How does high-frequency sound or vibration activate vestibular receptors?

The mechanism by which vestibular neural phase locking occurs and how it relates to classical otolith mechanics is unclear. Here, we put forward the hypothesis that sound and vibration both cause fluid pressure waves in the inner ear and that it is these pressure waves which displace the hair bundles on vestibular receptor hair cells and result in activation of type I receptor hair cells and phase locking of the action potentials in the irregular vestibular afferents, which synapse on type I receptors. This idea has been suggested since the early neural recordings and recent results give it greater credibility.

Vestibular function after vestibular neuritis.

OBJECTIVE: To measure horizontal semicircular canal function over days, weeks, and months after an acute attack of vestibular neuritis. DESIGN: The video head impulse test (vHIT) was used to measure the eye movement response to small unpredictable passive head turns at intervals after the attack. STUDY SAMPLE: Two patients diagnosed with acute right unilateral vestibular neuritis. RESULTS: There was full restoration of horizontal canal function in one patient (A) as shown by the return of the slow phase eye velocity response to unpredictable head turns, while in the other patient (B) there was little or no recovery of horizontal canal function. Instead this second patient generated covert saccades during head turns. CONCLUSION: Despite the objective evidence of their very different recovery patterns, both patients reported, at the final test, being happy and feeling well recovered, even though in one of the patients there was clear absence of horizontal canal function. The results indicate covert saccades seem a successful way of compensating for loss of horizontal canal function after unilateral vestibular neuritis. Factors other than recovery of the slow phase eye velocity are significant for patient recovery.

Does unilateral utricular dysfunction cause horizontal spontaneous nystagmus?

The presence of spontaneous nystagmus in darkness with a strong horizontal component has been taken to indicate that there is asymmetrical function of the horizontal semicircular canals. If this horizontal spontaneous nystagmus can be suppressed by vision, then it is regarded as due to peripheral horizontal canal dysfunction. However, we report evidence from one patient (61-year-old male), who visited the MSA ENT Clinic, Cassino (FR) Italy, reporting acute, severe vertigo, postural unsteadiness, nausea and vomiting associated with right sudden hearing loss. The patient received instrumental audiovestibular testing to obtain objective measurements of his inner-ear receptors. At the time of the attack, the patient showed spontaneous nystagmus, mainly with horizontal and vertical components (3D infrared video-oculography). Video head-impulse tests of dynamic horizontal canal function showed that the functional status of both horizontal canals was within the normal range. Cervical VEMPs to 500 Hz bone-conducted vibration at Fz showed normal results; ocular VEMPs to the same stimulus showed a reduced n10 amplitude beneath the left eye, corresponding to the right ear. For this reason, the patient was diagnosed as having right unilateral selective utricular macula lesion due to labyrinthitis. There is considerable evidence of convergence of neural input from the otoliths onto horizontal canal neurons in the vestibular nuclei. The firing of such neurons could reflect either asymmetrical horizontal canal function or asymmetrical utricular function. The problem with this patient was not due to asymmetrical horizontal canal function, but only to asymmetrical utricular function, demonstrated by the results of the oVEMP test.

Phase-locking of irregular guinea pig primary vestibular afferents to high frequency (>250 Hz) sound and vibration.

Phase-locking of cochlear neurons to sound has been of great value in understanding cochlear transduction. Phase-locking has also been reported previously in irregular vestibular afferents, but detailed information about it is sparse. We measured the phase-locking of guinea pig irregular otolithic neurons and canal neurons (after a semicircular canal dehiscence allowed them to respond) to both sound and vibration stimuli. Irregular vestibular afferents from both otoliths and canals have a range of preferred phase angles which systematically increase as frequency is increased from 250 Hz to above 1000 Hz. Surprisingly vestibular afferents show more precise phase-locking than comparable auditory afferents as reported by Palmer and Russell (1986), and they do so up to higher frequencies. This high precision implies a very sharp, fast threshold for evoking an action potential with minimal variability, and so has implications for the current controversy about hair-cell-afferent transmission in the vestibular system. Following recent evidence, we suggest that potassium in the unique type I-calyx synapse may be a major factor in generating this very precise phase-locking.

Ocular vestibular evoked myogenic potentials to bone conducted vibration of the midline forehead at Fz in healthy subjects.

OBJECTIVE: To provide the empirical basis for using ocular vestibular evoked myogenic potentials (oVEMPS) in response to Fz bone conducted vibration (BCV) stimulation to indicate vestibular function in human subjects. To show the generality of the response by testing a large number of unselected healthy subjects across a wide age range and the repeatability of the response within subjects. To provide evidence that the response depends on otolithic function. METHODS: The early negative component (n10) of the oVEMP to brief BCV of the forehead, in the midline at the hairline (Fz) is recorded by surface EMG electrodes just beneath the eyes. We used a Bruel and Kjaer 4810 Mini-Shaker or a light tap with a tendon hammer to provide adequate BCV stimuli to test a large number (67) of unselected healthy people to quantify the individual differences in n10 magnitude, latency and symmetry to Fz BCV. A Radioear B-71 bone oscillator at Fz is not adequate to elicit a reliable n10 response. RESULTS: The n10 oVEMP response showed substantial differences in amplitude between subjects, but is repeatable within subjects. n10 is of equal magnitude in both eyes with an average asymmetry around 11%. The average n10 amplitude for Mini Tone Burst BCV is 8.47microV+/-4.02 (sd), the average latency is 10.35ms+/-0.63 (sd). The amplitude of n10 decreases and its latency increases with age. CONCLUSIONS: oVEMPs are a new reliable, repeatable test to indicate vestibular and probably otolithic function. SIGNIFICANCE: This study shows the optimum conditions for recording oVEMPs and provides baseline values for individual differences and asymmetry. oVEMPs can be measured in senior subjects without difficulty.

Ocular vestibular evoked myogenic potentials in response to bone-conducted vibration of the midline forehead at Fz. A new indicator of unilateral otolithic loss.

If a patient, who is lying supine and looking upward, is given bone-conducted vibration (BCV) of the forehead at the hairline in the midline (Fz) with a clinical reflex hammer or a powerful bone conduction vibrator, short-latency surface potentials called ocular vestibular evoked myogenic potentials (oVEMP) can be recorded from just beneath the eyes. The early negative (excitatory) component (n10) is approximately equal in amplitude for both eyes in healthy subjects, but in patients with unilateral vestibular loss, the n10 component is significantly asymmetrical under the 2 eyes - the n10 component is small or absent under the eye on the side contralateral to the prior unilateral vestibular nerve removal, but of normal amplitude under the eye on the side contralateral to the healthy ear. The n10 component of the oVEMP response to BCV at Fz stimuli reflects vestibular and probably mainly otolithic function via crossed otolithic-ocular pathways, and so n10 asymmetry is a new way of identifying the affected side in patients with unilateral otolithic loss.

In vivo recording of the vestibular microphonic in mammals.

BACKGROUND: The Vestibular Microphonic (VM) has only featured in a handful of publications, mostly involving non-mammalian and ex vivo models. The VM is the extracellular analogue of the vestibular hair cell receptor current, and offers a tool to monitor vestibular hair cell activity in vivo. OBJECTIVE: To characterise features of the VM measured in vivo in guinea pigs, using a relatively simple experimental setup. METHODS: The VM, evoked by bone-conducted vibration (BCV), was recorded from the basal surface of either the utricular or saccular macula after surgical removal of the cochlea, in 27 guinea pigs. RESULTS: The VM remained after vestibular nerve blockade, but was abolished following end-organ destruction or death. The VM reversed polarity as the recording electrode tracked across the utricular or saccular macula surface, or through the utricular macula. The VM could be evoked by BCV stimuli of frequencies between 100 Hz and 5 kHz, and was largest to vibrations between 600 Hz and 800 Hz. Experimental manipulations demonstrated a reduction in the VM amplitude with maculae displacement, or rupture of the utricular membrane. CONCLUSIONS: Results mirror those obtained in previous ex vivo studies, and further demonstrate that vestibular hair cells are sensitive to vibrations of several kilohertz. Changes in the VM with maculae displacement or rupture suggest utricular hydrops may alter vestibular hair cell sensitivity due to either mechanical or ionic changes.

Psychophysiological correlates of the inter-individual variability of head movement control in seated humans.

We recently conducted experiments where 24 seated participants were subjected (with eyes closed) to small amplitude, high-jerk impulses of linear acceleration. Responses were distributed as a continuum between two extremes. The "stiff" participants showed little movement of the head relative to the trunk, whereas the "floppy" participants showed a large head rotation in the direction opposite the sled movement. We hypothesized that the stiff behavior resulted from the spontaneous use of an imagined visual frame of reference and undertook this larger-scale study to test that idea. The distribution along the "stiff-floppy" continuum was compared with the scores on psychophysiological tests measuring vividness of imagery, visual field-dependence and motion sickness susceptibility. Multivariate regression analysis revealed that the "stiffness" of individuals was loosely, but significantly related to the vividness of their imagery. However, "stiffness" was not linked to visual field-dependence or motion sickness susceptibility. Even if it explains only 20% of the variance of the data, the increase of "stiffness" with vividness of imagery fits our hypothesis. With eyes closed, stiff people may use imagined external visual cues to stabilize their head and trunk. Floppy people, who are poorer imagers, may rely more on "egocentric", proprioceptive and vestibular inputs.

Sensitivity of the cochlear nerve to acoustic and electrical stimulation months after a vestibular labyrinthectomy in guinea pigs.

Single-sided deafness patients are now being considered candidates to receive a cochlear implant. With this, many people who have undergone a unilateral vestibular labyrinthectomy for the treatment of chronic vertigo are now being considered for cochlear implantation. There is still some concern regarding the potential efficacy of cochlear implants in these patients, where factors such as cochlear fibrosis or nerve degeneration following unilateral vestibular labyrinthectomy may preclude their use. Here, we have performed a unilateral vestibular labyrinthectomy in normally hearing guinea pigs, and allowed them to recover for either 6 weeks, or 10 months, before assessing morphological and functional changes related to cochlear implantation. Light sheet fluorescence microscopy was used to assess gross morphology throughout the entire ear. Whole nerve responses to acoustic, vibrational, or electrical stimuli were used as functional measures. Mild cellular infiltration was observed at 6 weeks, and to a lesser extent at 10 months after labyrinthectomy. Following labyrinthectomy, cochlear sensitivity to high-frequency acoustic tone-bursts was reduced by 16 ± 4 dB, vestibular sensitivity was almost entirely abolished, and electrical sensitivity was only mildly reduced. These results support recent clinical findings that patients who have received a vestibular labyrinthectomy may still benefit from a cochlear implant.

Vestibular responses to sound.

Research into vestibular responses to sound has evolved in four stages. The first, largely the work of Tullio in the 1920s, involved inspection of the eye, head, and postural responses to sound of alert animals with surgical fenestrae into various parts of the bony labyrinth. The second, begun in 1964 by Bickford and his group and continued by our group and then by others in the last 10 years, involves the measurement of evoked myogenic potentials to air-conducted and bone-conducted clicks and tones in normal humans. The third, begun by Mikaelian at about the same time as Bickford and continued by McCue, our group, and others, involves electrophysiological recordings of primary vestibular afferent neuron responses to sound in anesthetized animals. The fourth involves measurements of vestibulo-ocular responses to sound in humans with the Tullio phenomenon. It was begun by Minor and his group in 1998 with the observation that sound-induced nystagmus in humans, the Tullio phenomenon, aligned with the rotation axis of the superior semicircular canal. They then showed a defect in the temporal bone between the apex of the superior semicircular canal and the middle cranial fossa, which was the cause of most, if not all, cases of sound-induced nystagmus. Here some of the key observations made in each of these four stages are reviewed.

Patient and normal three-dimensional eye-movement responses to maintained (DC) surface galvanic vestibular stimulation.

HYPOTHESIS: That disease or dysfunction of vestibular end organs in human patients will reduce or eliminate the contribution of the affected end organs to the total eye-movement response to DC surface galvanic vestibular stimulation (GVS). BACKGROUND: It was assumed that DC GVS (at current of 5 mA) stimulates all vestibular end organs, an assumption that is strongly supported by physiological evidence, including the activation of primary vestibular afferent neurons by galvanic stimulation. Previous studies also have described the oculomotor responses to vestibular activation. Stimulation of individual semicircular canals results in eye movements parallel to the plane of the stimulated canal, and stimulation of the utricular macula produces changes in ocular torsional position. It was also assumed that the total three-dimensional eye-movement response to GVS is the sum of the contributions of the oculomotor drive of all the vestibular end organs. If a particular vestibular end organ were to be diseased or dysfunctional, it was reasoned that its contribution to the GVS-induced oculomotor response would be reduced or absent and that patients thus affected would have a systematic difference in their GVS-induced oculomotor response compared with the response of normal healthy individuals. METHODS: Three-dimensional video eye-movement recording was carried out in complete darkness on normal healthy subjects and patients with various types of vestibular dysfunction, as diagnosed by independent vestibular clinical tests. The eye-movement response to long-duration bilateral and unilateral surface GVS was measured. RESULTS: The pattern of horizontal, vertical, and torsional eye velocity and eye position during GVS of patients independently diagnosed with bilateral vestibular dysfunction, unilateral vestibular dysfunction, CHARGE syndrome (semicircular canal hypoplasia), semicircular canal occlusion, or inferior vestibular neuritis differed systematically from the responses of normal healthy subjects in ways that corresponded to the expectations from the conceptual approach of the study. CONCLUSION: The study reports the first data on the differences between the normal response to GVS and those of patients with a number of clinical vestibular conditions including unilateral vestibular loss, canal block, and vestibular neuritis. The GVS-induced eye-movement patterns of patients with vestibular dysfunction are consistent with the reduction or absence of oculomotor contribution from the end organs implicated in their particular disease condition.

Morphology of physiologically identified second-order vestibular neurons in cat, with intracellularly injected HRP.

The morphology of horizontal canal second-order type I neurons was investigated by intracellular staining with horseradish peroxidase (HRP) and three-dimensional reconstruction of the cell bodies and axons. Axons penetrated in and around the abducens nucleus were identified as originating from type I neurons by their characteristic firing pattern to horizontal rotation and by their monosynaptic response to stimulation of the ipsilateral vestibular nerve. A total of 47 type I neurons were stained. The cell bodies were located in the rostral portion of the medial vestibular nucleus (MVN) and were large or medium sized and had rather elongated shapes and rich dendritic arborizations. The neurons were divided into two groups: those which projected to the contralateral side of the brain stem (type Ic neurons) and those which projected to the ipsilateral side of the brainstem (type Ii neurons). All stem axons of type Ic neurons crossed the midline and bifurcated into rostral and caudal branches in the contralateral medial longitudinal fasciculus (MLF). Two or three collaterals arising close to this bifurcation distributed terminals in a relatively wide area in the contralateral abducens nucleus. Some of these collaterals projected further to the contralateral MVN and thus are vestibular commissural axons. Some of the rostral and caudal stem axons had collaterals which projected to the contralateral nucleus prepositus hypoglossi (PH), nucleus raphe pontis, or medullary reticular formation. There were at least six classes of type Ii neurons, most of which distributed to a relatively limited region in the ipsilateral abducens nucleus and they were categorized according to their future projections into the following categories: A) no further collaterals beyond the abducens nucleus; B) collaterals in the abducens nucleus and a branch descending and terminating in ipsilateral PH; C) projected to the abducens nucleus, PH, and an area rostral to the abducens nucleus; D) projected to the abducens nucleus and to ipsilateral reticular formation rostral and caudal to the abducens nucleus; E) collaterals in the abducens nucleus and a thick caudal stem axon entering and descending in ipsilateral MLF; F) a thick caudal stem axon entering and descending in ipsilateral MLF and no collaterals to the abducens nucleus. Some type Ii neurons also had recurrent collaterals which projected back to the ipsilateral MVN; these may inhibit type II neurons during ipsilateral rotation.

Anatomy of physiologically identified eye-movement-related pause neurons in the cat: pontomedullary region.

Pause neurons (PNs) are inhibitory neurons close to the midline at the pontomedullary junction that fire tonically and then cease firing just prior to quick eye movements of visual or vestibular origin. Previous physiological evidence has shown that these neurons have a role of central importance in the generation of rapid eye movements in any direction and all major models of ocular motor control incorporate PNs as major elements. In this study in cats, we injected horseradish peroxidase intracellularly into somata or axons of physiologically identified PNs. After appropriate tissue preparation, cell body and axonal reconstructions were performed, with the aid of a camera lucida-equipped microscope. Fifty-three PNs were stained and reconstructed. These consisted of 17 cell bodies and dendrites and 36 axons. Seven of these included both cell bodies and axons. PN somas lay close to the midline in the nucleus raphe pontis and centralis superior, had extensive dendritic arborizations tending to arise from either pole of the elongated soma, and had axons which typically crossed the midline and bifurcated into long branches which extended rostrally and caudally, inferior to the medial longitudinal fasciculus. There were major terminal arborizations and boutons in areas just rostral and caudal to the abducens nucleus in areas where two types of premotor neurons, excitatory and inhibitory burst neurons, are concentrated. Many axosomatic contacts were noted. Other terminal arborizations and boutons were found close to the midline in a region rostral to abducens nucleus containing other neurons known to burst prior to quick eye movements, and in the nucleus reticularis gigantocellularis. Rostral stem axons could be traced to the level of the trochlear nucleus and inferior to the medial longitudinal fasciculus. The caudal stem axons could be traced parallel to the midline and inferior to the medial longitudinal fasciculus and as far caudally as the hypoglossal nucleus.

Anatomical evidence of the projection of pontine omnipause neurons to midbrain regions controlling vertical eye movements.

Both anatomical and physiological studies have shown that pause neurons (PNs) in the medial pontine reticular formation project to two groups of burst neurons (BNs) involved in the genesis of horizontal saccadic eye movements: The excitatory burst neurons (EBNs), which lie rostral to the abducens nucleus, and the inhibitory burst neurons (IBNs), which lie caudal to the abducens. This study is concerned with the projection from PNs to a group of vertical BNs in the nucleus of the H field of Forel (H FF) in the caudomedial subthalamus. Three anatomical methods were used to demonstrate this connection. First, intra-axonal horseradish peroxidase (HRP) injection into physiologically identified PN axons demonstrated axonal branching and axonal terminations in and around the H FF. Second, micro-injection of the tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the pontine PN region labelled terminal axons and boutons in the nucleus of the H FF. Third, extracellular pressure injection of HRP into H FF yielded retrogradely labelled pontine PN neurons. These anatomical results confirmed the termination of PNs in areas controlling rapid vertical eye movements as physiologically demonstrated by Nakao et al.: Exp. Brain Res. 70:632-636, '88). This work points to the major role of pontine PNs in the synchronization of BN activity in rapid eye movements in all directions.

A clinical sign of canal paresis.

Unilateral loss of horizontal semicircular canal function, termed canal paresis, is an important finding in dizzy patients. To our knowledge, apart from head-shaking nystagmus, no clinical sign of canal paresis has yet been described and the term derives from the characteristic finding on caloric tests: little or no nystagmus evoked by either hot or cold irrigation of the affected ear. We describe a simple and reliable clinical sign of total unilateral loss of horizontal semicircular canal function: one large or several small oppositely directed, compensatory, refixation saccades elicited by rapid horizontal head rotation toward the lesioned side. Using magnetic search coils to measure head and eye movement, we have validated this sign in 12 patients who had undergone unilateral vestibular neurectomy.

Tonic contraversive ocular tilt reaction due to unilateral meso-diencephalic lesion.

We studied 4 patients with tonic contraversive ocular tilt reactions due to unilateral, paramedian, mesodiencephalic lesions. This is in contrast to the only 2 previously reported patients with ocular tilt reactions due to unilateral mesodiencephalic lesions, each of whom had a paroxysmal ipsiversive ocular tilt reaction. This new finding is considered in the context of previous clinical and experimental data on the various types of ocular tilt reactions that follow stimulation or destruction of the peripheral and central vestibular system. Otolithic inputs to the interstitial nucleus of Cajal from the contralateral vestibular nucleus and motor outputs from the interstitial nucleus of Cajal to cervical and ocular motoneurons could be involved in the ocular tilt reaction. We propose that in patients with unilateral meso-diencephalic lesions, a tonic contraversive ocular tilt reaction could be due to persistently decreased resting activity of ipsilateral interstitial nucleus neurons, whereas a paroxysmal ipsiversive ocular tilt reaction could be due to transiently increased activity of the same interstitial nucleus neurons. Cases of ocular tilt reaction due to unilateral meso-diencephalic lesion point to the existence of a crossed graviceptive pathway between the vestibular nucleus and the contralateral interstitial nucleus of Cajal.

Posterior semicircular canal nystagmus is conjugate and its axis is parallel to that of the canal.

A patient with a postoperative fistula of the left posterior semicircular canal is presented. Negative pressure in the external ear canal produced upbeat-torsional nystagmus, which was recorded in three dimensions using binocular scleral search coils. The nystagmus was conjugate, without skew deviation, and its trajectory corresponded to the anatomic axis of the left posterior canal. The current study helps validate Ewald's first law in humans: the axis of nystagmus should match the anatomic axis of the semicircular canal that generated it. This law is clinically useful in diagnosing pathology of the vestibular end-organ, such as benign paroxysmal positional vertigo or the superior semicircular canal dehiscence syndrome.