In recent years, several monoamines and neuropeptides have been shown to act as neuromodulators in the vestibular system. This review focuses on the modulatory effects of monoamines including noradrenaline, dopamine, and serotonin, and peptides including somatostatin, opioid peptides, adrenocorticotropin, and tachykinins, on the neuronal activity of the central vestibular nuclei neurons, as well as the receptor subtypes involved in the effects induced by each of the monoamines or peptides. In vivo or in vitro electrophysiological studies have demonstrated that each of these monoamines or peptides inhibits, excites, or has both excitatory and inhibitory effects on the neuronal activity of vestibular nuclei neurons. However, there have been some discrepancies between the data obtained from electrophysiological studies and those by immunohistochemical or molecular biological works. In addition, although a few in vitro electrophysiological studies have tried to elucidate the mechanisms underlying the effects induced by monoamines, most of the ionic mechanisms as well as the site of action or the second messenger systems involved remain unidentified. Since recent works have suggested that some neurotransmitter-dependent conductances play roles in the central processing of vestibular inputs, and that the vestibular system can be used as a good model to elucidate some of the basic properties of the brain including learning, neural computation, network reconfiguration and post lesioned plasticity, the information on the detailed mechanisms underlying the modulatory effects induced by monoamines or peptides would be valuable not only for the understanding of the vestibular system but also for the treatment of the syndromes related to the vestibular system.
Various drugs are known to be toxic to the vestibular endorgan. Aminoglycosides are the best known among those. The action of aminoglycosides are two fold; one is direct inhibition of the ion channels on the cell surface, and the other is metabolic inhibition of phosphatidylinositol in the cell. The patterns of morphological damage have been well documented. The central portions of the crista ampullaris and the striola are more vulnerable to ototoxicity than other portions. Physiological effects of ototoxic drugs were studied using an isolated semicircular canal model. Injection of the drugs into the perilymphatic space resulted in marked inhibition of the ampullary nerve potential, indicating that the drug acts on the basal membrane rather than inhibiting the ion channels of the cell surface. Dizziness induced by ototoxic drugs is characterized by various symptoms, such as persistent dizziness, the jumbling phenomenon, and disturbance of the righting reflex. Since medication has very little effect on dizziness, prevention should be given the top priority. Regular follow-up of hearing as well as vestibular function is mandatory for preventing future ototoxic side effects.
Yates has reported that serotonin neurons in the raphe nuclei are associated with vestibulo-sympathetic responses and may possibly control BP changes during body replacement. Pompeiano demonstrated that the noradrenaline (NA) neurons in the locus coeruleus (LC) participate in posture control and modify the vestibulo-spinal reflex. In our studies, LC-NA neuronal activity was inhibited by vestibular caloric stimulation, which causes vertigo clinically in humans. The vestibular input may be modified by the ventrolateral medulla (VLM) and then inhibit LC neuronal activity via GABAA receptors. Simultaneously, the VLM, the cardiovascular center in the brainstem, may change BP during vestibular stimulation. Thus, it is suggested that LC-NA inhibition is involved in the development of vertigo. Moreover, it is speculated that sopite syndrome, one of the major symptom complexes of motion sickness, is also evoked by LC-NA inhibition. The central LC-NA and cholinergic neuron systems participate in vertigo and motion sickness, independent of the histaminergic neuron system. On the other hand, the cholinergic neuron system may mediate LC-NA inhibition during vestibulo-autonomic responses. The LC-NA system projects to most higher centers and affects sensory information processing. Therefore, it is suggested that the suppression of the sensory information processing induced by LC-NA inhibition causes drowsiness, one of the major symptoms of vertigo and motion sickness. It is also speculated that LC-NA inhibition participates in the development of sensory mismatch.
Output from a single semicircular canal during Coriolis stimulus (cross-coupled rotation) was deduced by an approach of mechanics in a previous paper. Based on the estimate of the canal output, the turning sensation derived from the whole semicircular canal system was deduced in this paper. First, the aspect of integration of turning sensations derived from the individual semicircular canals was considered. Neural linkage concerned with the turning sensation from the semicircular canal system was hypothesized to be arranged so as to perceive head rotation having an axis identical to a stimulus motion. Then, turning sensations caused by a single Coriolis stimulus and cyclic Coriolis stimuli were estimated. When presented in the coordinate system fixed in a horizontally rotating device, the magnitude and the direction of turning sensation were shown to depend on the angular velocity of body rotation and the rotating angle of head movement (amplitude of head oscillation in the case of cyclic Coriolis stimuli) irrespective of the initial angle (center angle) of the head relative to the vertical axis. The propriety of the hypotheses produced by the present deduction was discussed.
Paramedian suboccipital transmeatal vestibular neurectomy was performed in 21 cases of intractable vertigo. Nineteen patients had Ménière's disease and two had inner ear disease. The twenty-one patients consisted of 15 males and 6 females with ages ranging from 21 to 61 years old (mean age, 45.9) at the time of operation. Vertiginous attacks ceased in all patients following surgery. Postoperative hearing improved in 5 patients (24%), did not change in 9 (43%), and worsened in 7 (32%). Sixteen of the 21 patients responded to a questionnaire regarding the pre-and postoperative course. According to the results, the operations satisfied all patients except one, in whom postoperative headache continued. Vestibular neurectomy is the treatment of choice to accomplish complete relief from uncontrollable vertigo.
Gene transfer may be applied in a variety of organs, including the inner ear. For experimental purposes, adenoviral vectors have been inoculated into the scala tympani via cochleostomy or the round window membrane, which resulted in transgene expression restricted to the cochlear tissues in the perilymphatic spaces. In the current study, we injected an adenoviral vector expressing the bacterial lacZ reporter gene into the endolymphatic sac of guinea pigs, and observed the distribution of transgene expression. A large number of lacZ-positive cells were present in the endolymphatic duct and sac. LacZ was expressed in the saccule and utricle, as well as in the semicircular canals. In the cochlea, a greater amount of lacZ-positive cells was observed in basal turns compared to more apical turns; the lacZ-positive cells included Hensen cells and strial marginal cells. LacZ was not expressed in the hair cells in either the vestibule or the cochlea, suggesting that transgene expression to the sensory hair cells is difficult to achieve using an adenoviral vector. These findings indicate that inoculation of viral vectors into the endolymphatic sac can provide efficient gene transfer into a variety of cell types that are not accessible via scala tympani inoculation, and can expand the possibility of molecular research and therapy to more inner ear diseases.
In order to clarify the diagnostic significance of eye tracking tests (ETT), optokinetic nystagmus tests (OKN), and visual suppression test (VST) on routine ENG tests, we investigated the findings of ETT, OKN, and VST in 1, 225 patients who complained of vertigo and dizziness, and in 440 of the patients, we compared these findings with MRI abnormalities. Abnormal results of ETT, OKN, and VST were seen in 433 patients (35.1%), 399 patients (32.6%), and 128 patients (10.5%), respectively. All tests showed impairment in 66 patients (5.4%). Both ETT and OKN abnormalities with normal VST were observed in 173 patients (14.1%), while 356 patients (29.1%) had abnormal findings for ETT, OKN, or VST. In the patients who had severely impaired ETT, OKN, or VST, there was a significantly higher proportion of infratentorial lesions on MRI than in the other patients. In the patients with abnormalities on both ETT and OKN, infratentorial le-sions were more frequently found by MRI, and the patients who had abnormalities on all tests had the highest incidence (61.7%) of infratentorial lesions on MRI. We conclude that the evaluation of ETT, OKN, and VST abnormalities should be quite useful in the diagnosis of infratentorial lesions.
Seventy-five patients who complained of vertigo or dizziness were evaluated in this study to clarify the origin of the responses of the vestibular evoked myogenic potentials (VEMP) and usefulness of VEMP for making clinical diagnoses. We compared the findings of VEMP with those of bithermal caloric tests. Responses of the VEMP were related to the maximal slow phase velocity of caloric tests. In some cases, responses of the VEMP differed from CP% of the caloric tests. Furthermore, responses of the VEMP showed age-related change, as previously described in a pathological study in which the saccule showed age-related change. We concluded that VEMP is a test that evaluates vestibular function like a caloric test, but it may also show functions of otoliths such as saccules. Furthermore, VEMP may be a new test for vestibular function, and it may contribute to making an exact diagnosis in vertiginous patients.
We applied a new system that estimates autonomic nerve function during severe nausea arising during caloric vestibular stimulation. We monitored electrocardiograms of twenty-six healthy volunteers and four patients during caloric vestibular stimulation Nine people were stimulated with 6 liters/min of 37°C and 24°C air into each ear at random. Twenty-one people were stimulated with the same amount of air but in the following order: right ear, 24°C; left ear, 24°C; right ear, 50°C; and left ear, 50°C. After caloric vestibular stimulation, eleven people developed severe nausea and they were defined as the severe group. The others were put into the mild group. The coefficient of variation of the 50 R-R intervals (CV) was analyzed by a personal computer in order to be aware of any small changes in autonomic function. No significant change of CV was seen between 24°C and 37°C stimulation. In the mild group, 50°C stimulation resulted in decreased CV, but in the severe group, there was increased CV with 50°C stimulation. A high CV was associated with severe nausea. In conclusion, nausea in caloric vestibular stimulation was associated with increased parasympathetic nervous system activity.
It has been shown that the nucleus of the optic tract (NOT) is an important visuomotor relay between the retina and preoculomotor structures, and is responsible for mediating horizontal optokinetic nystagmus (OKN) in monkeys, cats, rabbits, and rats. The details between the NOT and the vestibular nucleus in the brain stem concerning the morphology of fibers-of-passage and axon terminals have been disclosed in cats and monkeys. One is that they project to the contralateral NOT via the posterior commissure. In order to evaluate the role of the commissural fibers between the NOTs, the posterior commissure was cut in the present experient. Three fuscata monkeys (M17, M19, M22) were used. A magnetic search coil was sutured to the right eye to record eye position. Several bolts were embedded and secured with dental acrylic cement to fasten the animal's head during experiments. The animal was mounted on a turn table covered by an OKN screen, onto which OKN stripes were projected from above. The animals viewed the OKN stripes under three conditions: right eye viewing, left eye viewing, and bilateral eye viewing. OKN was recorded in response to counter clockwise (CCW) and clockwise (CW) stimulation at stimulus velocities of 30°/s, 60°/s, and 90°/s. After the control experiment was completed, the posterior commissure was transected by an operator knife. After follow-up studies were completed, an anterograde tracer was injected in the left NOT to ascertain the complete block between NOTs. Rapid rise (RR) and steady state (SS) of slow-phase OKN velocity and time-constants (TC) of optokinetic afternystagmus (OKAN) were measured. In three aniamis, OKN gains elicited with monocular viewing were approximately equal to the those of binocularly-evoked OKN before and after surgery. In the three monkeys, the commissurectomy decreased RR and SS to both sides during the three weeks immediately after surgery. In M22, TC showed the tendency to decrease by only 30°/s and 60°/s after surgery. There were no significant differences in TCs of other experiments. In conclusion, gain reduction in RR and SS can be explained by decrease of inhibiting the resting rate in NOT, which is conducted via commissural fibers. This was caused by interruption due to a middle-line lesions. Furthermore, interrupting the commissural fibers has nothing to do with the velocity storage mechanism.