a coronal plane and Menière's disease patients' symptomatic ears were compared to asymptomatic and control ears. 36 patients with definite Menière's disease and 36 control patients were studied, including 42 symptomatic Menière, 30 asymptomatic Menière and 72 control ears. Saccular measurements were significantly different between symptomatic Menière ears compared to healthy ears (1.59 vs 1.32 mm, p < 0.001 for height; 1.13 vs 0.90 mm, p < 0.001 for width). Symptomatic and asymptomatic Menière ears' measurements were not significantly different (p = 0.307 and p = 0.109). Using ROC curve, we found cut-off values for saccular height 1.51 mm, Se = 63%, Sp = 95% and width 1.05 mm, Se = 41%, Sp = 95%. Routine 3D-T2 MRI, which patients must undergo for differential diagnosis, could help diagnose hydrops with high specificity using saccular measurements.

Potenciales evocados vestibulares miogénicos / Myogenic vestibular evoked potentials

El equilibrio es el estado de un cuerpo requerido por fuerzas opuestas e iguales, es el mantenimiento de la posición corporal adecuada a cada circunstancia, tanto en condición estática como dinámica. Los laberintos posteriores regulan en gran proporción esas fuerzas y la normalidad está basada en la igualdad de sus tonos, están conformados por el vestíbulo membranoso (constituido por el utrículo y el sáculo) y los conductos semicirculares. Los conductos semicirculares pueden ser examinados a través de las pruebas vestibulares rotatorias o bicalóricas, los órganos otolíticos (utrículo y sáculo) por su ubicación anatómica quedan limitados en el estudio de sus funciones; sin embargo, existe una prueba neurofisiológica (potencial evocado vestibular miogénico) capaz de explorar la función del sáculo y del nervio vestibular inferior, que aprovecha la posibilidad que tiene el sáculo de ser estimulado con altas intensidad de sonido en diferentes frecuencias(AU)

Equilibrium is the required state of a body by opposing and equal forces, it is the maintenance of the body position appropriate to each circumstance, both in static and dynamic condition. The posterior labyrinths regulate these forces to a great extent, and normality is based on the equality of their tones. They are made up of the semicircular ducts and the membranous vestibule (constituted by the utricle and the saccule). Semicircular ducts can be examined through rotational or bicalorical vestibular tests, otolithic organs (utricle and saccule) because of their anatomical location are limited in the study of their functions, however, there is a neurophysiological test (evoked vestibular myogenic potential) capable of exploring the function of the saccule and inferior vestibular nerve, which takes advantage of the ability of the saccule to be stimulated with high sound intensity at different frequencies(AU)

Symmetries of a generic utricular projection: neural connectivity and the distribution of utricular information.

Sensory contribution to perception and action depends on both sensory receptors and the organization of pathways (or projections) reaching the central nervous system. Unlike the semicircular canals that are divided into three discrete sensitivity directions, the utricle has a relatively complicated anatomical structure, including sensitivity directions over essentially 360° of a curved, two-dimensional disk. The utricle is not flat, and we do not assume it to be. Directional sensitivity of individual utricular afferents decreases in a cosine-like fashion from peak excitation for movement in one direction to a null or near null response for a movement in an orthogonal direction. Directional sensitivity varies slowly between neighboring cells except within the striolar region that separates the medial from the lateral zone, where the directional selectivity abruptly reverses along the reversal line. Utricular primary afferent pathways reach the vestibular nuclei and cerebellum and, in many cases, converge on target cells with semicircular canal primary afferents and afference from other sources. Mathematically, some canal pathways are known to be characterized by symmetry groups related to physical space. These groups structure rotational information and movement. They divide the target neural center into distinct populations according to the innervation patterns they receive. Like canal pathways, utricular pathways combine symmetries from the utricle with those from target neural centers. This study presents a generic set of transformations drawn from the known structure of the utricle and therefore likely to be found in utricular pathways, but not exhaustive of utricular pathway symmetries. This generic set of transformations forms a 32-element group that is a semi-direct product of two simple abelian groups. Subgroups of the group include order-four elements corresponding to discrete rotations. Evaluation of subgroups allows us to functionally identify the spatial implications of otolith and canal symmetries regarding action and perception. Our results are discussed in relation to observed utricular pathways, including those convergent with canal pathways. Oculomotor and other sensorimotor systems are organized according to canal planes. However, the utricle is evolutionarily prior to the canals and may provide a more fundamental spatial framework for canal pathways as well as for movement. The fullest purely otolithic pathway is likely that which reaches the lumbar spine via Deiters' cells in the lateral vestibular nucleus. It will be of great interest to see whether symmetries predicted from the utricle are identified within this pathway.

What the Toadfish Ear Tells the Toadfish Brain About Sound.

Of the three, paired otolithic endorgans in the ear of teleost fishes, the saccule is the one most often demonstrated to have a major role in encoding frequencies of biologically relevant sounds. The toadfish saccule also encodes sound level and sound source direction in the phase-locked activity conveyed via auditory afferents to nuclei of the ipsilateral octaval column in the medulla. Although paired auditory receptors are present in teleost fishes, binaural processes were believed to be unimportant due to the speed of sound in water and the acoustic transparency of the tissues in water. In contrast, there are behavioral and anatomical data that support binaural processing in fishes. Studies in the toadfish combined anatomical tract-tracing and physiological recordings from identified sites along the ascending auditory pathway to document response characteristics at each level. Binaural computations in the medulla and midbrain sharpen the directional information provided by the saccule. Furthermore, physiological studies in the central nervous system indicated that encoding frequency, sound level, temporal pattern, and sound source direction are important components of what the toadfish ear tells the toadfish brain about sound.

Comparison of Electrophysiological Auditory Measures in Fishes.

Sounds provide fishes with important information used to mediate behaviors such as predator avoidance, prey detection, and social communication. How we measure auditory capabilities in fishes, therefore, has crucial implications for interpreting how individual species use acoustic information in their natural habitat. Recent analyses have highlighted differences between behavioral and electrophysiologically determined hearing thresholds, but less is known about how physiological measures at different auditory processing levels compare within a single species. Here we provide one of the first comparisons of auditory threshold curves determined by different recording methods in a single fish species, the soniferous Hawaiian sergeant fish Abudefduf abdominalis, and review past studies on representative fish species with tuning curves determined by different methods. The Hawaiian sergeant is a colonial benthic-spawning damselfish (Pomacentridae) that produces low-frequency, low-intensity sounds associated with reproductive and agonistic behaviors. We compared saccular potentials, auditory evoked potentials (AEP), and single neuron recordings from acoustic nuclei of the hindbrain and midbrain torus semicircularis. We found that hearing thresholds were lowest at low frequencies (~75-300 Hz) for all methods, which matches the spectral components of sounds produced by this species. However, thresholds at best frequency determined via single cell recordings were ~15-25 dB lower than those measured by AEP and saccular potential techniques. While none of these physiological techniques gives us a true measure of the auditory "perceptual" abilities of a naturally behaving fish, this study highlights that different methodologies can reveal similar detectable range of frequencies for a given species, but absolute hearing sensitivity may vary considerably.

Diversity of Inner Ears in Fishes: Possible Contribution Towards Hearing Improvements and Evolutionary Considerations.

Fishes have evolved the largest diversity of inner ears among vertebrates. While G. Retzius introduced us to the diversity of the gross morphology of fish ears in the late nineteenth century, it was A. N. Popper who unraveled the large variety of the fine structure during the last four decades. Modifications of the basic inner ear structure-consisting of three semicircular canals and their sensory epithelia, the cristae and three otolithic end organs (utricle, saccule, lagena) including the maculae-mainly relate to the saccule and lagena and the respective sensory epithelia, the macula sacculi and macula lagenae. Despite the profound morphological knowledge of inner ears and the morphological variability, the functional significance of this diversity is still largely unknown. The aims of this review are therefore twofold. First it provides an update of the state of the art of inner ear diversity in bony fishes. Second it summarizes and discusses hypotheses on the evolution of this diversity as well as formulates open questions and promising approaches to tackle these issues.

SoxC transcription factors are essential for the development of the inner ear.

Hair cells, the mechanosensory receptors of the inner ear, underlie the senses of hearing and balance. Adult mammals cannot adequately replenish lost hair cells, whose loss often results in deafness or balance disorders. To determine the molecular basis of this deficiency, we investigated the development of a murine vestibular organ, the utricle. Here we show that two members of the SoxC family of transcription factors, Sox4 and Sox11, are down-regulated after the epoch of hair cell development. Conditional ablation of SoxC genes in vivo results in stunted sensory organs of the inner ear and loss of hair cells. Enhanced expression of SoxC genes in vitro conversely restores supporting cell proliferation and the production of new hair cells in adult sensory epithelia. These results imply that SoxC genes govern hair cell production and thus advance these genes as targets for the restoration of hearing and balance.

Turtle utricle dynamic behavior using a combined anatomically accurate model and experimentally measured hair bundle stiffness.

Anatomically correct turtle utricle geometry was incorporated into two finite element models. The geometrically accurate model included appropriately shaped macular surface and otoconial layer, compact gel and column filament (or shear) layer thicknesses and thickness distributions. The first model included a shear layer where the effects of hair bundle stiffness was included as part of the shear layer modulus. This solid model's undamped natural frequency was matched to an experimentally measured value. This frequency match established a realistic value of the effective shear layer Young's modulus of 16 Pa. We feel this is the most accurate prediction of this shear layer modulus and fits with other estimates (Kondrachuk, 2001b). The second model incorporated only beam elements in the shear layer to represent hair cell bundle stiffness. The beam element stiffness's were further distributed to represent their location on the neuroepithelial surface. Experimentally measured striola hair cell bundles mean stiffness values were used in the striolar region and the mean extrastriola hair cell bundles stiffness values were used in this region. The results from this second model indicated that hair cell bundle stiffness contributes approximately 40% to the overall stiffness of the shear layer-hair cell bundle complex. This analysis shows that high mass saccules, in general, achieve high gain at the sacrifice of frequency bandwidth. We propose the mechanism by which this can be achieved is through increase the otoconial layer mass. The theoretical difference in gain (deflection per acceleration) is shown for saccules with large otoconial layer mass relative to saccules and utricles with small otoconial layer mass. Also discussed is the necessity of these high mass saccules to increase their overall system shear layer stiffness. Undamped natural frequencies and mode shapes for these sensors are shown.

A unique swim bladder-inner ear connection in a teleost fish revealed by a combined high-resolution microtomographic and three-dimensional histological study.

BACKGROUND: In most modern bony fishes (teleosts) hearing improvement is often correlated with a close morphological relationship between the swim bladder or other gas-filled cavities and the saccule or more rarely with the utricle. A connection of an accessory hearing structure to the third end organ, the lagena, has not yet been reported. A recent study in the Asian cichlid Etroplus maculatus provided the first evidence that a swim bladder may come close to the lagena. Our study was designed to uncover the swim bladder-inner ear relationship in this species. We used a new approach by applying a combination of two high-resolution techniques, namely microtomographic (microCT) imaging and histological serial semithin sectioning, providing the basis for subsequent three-dimensional reconstructions. Prior to the morphological study, we additionally measured auditory evoked potentials at four frequencies (0.5, 1, 2, 3 kHz) to test the hearing abilities of the fish. RESULTS: E. maculatus revealed a complex swim bladder-inner ear connection in which a bipartite swim bladder extension contacts the upper as well as the lower parts of each inner ear, a condition not observed in any other teleost species studied so far. The gas-filled part of the extension is connected to the lagena via a thin bony lamella and is firmly attached to this bony lamella with connective material. The second part of the extension, a pad-like structure, approaches the posterior and horizontal semicircular canals and a recessus located posterior to the utricle. CONCLUSIONS: Our study is the first detailed report of a link between the swim bladder and the lagena in a teleost species. We suggest that the lagena has an auditory function in this species because the most intimate contact exists between the swim bladder and this end organ. The specialized attachment of the saccule to the cranial bone and the close proximity of the swim bladder extension to the recessus located posterior to the utricle indicate that the saccule and the utricle also receive parallel inputs from the swim bladder extension. We further showed that a combination of non-destructive microCT imaging with histological analyses on the same specimen provides a powerful tool to decipher and interpret fine structures and to compensate for methodological artifacts.

Vortical flow in the utricle and the ampulla: a computational study on the fluid dynamics of the vestibular system.

We present a computational study of the fluid dynamics in healthy semicircular canals (SCCs) and the utricle. The SCCs are the primary sensors for angular velocity and are located in the vestibular part of the inner ear. The SCCs are connected to the utricle that hosts the utricular macula, a sensor for linear acceleration. The transduction of angular motion is triggered by the motion of a fluid called endolymph and by the interaction of this fluid with the sensory structures of the SCC. In our computations, we observe a vortical flow in the utricle and in the ampulla (the enlarged terminal part of the SCCs) which can lead to flow velocities in the utricle that are even higher than those in the SCCs. This is a fundamentally new result which is in contrast to the common belief that the fluid velocities in the utricle are negligible from a physiological point of view. Moreover, we show that the wall shear stresses in the utricle and the ampulla are maximized at the positions of the sensory epithelia. Possible physiological and clinical implications are discussed.

Condition-dependent auditory processing in the round goby (Neogobius melanostomus): links to sex, reproductive condition and female estrogen levels.

Neural responses to sensory stimuli often differ between sexes, vary seasonally, and can be regulated by endocrine activity, but the ecological and physiological mechanisms driving such patterns are not well understood. The current study examined how auditory function in the round goby (Neogobius melanostomus), a vocal teleost, co-varied with sex, reproductive condition and female plasma 17ß-estradiol level. Auditory evoked potentials were collected in response to tone pips (100-600 Hz) and a natural round goby pulse vocalization. Additionally, saccule hair cell densities were compared across reproductive groups. Auditory threshold was evaluated in terms of pressure and particle acceleration, and response amplitude and onset latency were measured at 10 dB above threshold. Relative to males, females displayed lower auditory thresholds in response to the natural vocalization and to tones at 300-600 Hz, and had a higher density of saccule hair cells. The 17ß-estradiol level was positively associated with amplitude and latency for the pulse stimulus and with both threshold and amplitude for tones at 100-200 Hz in females. Relative to non-reproductive males, reproductive males exhibited longer response latencies at 100-200 Hz. The results demonstrate sexual dimorphism in auditory function in a teleost fish as well as intra-sexual variation, partially based on hormone levels. The current research further identifies links between auditory function and reproductive behaviors in fishes and provides a finer-scaled analysis of how this behavior is reflected at the level of the sensory systems facilitating signal reception.

A re-investigation of the role of utricular asymmetries in Space Motion Sickness.

During the first days of spaceflight, about 50-70% of the astronauts experience symptoms of Space Motion Sickness (SMS). It has been proposed that an asymmetry between the left and right otolith organs contributes to an astronaut's individual susceptibility. A recently developed test to measure unilateral utricular function enabled us to re-investigate this so-called otolith asymmetry hypothesis, while using the paradigm of sustained centrifugation as a ground based model for SMS. This latter paradigm has been shown to elicit symptoms similar to those of SMS and is referred to as Sickness Induced by Centrifugation (SIC). In 15 healthy subjects unilateral utricular function was assessed by recording ocular counter rolling during a unilateral centrifugation paradigm. In addition, saccular function was assessed by recording Vestibular Evoked Myogenic Potentials (VEMPs), and horizontal semicircular canal function was assessed using bithermal caloric stimulation. SIC-susceptible subjects showed a marginally higher degree of utricular asymmetry, utricular sensitivity and semicircular canal sensitivity (p < 0.1) than the non-susceptible group. Interestingly, a logistic regression model using both utricular and semicircular canal parameters led to a correct classification of 91% of the subjects. As such, these results suggest that otolith asymmetry is at most one factor - and not present in all susceptible subjects - in defining susceptibility to SMS and SIC. Both the utricular and the canal system might be involved as well.

The ears of butterflyfishes (Chaetodontidae): 'hearing generalists' on noisy coral reefs?

Analysis of the morphology of all three otolithic organs (sacculus, lagena and utriculus), including macula shape, hair cell morphology, density, orientation pattern, otolith morphology and the spatial relationships of the swimbladder and ear, reveals that butterflyfishes in the genera Chaetodon (which has anterior swimbladder horns) and Forcipiger (which lacks anterior swimbladder horns) both demonstrate the ear morphology typical of teleosts that lack otophysic connections, fishes that have traditionally been considered to be 'hearing generalists'.

A critical review of the neurophysiological evidence underlying clinical vestibular testing using sound, vibration and galvanic stimuli.

In addition to activating cochlear receptors, air conducted sound (ACS) and bone conducted vibration (BCV) activate vestibular otolithic receptors, as shown by neurophysiological evidence from animal studies--evidence which is the foundation for using ACS and BCV for clinical vestibular testing by means of vestibular-evoked myogenic potentials (VEMPs). Recent research is elaborating the specificity of ACS and BCV on vestibular receptors. The evidence that saccular afferents can be activated by ACS has been mistakenly interpreted as showing that ACS only activates saccular afferents. That is not correct - ACS activates both saccular and utricular afferents, just as BCV activates both saccular and utricular afferents, although the patterns of activation for ACS and BCV do not appear to be identical. The otolithic input to sternocleidomastoid muscle appears to originate predominantly from the saccular macula. The otolithic input to the inferior oblique appears to originate predominantly from the utricular macula. Galvanic stimulation by surface electrodes on the mastoids very generally activates afferents from all vestibular sense organs. This review summarizes the physiological results, the potential artifacts and errors of logic in this area, reconciles apparent disagreements in this field. The neurophysiological results on BCV have led to a new clinical test of utricular function - the n10 of the oVEMP. The cVEMP tests saccular function while the oVEMP tests utricular function.

The configuration and attachment of the utricular and saccular maculae to the temporal bone. New evidence from microtomography-CT studies of the membranous labyrinth.

High-resolution X-ray microtomography (micro-CT) was used to show the spatial configuration of the membranous labyrinth of the fixed guinea pig and human inner ear. Whole temporal bones were en bloc stained in 2% osmium tetroxide for 2 days or more to allow the osmium to attach to the membranes of the inner ear, and then scanned with a Skyscan 1172 micro-CT with highest resolution of 8 microns. The scans were segmented and reconstructed. The findings for guinea pigs and humans are similar. The saccular macula is closely attached to the curved medial wall of the temporal bone, but in both human and guinea pig the utricular macula is attached to the temporal bone only at the anterior region of the macula, and, as others have reported previously, much of the caudal area of the utricular macula is tenuously supported by a thin membrane, just above the dorsal margin of the stapes. This tenuous support may have important consequences for the sensing of forces by the utricular macula. Combining information from a dissected human horizontal canal with CT images allows an estimate of the orientation of the horizontal canal crista in human subjects, data which are necessary for treatment of benign paroyxsmal positional vertigo of the horizontal canal. The very high resolution achieved by micro-CT shows that reconstruction from inadequately sampled CT data produces images that are not anatomically correct, so that canal deformations and aplasias may appear to be present.