Tilting the head in roll to or from the upright while rotating at a constant velocity (roll while rotating, RWR) alters the position of the semicircular canals relative to the axis of rotation. This produces vertical and horizontal nystagmus, disorientation, vertigo, and nausea. With recurrent exposure, subjects habituate and can make more head movements before experiencing overpowering motion sickness. We questioned whether promethazine lessened the vertigo or delayed the habituation, whether habituation of the vertigo was related to the central vestibular time constant, i.e., to the time constant of velocity storage, and whether the severity of the motion sickness was related to deviation of the axis of eye velocity from gravity. Sixteen subjects received promethazine and placebo in a double-blind, crossover study in two consecutive 4-day test series 1 month apart, termed series I and II. Horizontal and vertical eye movements were recorded with video-oculography while subjects performed roll head movements of approx. 45 degrees over 2 s to and from the upright position while being rotated at 138 degrees /s around a vertical axis. Motion sickness was scaled from 1 (no sickness) to an endpoint of 20, at which time the subject was too sick to continue or was about to vomit. Habituation was determined by the number of head movements that subjects made before reaching the maximum motion sickness score of 20. Head movements increased steadily in each session with repeated testing, and there was no difference between the number of head movements made by the promethazine and placebo groups. Horizontal and vertical angular vestibulo-ocular reflex (aVOR) time constants declined in each test, with the declines being closely correlated to the increase in the number of head movements. The strength of vertiginous sensation was associated with the amount of deviation of the axis of eye velocity from gravity; the larger the deviation of the eye velocity axis from gravity, the more severe the motion sickness. Thus, promethazine neither reduced the nausea associated with RWR, nor retarded or hastened habituation. The inverse relationship between the aVOR time constants and number of head movements to motion sickness, and the association of the severity of motion sickness with the extent, strength, and time of deviation of eye velocity from gravity supports the postulate that the spatiotemporal properties of velocity storage, which are processed between the nodulus and uvula of the vestibulocerebellum and the vestibular nuclei, are likely to represent the source of the conflict responsible for producing motion sickness.

The foot is a critical interface between the body and supporting surface during walking, but there is no coherent framework on which to model the dynamics of the stance and swing phases. To establish this framework, we studied the rotational and translational dynamics of foot movement in three dimensions with a motion detection system (OPTOTRAK), while subjects walked on a treadmill. Positions, velocities, and durations were normalized to leg-length and gravity. Foot position and rotation at toe-off were closely related to walking velocity. Foot pitch at toe clearance increased with walking velocity, but the medial-lateral and vertical toe positions were unaltered. Phase-plane trajectories along the fore-aft direction, i.e., plots of toe velocity versus position, were circular during the swing phases, with radii proportional to walking velocity. Peak forward, lateral, and upward velocities were linearly related to corresponding excursions, forming main sequences. A second order model predicted the changes in toe position and velocity, and the approximately hyperbolic decrements in duration as a function of walking velocity. The model indicates that the foot is controlled in an overdamped manner during the stance phase and as a feedback-controlled undamped pendulum during the swing. The data and model suggest that the state of the foot at toe-off, set by walking velocity during the stance phase, determines the dynamics of the swing phase. Thus, in addition to determining locomotion kinematics, walking velocity plays a critical role in determining the phase-plane trajectories and main sequence relationships of foot movements during the swing phases.

Nystagmus induced by off-vertical axis rotation (OVAR) about a head yaw axis is composed of a yaw bias velocity and modulations in eye position and velocity as the head changes orientation relative to gravity. The bias velocity is dependent on the tilt of the rotational axis relative to gravity and angular head velocity. For axis tilts <15 degrees, bias velocities increased monotonically with increases in the magnitude of the projected gravity vector onto the horizontal plane of the head. For tilts of 15-90 degrees, bias velocity was independent of tilt angle, increasing linearly as a function of head velocity with gains of 0.7-0.8, up to the saturation level of velocity storage. Asymmetries in OVAR bias velocity and asymmetries in the dominant time constant of the angular vestibuloocular reflex (aVOR) covaried and both were reduced by administration of baclofen, a GABA(B) agonist. Modulations in pitch and roll eye positions were in phase with nose-down and side-down head positions, respectively. Changes in roll eye position were produced mainly by slow movements, whereas vertical eye position changes were characterized by slow eye movements and saccades. Oscillations in vertical and roll eye velocities led their respective position changes by approximately 90 degrees, close to an ideal differentiation, suggesting that these modulations were due to activation of the orienting component of the linear vestibuloocular reflex (lVOR). The beating field of the horizontal nystagmus shifted the eyes 6.3 degrees /g toward gravity in side down position, similar to the deviations observed during static roll tilt (7.0 degrees /g). This demonstrates that the eyes also orient to gravity in yaw. Phases of horizontal eye velocity clustered ~180 degrees relative to the modulation in beating field and were not simply differentiations of changes in eye position. Contributions of orientating and compensatory components of the lVOR to the modulation of eye position and velocity were modeled using three components: a novel direct otolith-oculomotor orientation, orientation-based velocity modulation, and changes in velocity storage time constants with head position re gravity. Time constants were obtained from optokinetic after-nystagmus, a direct representation of velocity storage. When the orienting lVOR was combined with models of the compensatory lVOR and velocity estimator from sequential otolith activation to generate the bias component, the model accurately predicted eye position and velocity in three dimensions. These data support the postulates that OVAR generates compensatory eye velocity through activation of velocity storage and that oscillatory components arise predominantly through lVOR orientation mechanisms.

We tested the hypothesis that motion sickness is produced by an integration of the disparity between eye velocity and the yaw-axis orientation vector of velocity storage. Disparity was defined as the magnitude of the cross product between these two vectors. OVAR, which is known to produce motion sickness, generates horizontal eye velocity with a bias level related to velocity storage, as well as cyclic modulations due to re-orientation of the head re gravity. On average, the orientation vector is close to the spatial vertical. Thus, disparity can be related to the bias and tilt angle. Motion sickness sensitivity was defined as a ratio of maximum motion sickness score to the number of revolutions, allowing disparity and motion sickness sensitivity to be correlated. Nine subjects were rotated around axes tilted 10°–30° from the spatial vertical at 30°/s–120°/s. Motion sickness sensitivity increased monotonically with increases in the disparity due to changes in rotational velocity and tilt angle. Maximal motion sickness sensitivity and bias (6.8°/s) occurred when rotating at 60°/s about an axis tilted 30° Modulations in eye velocity during OVAR were unrelated to motion sickness sensitivity. The data were predicted by a model incorporating an estimate of head velocity from otolith activation, which activated velocity storage, followed by an orientation disparity comparator that activated a motion sickness integrator. These results suggest that the sensory-motor conflict that produces motion sickness involves coding of the spatial vertical by the otolith organs and body tilt receptors and processing of eye velocity through velocity storage.