Characterization of the vestibulo-ocular reflex evoked by high-velocity movements.

OBJECTIVES/HYPOTHESIS: The horizontal angular vestibulo-ocular reflex (VOR) plays an important role in stabilizing images on the retina throughout head rotations. Current evidence suggests that the VOR behaves linearly at low velocities and nonlinearly at high velocities. The aim of the research was to evaluate and characterize the normal behavior of the reflex evoked by high-velocity head rotations. STUDY DESIGN: Case control study. METHODS: Manually applied head-thrust movements with peak velocities in the range of 100degrees to 500degrees/s and peak accelerations up to 7,000degrees/s were performed on normal volunteers. These head thrusts were comparable with those described in detail by Halmagi and coworkers. Eye and head movements were recorded using the magnetic search coil method. RESULTS: The gain of the VOR is linear at low velocities and saturates at head velocities greater than 350degrees/s. The values for the normal gain of the reflex were approximated by means of the area between two nonlinear functions. The directional difference parameter, exploring the symmetry of the reflex, indicated that the VOR in normal subjects is symmetric. CONCLUSION: The gain of the VOR in individuals with intact vestibular function is nonlinear at high angular head velocities. We propose a quantitative means using two nonlinear functions to characterize the normal range of values for the gain of the VOR in individuals with normal vestibular function. A directional difference parameter used in conjunction with the normal range of gains can detect small differences in the symmetry of the VOR and, consequently, reveal unilateral vestibular loss.

Asymmetric integration recorded from vestibular-only cells in response to position transients.

Angular and translational accelerations excite the semicircular canals and otolith organs, respectively. While canal afferents approximately encode head angular velocity due to the biomechanical integration performed by the canals, otolith signals have been found to approximate head translational acceleration. Because central vestibular pathways require velocity and position signals for their operation, the question has been raised as to how the integration of the otolith signals is accomplished. We recorded responses from 62 vestibular-only neurons in the vestibular nucleus of two monkeys to position transients in the naso-occipital and interaural orientations and varying directions in between. Responses to the transients were directionally asymmetric; one direction elicited a response that approximated the integral of the acceleration of the stimulus. In the opposite direction, the cells simply encoded the acceleration of the motion. We present a model that suggests that a neural integrator is not needed. Instead a neuron with a long membrane time constant and an excitatory postsynaptic potential duration that increases with the firing rate of the presynaptic cell can emulate the observed behavior.

Linearity of canal-otolith interaction during eccentric rotation in humans.

During natural behavior, the head may simultaneously undergo rotation, transduced by the semicircular canals, and translation, transduced by the otolith organs. It has been demonstrated in monkey that the vestibulo-ocular reflexes (VORs) elicited by both endorgans (i.e., the angular and linear VORs, or AVOR and LVOR) sum linearly during combined rotation and translation, but this finding has proven more elusive in humans. To investigate the combined AVOR/LVOR response, six human subjects underwent yaw eccentric rotation at 3 Hz in darkness while displaced from the axis of rotation. Responses to on-center yaw rotation (AVOR alone) and interaural translation (LVOR alone) were also recorded. During eccentric rotation with the subject facing away from the axis of rotation (i.e., nose out), in which a yaw to the right occurs simultaneously with a translation to the right (i.e., translation in phase with rotation), the AVOR and LVOR acted synergistically. Responses were always out of phase with rotation, and became larger in magnitude as vergence increased. For nose-in eccentric rotation, during which translation is out of phase with rotation, the LVOR acted antagonistically to the AVOR. During near viewing, the LVOR often dominated the overall response when eccentricity was sufficiently large, producing eye movements that were in phase with the rotational stimuli. As vergence decreased, the LVOR influence diminished, eventually resulting in responses that were out of phase with rotation at lowest vergence. When the response to pure yaw rotation was vectorially removed from the responses to eccentric rotation, the results proved statistically indistinguishable from the LVOR recorded during interaural translation, suggesting that the ocular response to combined angular and linear motion reflects the linear combination of the AVOR and LVOR.

Opsoclonus in three dimensions: oculographic, neuropathologic and modelling correlates.

Opsoclonus is a dyskinesia consisting of involuntary, arrhythmic, chaotic, multidirectional saccades, without intersaccadic intervals. We used a magnetic scleral search coil technique to study opsoclonus in two patients with paraneoplastic complications of lung carcinoma. Eye movement recordings provided evidence that opsoclonus is a three-dimensional oscillation, consisting of torsional, horizontal, and vertical components. Torsional nystagmus was also present in one patient. Antineuronal antibody study revealed the presence of anti-Ta (Ma2 onco-neuronal antigen) antibodies in one patient, which had previously been associated only with paraneoplastic limbic encephalitis and brainstem dysfunction, but not opsoclonus, and only in patients with testicular or breast cancer. Neuropathologic examination revealed mild paraneoplastic encephalitis. Normal neurons identified in the nucleus raphe interpositus (rip) do not support postulated dysfunction of omnipause cells in the pathogenesis of opsoclonus. Computer simulation of a model of the saccadic system indicated that disinhibition of the oculomotor region of the fastigial nucleus (FOR) in the cerebellum can generate opsoclonus. Histopathological examination revealed inflammation and gliosis in the fastigial nucleus. This morphological finding is consistent with, but not necessary to confirm, damage to afferent projections to the FOR, as determined by the model. Malfunction of Purkinje cells in the dorsal vermis, which inhibit the FOR, may cause opsoclonus by disinhibiting it.

Frequency-dependent effects of glutamate antagonists on the vestibulo-ocular reflex of the cat.

In the central nervous system, sensory and motor signals at different frequencies are transmitted most effectively by neural elements that have different dynamic characteristics. Dynamic differences may be due, in part, to the dynamics of neurotransmitter receptors. For example, N-methyl-D-aspartate (NMDA) receptors are thought to be a component of the "neural integrator" of the vestibulo-ocular reflex (VOR), which generates a signal proportional to eye position. We measured the effects of blockade of NMDA and AMPA/kainate receptors on the gain and phase of the VOR at frequencies between 0.1 and 8 Hz in alert cats. The competitive NMDA antagonist, APV, and the non-competitive antagonists, MK-801 and ketamine, all caused a pronounced reduction in VOR gain. Gain was more strongly attenuated at low frequencies (0.1-1 Hz) than at higher frequencies (2-8 Hz). The phase lead of the eye with respect to the head was increased up to 30 degrees. In contrast, the reduction in gain associated with drowsiness or surgical anesthesia was not frequency-dependent. Blockade of AMPA/kainate receptors by the competitive antagonists, CNQX and NBQX, reduced the gain of the VOR at all frequencies tested. We evaluated our results using a control systems model. Our data are consistent with participation of NMDA receptors in neural integration, but suggest that NMDA receptors also participate in transmission by other components of the VOR pathway, and that neural integration also employs other receptors. One possibility is that between 0.1 and 10 Hz, higher-frequency signals are transmitted primarily by AMPA/kainate receptors, and lower frequencies by NMDA receptors. This arrangement would provide a biological substrate for selective motor learning within a small frequency range.

Click evoked EMG responses in sternocleidomastoid muscles: characteristics in normal subjects.

Recordings were obtained from a total of 25 normal subjects of the electromyographic (EMG) responses in the sternocleidomastoid muscle (SCM) to intense sound stimuli. While previous authors have demonstrated these responses exist, it has remained unclear whether the EMG response is unilateral or bilateral in nature. Accordingly, we chose a remote site, linked-wrists, for our reference electrodes so that we could be certain that no significant volume conduction of potentials could occur from the source in the SCM to the reference site. When this was done we found that if the sternum was used as a reference site, as was the case in previous studies, some subjects exhibited bilateral responses while in others, the response was ipsilateral. However, with linked-wrists as the reference site, responses were always purely ipsilateral. Furthermore, recordings that used the sternum or the ipsilateral mastoid process as active sites and linked-wrists as a reference, exhibited responses which were inverted. Thus, both the sternum and the ipsilateral mastoid process are electrically active due to volume conduction from the nearby source in the SCM. The ambiguity in previous recordings can be attributed to the use of these active sites as a reference. When SCM responses are recorded versus a remote, electrically inactive site, the responses are purely ipsilateral.

Model for the translational vestibuloocular reflex (VOR).

The function of the translational vestibuloocular reflex (tVOR) and the angular vestibuloocular reflex (aVOR) is to stabilize images on the retina during translational and rotational motion, respectively. It has generally been assumed that these two reflexes differ in their central processing because they differ significantly in their primary afferent behavior and characteristics at the motor level. So far, models of the tVOR have focused on the type of processing that the primary afferent signal must undergo before reaching the neural integrator. Here, we propose a model that does not require any prefiltering. It is known that the eye plant requires signals in phase with velocity and position. We propose that the velocity signal is obtained directly from the neural integrator, whereas the position signal is obtained directly from the primary afferents synapsing onto the oculomotor nuclei. This design proved sufficient to simulate eye movements in response to translational motion.

Vestibulo-ocular reflex deficits to rapid head turns following intratympanic gentamicin instillation.

The response of the vestibulo-ocular reflex following unilateral vestibular deafferentation by gentamicin ablation was studied using transient stimuli. The response to these rapid passive head turns showed a strong asymmetry with permanent, reduced gains toward the side of lesion. These gain reductions have large variation (gains of 0.26 to 0.83), which may result from preferential sparing of regularly firing afferent fibers following gentamicin ablation. Based on the size and nature of the nonlinearity, an explanation based on Ewald's second law was discounted.

Behavior of eye-movement-related cells in the vestibular nuclei during combined rotational and translational stimuli.

1. Secondary position-vestibular-pause (PVP) neurons in the vestibuloocular reflex (VOR) pathway of adult rhesus monkeys were studied during combined semicircular canal and otolith stimulation. The head was rotated at 0.5 Hz with the axis of rotation centered between the otolith organs (on-axis, ON) and with the axis of rotation 23 cm in front of the otoliths (off-axis, OFF). Both conditions were tested with two different vergence angles by the use of 14-cm (near target, NT) and 100-cm (far target, FT) targets. 2. The tangential translational stimulus to the otoliths in the OFF trials should result in a compensatory eye movement that is opposite in direction to that resulting from the angular stimulus to the canals. The otolith stimulus should be great enough to reverse the eye movement response in the NT OFF trials according to geometric calculations. This reversal in eye movement direction occurred as expected although the latency of the reversal (70 ms) was somewhat greater than expected and the magnitude of the reversal was less than predicted solely on the basis of geometric considerations. 3. The responses of the PVP neurons were corrected for eye position sensitivity to investigate the head movement response components. The amplitude of the response in 22 of 24 PVP cells was reduced in the NT OFF condition compared with the FT OFF condition. This difference was not sufficient in itself to explain the observed reversal in eye movement response. 4. The average sensitivities of the neurons to rotation during the FT and NT ON trials were 1.38 and 1.41 spikes.s-1.deg-1.s-1, respectively. This is too small an increase to account for the increase in the angular VOR gain with near targets (approximately 25%); therefore cells other than PVP neurons must be responsible. 5. The average sensitivities of the PVP neurons to translational accelerations obtained from the FT and NT OFF trials were 305 and 484 spikes.s-1.g-1, respectively, which is higher than most otolith afferent sensitivities reported for 0.5-Hz stimuli in the literature. The otolith component is modified by ocular convergence (59% increase in sensitivity), but this increase is too small to account for the change in the translational VOR gain between the two conditions. 6. Although recordings were only obtained from seven eye-head-velocity cells, the results indicate that these neurons may provide the additional signals not present in the PVP cells. These neurons exhibited large differences between ON and OFF rotations and were found to substantially increase their modulation during the NT conditions compared with that observed during the FT conditions.

Behavior of cells without eye movement sensitivity in the vestibular nuclei during combined rotational and translational stimuli.

A total of 74 neurons that lacked eye movement sensitivity were recorded within the confines of the rostral medial and medial lateral vestibular nuclei. Of these, 36 had response characteristics that were consistent with combined canal and otolith inputs (CAOT neurons), 18 received canal inputs only (CA neurons), and 20 had otolith inputs only (OT neurons). Responses were measured during both rotational and combined rotational and translational stimuli at 0.5 and 3.0 Hz. The otolith signal was found to lag acceleration markedly at both frequencies. Indeed, one subset of CAOT neurons had otolith responses that led translational velocity by only 12 degrees at 0.5 Hz. All translation-responsive neurons decreased their phase lag with respect to acceleration when the stimulus frequency was increased and exhibited a large increase in sensitivity. As these cells have response dynamics that lie between those seen in otolith afferents and those required to drive the motoneurons during the translational VOR, they may represent an intermediate stage in the signal processing.

Eye position signals in the vestibular nuclei: consequences for models of integrator function.

Recordings from neurons in the vestibular nuclei indicate that the cells that carry eye position signals encode the position of a single eye (either ipsilateral or contralateral) during both conjugate and vergence eye movements. The fact that the vestibular nuclei are aware of the positions of each eye is not surprising as the otolith-based linear vestibulo-ocular reflex is known to change its behaviour as a function of uniocular eye position. This result suggests that the signal coming from the oculomotor velocity-to-position integrator specifies the position of each eye during vergence movements and thus must receive a vergence velocity input along with its conjugate velocity inputs. As there is no vergence system in laterally eyed animals, we have proposed two possible models of integrator arrangement that could have developed from conjugate directional (rather than uniocular) integrators in lower animals without frontally mounted eyes. Both of these models explain the existence of near-response cells and produce the required bidirectional gaze paretic nystagmus following unilateral lesions of one integrator. The models also make specific and different predictions concerning the effects of unilateral integrator lesions on the behaviour of the vergence system and thus make suggestions for further experiments.

Eye position signals in the abducens and oculomotor nuclei of monkeys during ocular convergence.

Many neurons in oculomotor pathways encode signals related to eye position. For example, motoneurons in the third, fourth, and sixth cranial nuclei discharge at highly regular rates during fixation intervals. During fixations of far targets, their tonic discharge is linearly related to conjugate eye position. Previous studies provided evidence that premotor cells in brainstem pathways also encoded conjugate eye position. McConville et al. (this volume), however, measured eye movements during binocular fixations when the eyes were converged and concluded that the position signal encoded by premotor position-vestibular-pause (PVP) cells in the vestibular nuclei is related to monocular (right or left) eye position rather than to conjugate eye position. This surprising relationship would not have been noticed in earlier studies that measured the movements of only one eye (using a single eye coil) or that measured only the conjugate movements of the two eyes (using bitemporal EOG electrodes). How general a feature of oculomotor signal processing is this finding? In this paper, we re-examine the eye position signal in abducens and oculomotor neurons when the movements of the two eyes are conjugate and when they are disjunctive and therefore disassociated. The data suggest that abducens neurons (AMNs and AINs) and oculomotor neurons (putative medial rectus motoneurons), unlike PVP cells, are not monocular but encode mixtures of right and left eye position signals.

Interaction of saccadic and vestibular mechanisms in combined eye-head gaze shifts.

Saccades are the only purely volitional eye movements available to primates. They are used extensively to acquire new or interesting targets in the visual environment. Most patients with saccadic disorders are referred to neurologists. Patients complaining of disorientation, however, are often presumed to be suffering from a vestibular disorder. Vestibular and saccadic physiology has been studied mostly in isolation of each other. We examine the interaction of saccadic burst neurons and vestibular signals to achieve accurate gaze shifts.

Combined eye-head gaze shifts in the primate. III. Contributions to the accuracy of gaze saccades.

1. The behavior of the combined eye-head gaze saccade mechanism was investigated in the rhesus monkey under both normal circumstances and in the presence of perturbations delivered to the head by a torque motor. Animals were trained to follow a target light that stepped at regular intervals through an angle of 68 degrees (+/- 34 degrees with respect to the midsagittal plane). Thus all primary saccades were center crossing. On randomly occurring trials the torque motor was pulsed so as to perturb the trajectory of the head, thus allowing us to assess both the functional state of the vestibuloocular reflex (VOR) and the effects of such perturbations on gaze saccade accuracy (gaze is defined as the sum of eye-in-head plus head-in-space, and a gaze saccade as a combined eye-head saccadic gaze shift). 2. Gaze shifts can be divided into two discrete sections: the portion during which the gaze angle is changing (the saccadic portion), and the portion during which the gaze is stationary but the head continues to move (the terminal head-movement portion). For the system to accurately acquire eccentric targets, at least two criteria must be met: 1) the saccadic portion must be accurate, and 2) the compensatory eye movement that occurs during the terminal head-movement portion must be equal and opposite to the head movement, thereby maintaining gaze stability. Perturbations delivered during the terminal head-movement portion of the gaze shift indicated that VOR was functioning normally, and thus we concluded that the compensatory eye movements that accompany head movements were vestibular in origin. 3. As reported previously, during the saccadic portion of large-amplitude gaze saccades, the VOR ceases to function. In spite of this observation, the accuracy of the gaze saccade is not affected by perturbations delivered to the head. Gaze accuracy is maintained both by changing the duration of the saccadic portion and by altering the head trajectory. 4. Because rhesus monkeys often make very rapid head movements (1,200 degrees/s), we wished to discover the velocity range over which the monkey VOR might be expected to operate. Accordingly, in a second series of experiments, VOR function was assessed during passive whole-body rotations with the head fixed. By the use of spring-assisted manual rotations, peak velocities up to 850 degrees/s were achieved. When VOR gain was measured during such rotations, it was found to be equal to 0.9 up to the maximum velocities used.(ABSTRACT TRUNCATED AT 400 WORDS)

On the search for markers of poor vestibular compensation.

The effectiveness of pursuit gain, cancellation of the vestibulo-ocular reflex, and a clinical oscillopsia test were assessed as vestibular function tests and tests that may allow prediction of which patients would compensate poorly after vestibular surgery. Cancellation of the vestibulo-ocular reflex in 17 patients and 17 control subjects was compared. Pursuit gain for 17 patients was determined for three frequencies at peak velocities of 25 and 50 degrees/sec. The oscillopsia test was administered to seven patients during at least the first 6 postoperative months. We are unable to state that any of these parameters were effective "markers" of impaired compensation, but the oscillopsia test appears to be a useful clinical tool for vestibular examination.

Changes in the time constants of the vestibulo-ocular reflex and optokinetic afternystagmus following unilateral ablative vestibular surgery.

Changes in the time constants and gains of the vestibulo-ocular and optokinetic systems were studied in seven patients. Angular acceleration pulse and optokinetic stimuli were administered to three normal subjects and also to seven patients at specific intervals after unilateral ablative vestibular surgery. The gains and the time constants of the two systems were compared. Regression analysis showed that the vestibulo-ocular and optokinetic time constants for slow phase eye movements away from the ablated ear declined significantly after surgery in the patient group, but that the gains did not. A theory based upon variability of system parameters by the CNS is outlined to explain the changes in the dynamics of the two systems after surgery. The data from this study suggest that the time constant may be a useful parameter in clinical vestibular testing.