Mark F. Walker

Directional Abnormalities of Vestibular and Optokinetic Responses in Cerebellar Disease

Abstract: Directional abnormalities of vestibular and optokinetic responses in patients with cerebellar degeneration are reported. Three‐axis magnetic search‐coil recordings of the eye and head were performed in eight cerebellar patients. Among these patients, examples of directional cross‐coupling were found during (1) high‐frequency, high‐acceleration head thrusts; (2) constant‐velocity chair rotations with the head fixed; (3) constant‐velocity optokinetic stimulation; and (4) following repetitive head shaking. Cross‐coupling during horizontal head thrusts consisted of an inappropriate upward eye‐velocity component. In some patients, sustained constant‐velocity yaw‐axis chair rotations produced a mixed horizontal‐torsional nystagmus and/or an increase in the baseline vertical slow‐phase velocity. Following horizontal head shaking, some patients showed an increase in the slow‐phase velocity of their downbeat nystagmus. These various forms of cross‐coupling did not necessarily occur to the same degree in a given patient; this suggests that different mechanisms may be responsible. It is suggested that cross‐coupling during head thrusts may reflect a loss of calibration of brainstem connections involved in the direct vestibular pathways, perhaps due to dysfunction of the flocculus. Cross‐coupling during constant‐velocity rotations and following head shaking may result from a misorientation of the angular eye‐velocity vector in the velocity‐storage system. Finally, responses to horizontal optokinetic stimulation included an inappropriate torsional component in some patients. This suggests that the underlying organization of horizontal optokinetic tracking is in labyrinthine coordinates. The findings are also consistent with prior animal‐lesion studies that have shown a role for the vestibulocerebellum in the control of the direction of the VOR.

Why do patients with PSP fall? Evidence for abnormal otolith responses

Background: Patients with progressive supranuclear palsy (PSP) fall frequently, beginning early in the course of their disease. Abnormal vestibulospinal reflexes are suspected, but the angular vestibulo-ocular reflex, which is mediated by the labyrinthine semicircular canals, survives late into the course of the disease. Objective: To test the hypothesis that otolithic-mediated reflexes are abnormal in PSP. Methods: We tested otolith-ocular reflexes (the translational vestibulo-ocular reflex [tVOR]) during combined rotation-translation in nine patients with PSP and nine age-matched control subjects; subjects viewed far and near targets. We also tested click-induced otolith-spinal reflexes (vestibular-evoked myogenic potentials [VEMPs]) in 10 patients with PSP and 30 age-matched controls. Results: All patients with PSP had small tVOR responses during near viewing that were, on average, only 12% of those of control subjects (p = 0.001). Patients with PSP also showed a reduction of the amplitude of VEMPs compared to control subjects (median [range]: 54.3 [16.8 to 214] vs 149 [11.6 to 466], p = 0.001). Conclusions: Taken together, these results indicate that abnormal otolith-mediated reflexes may be at least partly responsible for frequent falls in progressive supranuclear palsy, and deserve further study.

Eye-position dependence of torsional velocity during interaural translation, horizontal pursuit, and yaw-axis rotation in humans

The translational vestibulo-ocular reflex (tVOR) stabilizes an image on the fovea during linear movements of the head. It has been suggested that the tVOR may share pathways with the pursuit system. We asked whether the tVOR and pursuit would be similar in their behavior relative to Listings Law. We compared torsional eye velocity as a function of vertical orbital position during interaural translation, pursuit, and yaw-axis rotation. We found that the eye-position-dependence of torsion was similar during translation and pursuit, which differed from that during yaw-axis rotation. These findings further support a close relationship between the mechanisms that generate pursuit and the tVOR.

The effect of hyperventilation on downbeat nystagmus in cerebellar disorders.

Hyperventilation can affect nystagmus in patients with vestibular disorders. However, the effects on nystagmus in patients with cerebellar disease have not been systematically studied. Using the magnetic field search coil technique, we studied the effects of hyperventilation on nystagmus in a series of cerebellar patients. In four of eight patients, hyperventilation produced an increase in the slow-phase velocity of downbeat nystagmus. We speculate that this effect may be mediated through metabolic effects on cerebellar calcium channels.

BEDSIDE VESTIBULAR EXAMINATION

A careful neuro-otologic examination is important in the diagnosis of vestibular disorders. This article reviews the bedside examination, beginning with the underlying physiologic principles. Techniques for testing static and dynamic vestibulo-ocular and vestibulospinal function are summarized. Finally, the use of specific provocative maneuvers is described.

The Cerebellar Contribution to Eye Movements Based upon Lesions

Abstract: The study of human cerebellar patients and monkeys with experimental cerebellar lesions has taught us much about the role of the cerebellum in normal ocular motor control. Here we emphasize recent findings that point to a role for the cerebellum in (1) the control of the three‐dimensional axis about which the eye rotates in response to visual and vestibular stimuli, and (2) the generation of the translational VOR. Findings in cerebellar patients include abnormalities of eye torsion during attempted fixation that suggest a cerebellar role in the control of torsion so that Listings law is obeyed. Abnormal torsion during vertical pursuit suggests that central processing of information for smooth pursuit may be based upon a phylogenetically old, semicircular canal coordinate scheme. Inappropriate and disconjugate vertical and torsional eye movements (“cross‐coupling”) occur during brief, high‐acceleration rotations of the head. This suggests a role for the cerebellum in the binocular control of the rotation axis of the VOR. Finally, abnormalities of the modulation of the translational VOR with near viewing in cerebellar patients, but with sparing of the very initial 25‐30 msec of response, suggests an important role for the cerebellum in the translational VOR.

Short‐Term Adaptation of the VOR: Non‐Retinal‐Slip Error Signals and Saccade Substitution

We studied short‐term (30 min) adaptation of the vestibulo‐ocular reflex (VOR) in five normal humans using a “position error” stimulus without retinal image motion. Both before and after adaptation a velocity gain (peak slow‐phase eye velocity/peak head velocity) and a position gain (total eye movement during chair rotation/amplitude of chair motion) were measured in darkness using search coils. The vestibular stimulus was a brief (~700 ms), 15° chair rotation in darkness (peak velocity 43°/s). To elicit adaptation, a straight‐ahead fixation target disappeared during chair movement and when the chair stopped the target reappeared at a new location in front of the subject for gain‐decrease (×0) adaptation, or 10° opposite to chair motion for gain‐increase (×1.67) adaptation. This position‐error stimulus was effective at inducing VOR adaptation, though for gain‐increase adaptation the primary strategy was to substitute augmenting saccades during rotation while for gain‐decrease adaptation both corrective saccades and a decrease in slow‐phase velocity occurred. Finally, the presence of the position‐error signal alone, at the end of head rotation, without any attempt to fix upon it, was not sufficient to induce adaptation. Adaptation did occur, however, if the subject did make a saccade to the target after head rotation, or even if the subject paid attention to the new location of the target without actually looking at it.

Lesions of the Cerebellar Nodulus and Uvula in Monkeys: Effect on Otolith-Ocular Reflexes

We studied two rhesus monkeys before and after surgical ablation of the nodulus and uvula (Nod/Uv) of the cerebellum. Three-axis eye movements were recorded with the magnetic-field scleral search coil system during a variety of vestibular and ocular motor tasks. Here we describe the effects of the Nod/Uv lesions on dynamic (head translation) and static (head tilt) otolith-mediated vestibulo-ocular reflexes. The main findings were: 1. eye velocity during sinusoidal vertical translation (1.5 Hz) was reduced by 59% in the dark and 36% in the light; 2. eye velocity during steps of horizontal translation was reduced, but only in the dark and more so during the sustained (constant velocity) than the initial (acceleration) part of the response, and 3. there was a torsional nystagmus that depended on the position of roll head tilt, but static ocular counterroll was unchanged. These results suggest new roles for the Nod/Uv in the processing of otolith signals. This is likely important not only for facilitating gaze during linear head motion, but also for maintaining postural stability and ones orientation relative to gravity. The lesions appeared to have a greater effect on responses to vertical motion, particularly in the light (in contrast, responses to interaural translation in the light were nearly normal), suggesting a particular importance of the Nod/Uv in processing signals arising from the sacculi.

Rotational and translational optokinetic nystagmus have different kinematics

We studied the dependence of ocular torsion on eye position during horizontal optokinetic nystagmus (OKN) elicited by random-dot translational motion (tOKN) and prolonged rotation in the light (rOKN). For slow and quick phases, we fit the eye-velocity axis to vertical eye position to determine the tilt angle slope (TAS). The TAS for tOKN was 0.48 for both slow and quick phases, close to what is found during translational motion of the head. The TAS for rOKN was less for both slow (0.11) and quick phases (0.26), close to what is found during rotational motion of the head. Our findings are consistent with the notion that translational and rotational optic flow are processed differently by the brain and that they produce different 3-D eye movement commands that are comparable to the different commands generated in response to vestibular signals when the head is actually translating or rotating.

Eye-position dependence of torsional velocity during step-ramp pursuit and transient yaw rotation in humans

The time course of eye-position-dependent torsion during transient horizontal pursuit and yaw rotation was examined in seven normal human subjects. The stimuli consisted of step-ramp target motion (25, 40°/s) and brief chair rotation (~200°/s2 accelerated to 40°/s) at three different vertical positions (center 0°, up or down 15°). Three-dimensional eye movements were recorded with dual search coils. The kinematics of pursuit and the rotational vestibulo-ocular reflex (rVOR) were assessed by determining the tilt-angle slope, a measure of the variation of the axis of eye-velocity with vertical eye position. We found that the tilt-angle slope during pursuit was initially 0.4±0.07 (mean±95% confidence interval) and then gradually rose to 0.64±0.04, at about the time that the steady-state eye-velocity was reached. The rVOR began with a nearly head-fixed axis (0.08±0.04), appropriate for full retinal image stabilization, followed by a gradual increase of the tilt-angle slope to 0.31±0.02. Thus, differences between pursuit and the rVOR with respect to Listing’s law can be seen from the onset of transient responses, although in both cases eye-position-dependent torsion increases with time. This temporal evolution of the axis of eye-velocity may involve the velocity-storage mechanism.