Quantification of the vestibulo-ocular reflex and visual-vestibular interaction for the purpose of clinical diagnosis.
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Animals↗
Biomedical subjects
B Larsby
Publications and source records attributed to B Larsby.
Vestibular and oculomotor disturbances caused by industrial solvents.
Hydrocarbon solvents, xylene, styrene, methylchloroform, and trichlorethylene, given intravenously to rabbits produce a positional nystagmus. Due to their additional influence on rotatory nystagmus, one may conclude that their mode of action takes place in the central nervous system. Optokinetic (OKN) responses in rabbits, cats, and humans were also influenced by styrene. OKN responses have not yet been tested for the other solvents. A comparison is made with the effects of alpha-chloralose and the GABA-antagonists bicuculline and picrotoxin which produced similar disturbances. The GABA agonist, baclofen, prevents positional induced styrene nystagmus. It seems likely therefore that the solvents may act by blocking the cerebellar inhibition of vestibulo-oculomotor reflexes. Solvents given simultaneously in some combinations are either additive or synergistic in effect. The implications of these results for occupational medicine are self-evident.
Animals↗
The influence of trichloroethylene and related drugs on the vestibular system.
A previously described experimental model for studying the effect of industrial solvents on the vestibular system of rabbits has been applied to trichloroethylene. Estimation of trichloroethylene and its metabolites in blood and cerebrospinal fluid was performed by gas chromatography. Vestibular function was studied by recording nystagmus, induced by positional changes or accelerated rotation. At blood levels of trichloroethylene above 30 p.p.m. "positional nystagmus" develops. Two metabolites of trichloroethylene, chloral hydrate and trichloroethanol, which are known as central nervous system (CNS) depressants, did not induce this abnormal nystagmus. However, alpha-chloralose, a derivative of chloral hydrate, induced positional nystagmus and also a markedly exaggerated nystagmus developed during rotatory acceleration. It is suggested that solvents like trichloroethylene elicit vestibular disturbances by stimulation of central subcortical vestibulo-oculomotor connections. The stimulation may be caused by a blockage of inhibitory systems.
Animals↗
On the mechanism of vestibular disturbances caused by industrial solvents.
The industrial solvents xylene, styrene, trichloroethylene and methylchloroform administered to rabbits caused a positional nystagmus and disturbances in the nystagmus response to rotatory acceleration. The positional nystagmus had a beat direction the opposite to positional alcohol nystagmus, which was in similar experiments elicited by methanol, ethanol and propanol. The three alcohols needed a ten times higher blood concentration to cause a nystagmus than the solvents did.
1-Propanol↗
Exposure of rabbits to methylchloroform. Vestibular disturbances correlated to blood and cerebrospinal fluid levels.
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Animals↗
Exposure of rabbits to styrene. Electronystagmographic findings correlated to the styrene level in blood and cerebrospinal fluid.
Objective methods for critically evaluating the toxic effect of industrial solvents are highly desirable. As many of these solvents are suspected to cause vertigo, an animal experimental model was set up for studying the effects of solvents on the vestibular systems. The vestibular function was studied by registration of involuntary eye movements--nystagmus--which are elicited via central vestibulo-oculomotor connections. During exposure to styrene a so-called positional nystagmus was demonstrated that indicated vestibular disturbances. Nystagmus is normally elicited by rotatory acceleration. During exposure to styrene the direction of this rotatory nystagmus was reversed. The incidence of the positional nystagmus correlated well with the blood level of the solvent, measured by gas chromatography. Kinetic studies also demonstrated a rapid equilibration between the level of the solvent in arterial blood and cerebrospinal fluid, and therefore suggested that estimation of the arterial level reliably indicates the level in the central nervous system.
Animals↗
Projection of thalamic neurons to cat primary vestibular cortical fields studied by means of retrograde axonal transport of horseradish peroxidase.
The two vestibular cortical projection areas in the anterior suprasylvian sulcus and post-cruciate dimple regions were defined by evoked potential technique in anaesthetized cats. The thalamic location of neurons with axon terminals in these fields was determined using the method of retrograde axonal transport of horseradish peroxidase. The ascending vestibular pathway appeared to be separated also at the thalamic level, where cells in the ventroposterolateral nucleus were found to project to the post cruciate dimple and cells in the posterior nuclear group to the anterior suprasylvian vestibular cortical fields.
Afferent Pathways↗
Vestibular and somatosensory inflow to the vestibular projection area in the post cruciate dimple region of the cat cerebral cortex.
In anesthetized cats 251 cells within the cortical vestibular projection area, adjacent to the post-cruciate dimple, were analyzed as to their input characteristics employing extracellular recording techniques. The post cruciate dimple vestibular field, which is located in area 3a, has a high degree of convergence between vestibular and peripheral somatosensory input. The latter is not restricted to muscle afferents but includes cutaneous modalities. The functional significance of this vestibular cortical projection field is discussed.
Animals↗
The effect of toluene on the vestibulo- and opto-oculomotor system in rats, pretreated with GABAergic drugs.
Toluene, an aromatic solvent, prolongs the duration of nystagmus induced by a rotatory acceleration or by an optokinetic stimulation in the pigmented rat. Baclofen, an agonist of GABAB receptors, and 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP), an agonist of GABAA receptors are able to block this toluene effect on the vestibular system. On the contrary diazepam, which by itself causes an evident reduction of the duration of acceleratory nystagmus, is not able to block the toluene effect. The results indicate that the toluene effect is related to GABA transmission and that the solvent interacts by a rather receptor specific mechanism of action.
Animals↗
Effects of toluene, styrene, trichloroethylene, and trichloroethane on the vestibulo-and opto-oculo motor system in rats.
The acute effects of inhalation of four solvents on the central vestibular system of rats were analyzed by recording eye movements upon different stimuli. The dose-response relationship was investigated. Optokinetic stimulation was obtained by placing the animals in front of a surrounding visual pattern, moving at different velocities. The slow-phase eye velocity (SPV) of nystagmus was calculated and divided by the stimulus velocity, giving the gain. All the solvents caused a decrease of the gain. Vestibular stimulation was performed on a turntable by an angular acceleration/deceleration in darkness. The SPV and the duration of the post-stimulatory nystagmus were calculated. The shape of the SPV dose-response curves differed among the four solvents. Toluene, styrene, and trichloroethylene prolonged the duration of nystagmus while trichloroethane did not. A conflicting vestibular and optokinetic stimulation was performed by an angular acceleration/deceleration with a surrounding visual pattern moving with the turntable. All solvents decreased the ability to cancel nystagmus, elicited by vestibular stimulation in conflict with a visual input. Quick movements of the eyes, saccades, were elicited by tactile stimulation. Toluene, styrene, and trichloroethylene changed the generation of the saccades while trichloroethane did not. Most of the findings indicate a common site of action in the central vestibular system, viz, the cerebellar-vestibular circuit. However, within this domain, there are evident differences in the effects among the solvents. This findings, together with previous results obtained in other experimental models of the central nervous system (CNS), suggest that different solvents should be considered as individual compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Projection of the vestibular nerve to the SI arm field in the cerebral cortex of the cat.
Evoked cortical focal potentials from electrical vestibular nerve stimulation were recorded in the Pcd-area in cats anaesthetized with Chloralose or Nembutal. For comparison, additional cortical projections were located for n. rad. superficialis and group Ia muscle afferents from n. rad. prof., n. fibularis prof., n. femuralis ramus muscularis and the motor nerve to the trapezoid muscle. Surface positive potentials, which reversed to negativity in middle cortical layers, were for vestibular nerve stimulation recorded in the S I forelimb field in a small area close to Pcd in the posterior medial part of the deep radial nerve projection field. The location of this field is compared with the vestibulo-cortical projections described earlier for rodents, squirrel monkey, and rhesus monkey. The histology shows that the field was within the cytoarchitectonic 3a area.
Animals↗
Electronystagmographic and gaschromatographic studies in rabbits.
Complaints of vertigo from people who are exposed to industrial solvents have focused interest on their toxic effect on the nervous system. In order to evaluate the influence of an organic solvent, xylene, on the mammalian vestibular system, a series of rabbit experiments were performed. To achieve a constant concentration, the xylene was infused as a lipid emulsion. Blood concentrations were estimated by gas chromatography. Electronystagmography in darkness revealed that at blood xylene concentrations of 30 ppm all rabbits had a positional nystagmus. The beat direction was the opposite of positional alcohol nystagmus. Another difference between the alcohol and the xylene reaction was that rotatory nystagmus responses were exaggerated. The relations between the present findings and the reactions and blood concentrations in people exposed to industrial solvents are discussed.
Aerosols↗
Limb input to the cat vestibular nuclei.
The input from fore- and hindlimbs to the vestibular nuclear complex (VNC) was investigated in awake cats. Electrical stimulus was given to the sciatic, radial and vestibular nerves bilaterally and single unit responses were recorded in the VNC with extracellular technique. The position of the microelectrode was histologically confirmed. All four major vestibular nuclei received fore- as well as hindlimb input. Forty per cent of the neurons with limb input also received vestibular afferents. No major distinguishing features appeared between the different nuclei with regard to response characteristics. Certain differences in laterality of response, quantitative fore-hindlimb ratio and somatosensory-labyrinthine convergence were observed however. Response latencies to sciatic and radial nerve stimuli always exceeded a 3 msec and were grouped around 8 and 16 msec. A third population of vestibular neurons had latencies over 20 msec. Both excitatory and inhibitory responses were recorded, with the latter not always following an activation. The findings illustrate the complex nature of the ascending pathway to the VNC and the integrative properties of this complex.
Action Potentials↗
Vestibulo-oculomotor disturbances in humans exposed to styrene.
Several reports indicate that disturbances of the vestibulo-oculomotor ability are a manifestation of the toxic action on the central nervous system exerted by some industrial solvents. The aim of the present investigation was to examine the vestibulo-oculomotor system during exposure to styrene, which is extensively used in the production of plastics. Healthy volunteers were exposed to styrene for one hour. Rotatory and optokinetic nystagmus, visual suppression as well as speed, latency and accuracy of saccades were tested before, during, and one hour after the exposure. The pulmonary uptake and the blood level of the solvent were continuously analysed by gas chromatography. The styrene blood concentration was equivalent to that which may well be reached after serveral hours of hard work in an industrial environment with a concentration of styrene within permitted limits. No spontaneous nystagmus appeared. The rotatory and optokinetic nystagmus was not influenced by styrene. However, the speed of the saccade was significantly enhanced. The visual suppression was disturbed, shown by an increased gain after styrene exposure. The experiments thus indicate that styrene given to healthy test persons induced disturbances, thus consistent with the theory that some organic solvents block the cerebellar inhibition of the vestibulo-oculomotor system.
Adult↗
Electronystagmographic findings in rats exposed to styrene or toluene.
A previously described experimental model for studying the effect of industrial solvents in the vestibular system of rabbits has been applied to rats. To achieve a constant concentration, the solvent was infused intravenously, dissolved in a lipid emulsion. Arterial blood levels were estimated by gas chromatography. The vestibulo-oculomotor behaviour of rats during repeated rotatory acceleration was investigated by electronystagmography. The effect of two solvents-toluene and styrene-on the rotatory induced nystagmus was examined. Both solvents caused an exaggerated reaction at arterial blood levels above 75 ppm. The investigation indicated that the rat will be suitable species for further electronystagmographic investigation of the influence of organic solvents on the vestibular system, for example in screening studies of the toxicity of these solvents.
Animals↗
Quantification of slow compensatory eye movements in patients with bilateral vestibular loss. A study with a broad frequency-band rotatory test.
Seven patients with bilateral vestibular dysfunction were investigated with a new broad frequency oscillatory test. The vestibular stimulation was of two types: a pseudo-random oscillation in the frequency range 0.5-4 Hz and a sinusoidal frequency sweep from 0.5 to 3.5 Hz. Compensatory eye movements were recorded by EOG. Gain and phase values between eye and head movements were extracted using power spectral analysis technique. Two different visual conditions were used: 1) fixating a stationary target and /) fixating a moving target (visual suppression test). At high frequencies all patients showed a reduced VOR gain compared to normal subjects. At low frequencies gain values were close to normal when using a predictable (sinusoidal) stimulation. With a non-predictable (pseudo-random) stimulation gain values were significantly reduced even at low frequencies. The patients with the most severe loss showed a phase lag at higher frequencies (condition 1). The results in the oscillatory test were compared to subjective symptoms and caloric responses. The new test appears to be better suited to assess the vestibular function in patients with suspected bilateral vestibular loss than the caloric test or other traditional procedures.
Adult↗
Gain and phase characteristics of compensatory eye movements in light and darkness. A study with a broad frequency-band rotatory test.
Thirteen normal subjects were investigated with a broad frequency-band (up to 4.5 Hz) rotatory test. The vestibular stimulation consisted of either a pseudo-random or a sinusoidal frequency sweep oscillation. Eye movements were recorded by EOG. Head movements were recorded either by a potentiometer attached to the chairs axis of rotation or by an angular rate sensor attached to a biteboard . Gain and phase values between eye and head movements were calculated. Measurements were performed in light and darkness during the execution of various fixation tasks. In the higher frequency range there was a in gain and phase between potentiometer and rate sensor measurements due to movement of the head relative to the headholder . Visual suppression, in agreement with earlier studies, was more effective during a sinusoidal stimulation than during a pseudo-random stimulation at low frequencies, using the more precise rate sensor measurement technique. Different instructions in the dark could alter the gain values at lower frequencies (up to 2 Hz) during sinusoidal stimulation. During pseudo-random stimulation no such differences could be elicited. Under all test conditions with the rate sensor, the gain values approached unity at about 3 Hz.
Adolescent↗
The effect of toluene on the vestibulo- and opto-oculomotor system in rats. A computerized nystagmographic study.
The short-term effect of exposure to toluene on the vestibulo- and opto-oculomotor system in rats was investigated. Stimulation of the vestibulo- and opto-oculomotor system was either a constant rotatory acceleration, a sinusoidal oscillation, a randomized oscillation or an optokinetic stimulation. Eye movements in response to the different stimulations were recorded by EOG and fed into a computer for analysis. Due to toluene exposure the slow phase velocity gain during constant acceleration increased and the post-acceleratory nystagmus response was prolonged. The optokinetic gain at stimulation velocities above 10 deg/sec decreased during toluene exposure. Toluene also prolonged the duration of optokinetic after- and after-afternystagmus. The findings in this study strongly suggest an effect of toluene on the cerebellum.
Acceleration↗