15 healthy volunteers were investigated in a vestibulo-oculomotor test battery during toluene exposure. The concentration was comparable to the threshold limit value. The results were compared to an identical air experiment. The intoxication caused an impaired visual suppression during a pseudo-random oscillatory swing test and also an increased saccade speed. Other vestibular-oculomotor parameters were normal. The findings are in accordance with our earlier study on styrene in humans, showing that the visual suppression test and the saccade test are sensitive parameters assessing neurotoxic influences by organic solvents.

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.

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.

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.

In awake cats cells forming the lateral (LVST) and medial (MVST) vestibulospinal tracts were identified by employing antidromic stimulation of the spinal cord. Neuronal responses to bilateral vestibular, forelimb, hindlimb, and neck electrical nerve stimulation were analysed. Extracellular recording in the vestibular nuclei was performed via a glass micropipette saturated with Fast Green, to aid in later histological tract identification. The number of cells projecting to cervical and lumbar regions in the dorsal and ventral division of Deiters' nucleus did not differ significantly. An unexpectedly large number of MVST units was found in the descending nucleus. Some MVST units projected to the lumbar cord but in both the medial and descending nuclei, projections to the cervical cord were in majority. Almost all spinal projecting vestibular neurons received labyrinthine input and more than half received somatosensory input. The units could be separated into several populations on basis of excitatory and inhibitory labyrinthine response latencies indicating multiple pathways. As regards labyrinthine-somatosensory integration the two tracts were found to be quite similar. The extent and complexity of labyrinthine-somatosensory convergence indicate the importance of feed-back mechanisms upon postural controls also at the level of the vestibular nuclei.

The labyrinthine input to the vestibular nuclei was investigated in 24 awake cats. Stimulus consisted of electrical shocks given through bipolar silver wire electrodes, implanted in the utricular and lateral ampullar nerves. Throughout the vestibular nuclei, single units were recorded extracellularly with glass micropipettes filled with Fast Green. The tracts of the penetrating electrodes were identified histologically. In all four nuclei units responding to both labyrinths outnumbered unilaterally responding neurones with certain differences between the individual nuclei. Excitatory as well as inhibitory responses were observed, polysynaptic being more common than mono- or disynaptic ones. No monosynaptic contralateral responses were seen. The latency distribution of contralateral responses closely mirrored that of ipsilateral responses within each nucleus. Both excitatory and inhibitory responses fell into relatively segregated populations, based upon latency distribution. This implies separate pathways for labyrinthine input to the vestibular nuclei.

The vestibulo-thalamic projection was investigated in anaesthetized cats. Electrical stimulation of posterolateral thalamic areas frequently changed the spontaneous firing pattern of neurons in the vestibular nuclei but only 5% were antidromically invaded. This group was further analysed with regard to types of labyrinthine and somatosensory input; thalamo-projecting neurons in the vestibular nuclei are frequently located in the lateral vestibular nucleus, they receive no monosynaptic inflow from the labyrinth and they often receive convergent vestibular and somatosensory input.

1. In awake squirrel monkeys the thalamus was investigated for neuronal responses to vestibular, auditory, visual, proprioceptive, and exteroceptive somatosensory stimulation. The vestibular representation in the thalamus was focused.2. Units responding to electrical vestibular stimulation were found to be scattered within thalamic nuclei receiving somatosensory afferents.3. Ventrobasal neurons have previously been considered place and modality specific. The present data suggest exceptions to this belief. Vestibular input converges with somatotopically organized proprioceptive afferents on neurons in the nucleus ventralis posterior lateralis, pars oralis (identical to nucleus ventralis intermedius), as well as in the posterior portion of the caudal part of the same nucleus. Convergence of both modalities was also found in other nuclei, mainly belonging to the posterior nuclear group, where auditory convergence was also demonstrated.4. Of the vestibular cells in the nucleus ventralis posterior lateralis, 23% projected to the sensorimotor cortex, some with collaterals to both pre- and postcentral gyri.

In anesthetized squirrel monkeys vestibular representation in the thalamus and basal ganglia was determined by field potential recording using peripheral electrical vestibular nerve stimulation. Vestibular thalamic regions were investigated for cortical connections. Two relatively large thalamic areas, nucleus ventralis posterolateralis, VPL and the posterior nuclear group (Po) received vestibular inputs with short latencies suggesting direct connections with the vestibular nuclei. Antidromic stimulation of the area 3a vestibular field did not produce responses in any of the vestibular thalamic fields. The vestibular regions in VPL and Po can be antidromically invaded from SI and the anterior parietal lobe respectively. In the striatum vestibular fields were found in the suprathalamic portion of the nucleus caudatus and dorsomedially in the putamen.