Vestibular Response to Electrical Stimulation of the Otolith Organs. Implications in the Development of A Vestibular Implant for the Improvement of the Sensation of Gravitoinertial Accelerations.

OBJECTIVE: Electrical stimulation of the utricular and saccular portions of the vestibular nerve improves stability in patients suffering from vestibular dysfunction. The main objective of this study was to evaluate a new technique, vestibular response telemetry (VRT), for measuring the electrically evoked vestibular compound action potential (saccular and utricular) after stimulating the otolith organ (saccular and utricular) in adults. This study used evidence that the otolith organ can be electrically stimulated in order to develop a new vestibular implant design to improve the sensation of gravitoinertial acceleration. MATERIALS AND METHODS: Four adult patients were evaluated by using a variety of measurement procedures with novel VRT software. VRT values were obtained by stimulating with three full-band Nucleus CI24RE (ST) electrodes. Specific stimuli were used. Simultaneously, electrical ocular vestibular evoked myogenic potentials (eoVEMPs) were recorded in the contralateral side. RESULTS: Electrically evoked compound action potentials were obtained in 10 of the 12 electrodes tested, and eoVEMPs were recorded when VRT was present. In addition to the validation of this technique, a set of default clinical test parameters was established. The VRT response morphology consisted of a biphasic waveform with an initial negative peak (N1) followed by a positive peak (P1), and latencies were typically 400 µs for N1 and 800 µs for P1. The consequences for the development of a vestibular implant for the improvement of gravitoinertial acceleration sensation are also presented. CONCLUSION: The VRT measurement technique has been shown to be a useful tool to record neural response on the otolith organ, and thus it is a convenient tool to evaluate whether the implanted electrodes provide a neural response or not. This can be used for the early development of vestibular implants to improve gravitoinertial acceleration sensation.

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.

Directional sound sensitivity in utricular afferents in the toadfish Opsanus tau.

The inner ear of fishes contains three paired otolithic end organs, the saccule, lagena and utricle, which function as biological accelerometers. The saccule is the largest otolith in most fishes and much of our current understanding on auditory function in this diverse group of vertebrates is derived from anatomical and neurophysiological studies on this end organ. In contrast, less is known about how the utricle contributes to auditory functions. In this study, chronically implanted electrodes were used, along with neural telemetry or tethers to record primary afferent responses from the utricular nerve in free-ranging and naturally behaving oyster toadfish Opsanus tau Linnaeus. The hypothesis was that the utricle plays a role in detecting underwater sounds, including conspecific vocalizations, and exhibits directional sensitivity. Utricular afferents responded best to low frequency (80-200 Hz) pure tones and to playbacks of conspecific boatwhistles and grunts (80-180 Hz fundamental frequency), with the majority of the units (∼75%) displaying a clear, directional response, which may allow the utricle to contribute to sound detection and localization during social interactions. Responses were well within the sound intensity levels of toadfish vocalization (approximately 140 SPL dBrms re. 1 µPa with fibers sensitive to thresholds of approximately 120 SPL dBrms re. 1 µPa). Neurons were also stimulated by self-generated body movements such as opercular movements and swimming. This study is the first to investigate underwater sound-evoked response properties of primary afferents from the utricle of an unrestrained/unanesthetized free-swimming teleost fish. These data provide experimental evidence that the utricle has an auditory function, and can contribute to directional hearing to facilitate sound localization.

Patterns of saccular afferent innervation in sciaenids.

In this study, saccular afferent arborization patterns in Atlantic croaker Micropogonias undulatus, red drum Sciaenops ocellatus and spot Leiostomus xanthurus were characterized. Leiostomus xanthurus showed the simplest configuration while M. undulatus displayed the most complex. In addition, hair-cell densities at sites sampled along the rostro-caudal axis of the saccular epithelia correlated with the observed patterns of arborization.

Characterizing the frequency tuning properties of air-conduction ocular vestibular evoked myogenic potentials in healthy individuals.

OBJECTIVE: Inconsistencies regarding frequency tuning of ocular vestibular evoked myogenic potentials (oVEMP) prompted the present study to aim at characterizing frequency tuning of oVEMP in healthy individuals. DESIGN: Normative study. STUDY SAMPLE: The study was conducted to obtain oVEMP responses from 54 healthy individuals in age range of 18-30 years. The responses were acquired for tone-bursts at octave and mid-octave frequencies from 250 to 2000 Hz from the inferior oblique muscle using contralateral electrode placement. The frequencies were compared for amplitude and threshold. RESULTS: oVEMPs were present in 100% of individuals at or below the frequency of 1000 Hz. The responses had maximum amplitude and lowest thresholds at 500 Hz. There were at least two replicable peak-complexes namely n1-p1 and p1-n2. Both these complexes revealed tuning at 500 Hz. Comparison between the two peak-complexes revealed higher amplitudes and lower thresholds for p1-n2 complex. CONCLUSIONS: oVEMPs are tuned to 500 Hz for both peak-complexes, with p1-n2 being more robust. Future studies using the threshold of oVEMP may be better suited to use p1-n2 complex for this purpose, provided vestibular origin of the second complex is proved. Additionally, careful use of tuning property is recommended when evaluating pathological conditions.

A balance of form and function: planar polarity and development of the vestibular maculae.

The mechanosensory hair cells of the inner ear have emerged as one of the primary models for studying the development of planar polarity in vertebrates. Planar polarity is the polarized organization of cells or cellular structures in the plane of an epithelium. For hair cells, planar polarity is manifest at the subcellular level in the polarized organization of the stereociliary bundle and at the cellular level in the coordinated orientation of stereociliary bundles between adjacent cells. This latter organization is commonly called Planar Cell Polarity and has been described in the greatest detail for auditory hair cells of the cochlea. A third level of planar polarity, referred to as tissue polarity, occurs in the utricular and saccular maculae; two inner ear sensory organs that use hair cells to detect linear acceleration and gravity. In the utricle and saccule hair cells are divided between two groups that have opposite stereociliary bundle polarities and, as a result, are able to detect movements in opposite directions. Thus vestibular hair cells are a unique model system for studying planar polarity because polarization develops at three different anatomical scales in the same sensory organ. Moreover the system has the potential to be used to dissect functional interactions between molecules regulating planar polarity at each of the three levels. Here the significance of planar polarity on vestibular system function will be discussed, and the molecular mechanisms associated with development of planar polarity at each anatomical level will be reviewed. Additional aspects of planar polarity that are unique to the vestibular maculae will also be introduced.

Irregular primary otolith afferents from the guinea pig utricular and saccular maculae respond to both bone conducted vibration and to air conducted sound.

This study sought to identify in guinea pig the peripheral sense organ of origin of otolith irregular primary vestibular afferent neurons having a very sensitive response to both air-conducted sound (ACS) and bone-conducted vibration (BCV). Neurons responding to both types of stimuli were labelled by juxtacellular labelling by neurobiotin. Whole mounts of the maculae showed that some vestibular afferents activated by both ACS and BCV originate from the utricular macula and some from the saccular macula - there is no "afferent specificity" by one sense organ for ACS and the other for BCV - instead some afferents from both sense organs have sensitive responses to both stimuli. The clinical implication of this result is that differential evaluation of the functional status of the utricular and saccular maculae cannot rely on stimulus type (ACS vs BCV), however the differential motor projections of the utricular and saccular maculae allow for differential evaluation of each sense organ.

[Inferior vestibular neuritis: diagnosis using VEMP]. / Neuritis des N. vestibularis inferior: Diagnose mittels VEMP-Diagnostik.

Vestibular evoked myogenic potentials (VEMP) are a new method to establish the functional status of the otolith organs. The sacculocollic reflex of the cervical VEMP to air conduction (AC) reflects predominantly saccular function due to saccular afferents to the inferior vestibular nerve. We describe a case of inferior vestibular neuritis as a rare differential diagnosis of vestibular neuritis. Clinical signs were a normal caloric response, unilaterally absent AC cVEMPs and bilaterally preserved ocular VEMPs (AC oVEMPs).

Patterns of dissociate torsional-vertical nystagmus in internuclear ophthalmoplegia.

To explore the patterns and mechanisms of jerky seesaw nystagmus in internuclear ophthalmoplegia (INO), we analyzed the nystagmus patterns in 33 patients with dissociated torsional-vertical nystagmus and INO. In 11 (33%) patients, the nystagmus was ipsiversive torsional in both eyes with vertical components in the opposite directions. In contrast, 18 (55%) patients showed ipsiversive torsional nystagmus with a larger upbeat component in the contralesional eye. Four (12%) patients exhibited ipsiversive torsional nystagmus with a greater downbeat component in the ipsilesional eye. At least one component of contraversive ocular tilt reaction was associated in most patients (30/33, 91%). The patterns of jerky seesaw nystagmus in INO suggest a disruption of neural pathways from the contralateral vertical semicircular canals with or without concomitant damage to the fibers from the contralateral utricle in or near the medial longitudinal fasciculus.

Identifying the affected branches of vestibular nerve in vestibular neuritis.

CONCLUSION: The inner ear monitoring system is useful for identifying the affected branches of the vestibular nerve in cases of vestibular neuritis, providing insight about the interval for the relief of vertigo. OBJECTIVE: This study conducted an inner ear monitoring system including audiometry, and caloric, ocular vestibular evoked myogenic potential (oVEMP), and cervical VEMP (cVEMP) tests in cases of vestibular neuritis for assessing the affected branches of the vestibular nerve. METHODS: Twenty patients with vestibular neuritis underwent caloric, oVEMP, and cVEMP tests. Type I indicates that one of the three tests is abnormal; type II indicates that two test results are abnormal; and type III indicates that no test result is normal. RESULTS: All patients had normal hearing, bilaterally. Nineteen (95%) of 20 patients had abnormal caloric responses, 11 patients (55%) had abnormal oVEMPs, and 5 patients (25%) had abnormal cVEMPs. Restated, of all 20 patients, 8 patients were classified as type I, 9 were type II, and 3 were type III. The mean intervals between presentation and relief of vertigo were significantly different among the three types. One year after treatment, caloric, oVEMP, and cVEMP tests returned to normal responses in three (60%) of five patients.

Melatonin attenuates the vestibulosympathetic but not vestibulocollic reflexes in humans: selective impairment of the utricles.

Melatonin has been reported to decrease nerve activity of medial vestibular nuclei in the rat and is associated with attenuated muscle sympathetic nerve activity (MSNA) responses to baroreceptor unloading in humans. The purpose of this study was to determine if melatonin alters the vestibulosympathetic reflex (VSR) and vestibulocollic reflex (VCR) in humans. In study 1, MSNA, arterial blood pressure, and heart rate were measured in 12 healthy subjects (28 ± 1 yr; 6 men, 6 women) during head-down rotation (HDR) before and 45 min after ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the opposite treatment (melatonin or placebo). Melatonin significantly attenuated MSNA responses during HDR compared with placebo (burst frequency Δ 4 ± 1 vs. Δ 7 ± 1 bursts/min, and total MSNA Δ 51 ± 20 and Δ 96 ± 15%, respectively; P < 0.02). In study 2, vestibular evoked myogenic potentials (VEMP) were measured in 10 healthy subjects (26 ± 1 yr; 4 men and 6 women) before and after ingestion of 3 mg melatonin. Melatonin did not alter the timing of the p13 and n23 peaks (pre-melatonin 13.2 ± 0.4 and 21.3 ± 0.6 ms vs. post-melatonin 13.5 ± 0.4 and 21.4 ± 0.7 ms, respectively) or the p13-n23 interpeak amplitudes [pre-melatonin 22.5 ± 4.6 arbitrary units (au) and post-melatonin 22.7 ± 4.6 au]. In summary, melatonin attenuates the VSR and supports the concept that melatonin negatively affects orthostatic tolerance. However, melatonin does not alter the VCR in humans suggesting melatonin's effect on the VSR appears to be mediated by the utricles.

A-pattern strabismus with overdepression in adduction: a special type of bilateral skew deviation?

BACKGROUND: Skew deviation is an acquired vertical ocular misalignment caused by damage to the prenuclear vestibular inputs to the ocular motor nuclei. A-pattern strabismus often has bilaterally symmetric vertical incomitance and overdepression in adduction (superior oblique overaction) and can be associated with developmental delay, cerebral palsy, hydrocephalus, spina bifida, or posterior fossa or other brainstem disease. The purpose of this study is to describe the ocular motility and torsion findings in patients with A-pattern strabismus and bilateral overdepression in adduction (superior oblique muscle overaction) and to propose a possible brainstem mechanism underlying these observations. RESULTS: Most of the 13 patients identified had other neurologic abnormalities, including spina bifida, hydrocephalus, perinatal stroke, or global delay. Only 2 patients had vertical ocular misalignment in primary gaze. Of the 13, 7 had incomitant vertical tropias during lateral gaze, and 12 had bilateral incyclotorsion documented on fundus examination. Despite having bilateral overdepression in adduction (superior oblique overaction), 11 of the 13 had no difference in vertical ocular misalignment with alternating head tilt rather than reversing hypotropias as would be expected from primary oblique dysfunction. The findings are consistent with damage to the utricular pathways corresponding to the anterior semicircular canal and a resulting posterior canal predominance to the extraocular muscle subnuclei that creates increased tonus to the depressors, bilaterally. CONCLUSIONS: A-pattern strabismus may, in some cases, represent a special form of skew deviation. The ocular motility and clinical findings are consistent with bilateral damage to the utricular pathways corresponding to the anterior semicircular canals rather than bilateral primary superior oblique muscle overaction.

Development of otolith receptors in Japanese quail.

This study examined the morphological development of the otolith vestibular receptors in quail. Here, we describe epithelial growth, hair cell density, stereocilia polarization, and afferent nerve innervation during development. The otolith maculae epithelial areas increased exponentially throughout embryonic development reaching asymptotic values near posthatch day P7. Increases in hair cell density were dependent upon macular location; striolar hair cells developed first followed by hair cells in extrastriola regions. Stereocilia polarization was initiated early, with defining reversal zones forming at E8. Less than half of all immature hair cells observed had nonpolarized internal kinocilia with the remaining exhibiting planar polarity. Immunohistochemistry and neural tracing techniques were employed to examine the shape and location of the striolar regions. Initial innervation of the maculae was by small fibers with terminal growth cones at E6, followed by collateral branches with apparent bouton terminals at E8. Calyceal terminal formation began at E10; however, no mature calyces were observed until E12, when all fibers appeared to be dimorphs. Calyx afferents innervating only Type I hair cells did not develop until E14. Finally, the topographic organization of afferent macular innervation in the adult quail utricle was quantified. Calyx and dimorph afferents were primarily confined to the striolar regions, while bouton fibers were located in the extrastriola and Type II band. Calyx fibers were the least complex, followed by dimorph units. Bouton fibers had large innervation fields, with arborous branches and many terminal boutons.

Does migraine-associated vertigo share a common pathophysiology with Meniere's disease? Study with vestibular-evoked myogenic potential.

To clarify if migraine-associated vertigo (MAV) and Meniere's disease (MD) share a common pathophysiology, vestibular-evoked myogenic potentials (VEMP) were measured in 11 patients with MAV, 11 with unilateral MD and eight healthy subjects. As acoustic stimuli, tone bursts (TB; 250, 500, 1000 and 2000 Hz) were presented. In healthy subjects, 500-Hz TB evoked the largest amplitude. To quantify this tendency, 500-1000 VEMP slope was calculated, and 500-1000 VEMP slope was the smallest on the affected side of MD patients. Among the 11 MD patients, five had significantly decreased 500-1000 VEMP asymmetry (shift of the tuning to 1000 Hz). Three of the 11 MAV patients also showed a significantly decreased 500-1000 VEMP slope. This finding suggests that MAV might share a common pathophysiology with MD. In addition to this finding, four of the other eight MAV patients showed prolonged p13 latencies. This suggests that MAV could consist of patients with different lesion sites.

Vestibular evoked myogenic potentials: an overview.

UNLABELLED: The vestibular evoked myogenic potential (VEMP) test is a relatively new diagnostic tool that is in the process of being investigated in patients with specific vestibular disorders. Briefly, the VEMP is a biphasic response elicited by loud clicks or tone bursts recorded from the tonically contracted sternocleidomastoid muscle, being the only resource available to assess the function of the saccule and the lower portion of the vestibular nerve. AIM: In this review, we shall highlight the history, methods, current VEMP status, and discuss its specific application in the diagnosis of the Ménière's Syndrome.