Motion sickness induced by otolith stimulation is correlated with otolith-induced eye movements.

This article addresses the relationships between motion sickness (MS) and three-dimensional (3D) ocular responses during otolith stimulation. A group of 19 healthy subjects was tested for motion sickness during a 16 min otolith stimulation induced by off-vertical axis rotation (OVAR) (constant velocity 60 degrees /s, frequency 0.16 Hz). For each subject, the MS induced during the session was quantified, and based on this quantification, the subjects were divided into two groups of less susceptible (MS-), and more susceptible (MS+) subjects. The angular eye velocity induced by the otolith stimulation was analyzed in order to identify a possible correlation between susceptibility to MS and 3D eye velocity. The main results show that: (1) MS significantly correlates in a multiple regression with several components of the horizontal vestibular eye movements i.e. positively with the velocity modulation (P<0.01) and bias (P<0.05) of the otolith ocular reflex and negatively with the time constant of the vestibulo-ocular reflex (P<0.01) and (2) the length of the resultant 3D eye velocity vector is significantly larger in the MS+ as compared with the MS- group. Based on these results we suggest that the CNS, including the velocity storage mechanism, reconstructs an eye velocity vector modulated by head position whose length might predict MS occurrence during OVAR.

A model of the cerebellar sensory--motor control applied to fast human forearm movements.

To address the problem of how the cerebellum processes the premotor orders that control fast movements of the forearm, a model of the cerebellar control is proposed: a cybernetic circuit composed of a model of the cerebellar premotor pathways driving a biomechanical model of the human forearm. Experiments consist of recording electromyographic (EMG) activities and cinematic variables of the human forearm during fast, single joint, point-to-point movements performed in horizontal and vertical directions with and without mass. The biomechanical model of the forearm is first validated by comparing actual movements and movements simulated by using, as inputs to this model, the synthesized EMG signals and of real EMG activities recorded during the experiments. Then the entire control model is validated by comparing actual movements to the desired ones simulated by the model of the cerebellar pathways whose inputs are velocity signals with Gaussian time-courses. The results show that approximate inverse functions can be computed by means of inner models of direct functions placed in feedback loops, and suggest that the orientation of any member segment with respect to gravity is computed as a cinematic variable in the Central Nervous System (CNS).

WITHDRAWN: A model of the cerebellar sensory-motor control applied to the fast human forearm movements.

This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause.

Computation of inverse functions in a model of cerebellar and reflex pathways allows to control a mobile mechanical segment.

The command and control of limb movements by the cerebellar and reflex pathways are modeled by means of a circuit whose structure is deduced from functional constraints. One constraint is that fast limb movements must be accurate although they cannot be continuously controlled in closed loop by use of sensory signals. Thus, the pathways which process the motor orders must contain approximate inverse functions of the bio-mechanical functions of the limb and of the muscles. This can be achieved by means of parallel feedback loops, whose pattern turns out to be comparable to the anatomy of the cerebellar pathways. They contain neural networks able to anticipate the motor consequences of the motor orders, modeled by artificial neural networks whose connectivity is similar to that of the cerebellar cortex. These networks learn the direct biomechanical functions of the limbs and muscles by means of a supervised learning process. Teaching signals calculated from motor errors are sent to the learning sites, as, in the cerebellum, complex spikes issued from the inferior olive are conveyed to the Purkinje cells by climbing fibers. Learning rules are deduced by a differential calculation, as classical gradient rules, and they account for the long term depression which takes place in the dendritic arborizations of the Purkinje cells. Another constraint is that reflexes must not impede voluntary movements while remaining at any instant ready to oppose perturbations. Therefore, efferent copies of the motor orders are sent to the interneurones of the reflexes, where they cancel the sensory-motor consequences of the voluntary movements. After learning, the model is able to drive accurately, both in velocity and position, angular movements of a rod actuated by two pneumatic McKibben muscles. Reflexes comparable to the myotatic and tendinous reflexes, and stabilizing reactions comparable to the cerebellar sensory-motor reactions, reduce efficiently the effects of perturbing torques. These results allow to link the behavioral concepts of the equilibrium-point "lambda model" [J Motor Behav 18 (1986) 17] with anatomical and physiological features: gains of reflexes and sensori-motor reactions set the slope of the "invariant characteristic," and efferent copies set the "threshold of the stretch reflex." Thus, mathematical and physical laws account for the raison d'etre of the inhibitory nature of Purkinje cells and for the conspicuous anatomical pattern of the cerebellar pathways. These properties of these pathways allow to perform approximate inverse calculations after learning of direct functions, and insure also the coordination of voluntary and reflex motor orders.

Cerebellar learning of bio-mechanical functions of extra-ocular muscles: modeling by artificial neural networks.

A control circuit is proposed to model the command of saccadic eye movements. Its wiring is deduced from a mathematical constraint, i.e. the necessity, for motor orders processing, to compute an approximate inverse function of the bio-mechanical function of the moving plant, here the bio-mechanics of the eye. This wiring is comparable to the anatomy of the cerebellar pathways. A predicting element, necessary for inversion and thus for movement accuracy, is modeled by an artificial neural network whose structure, deduced from physical constraints expressing the mechanics of the eye, is similar to the cell connectivity of the cerebellar cortex. Its functioning is set by supervised reinforcement learning, according to learning rules aimed at reducing the errors of pointing, and deduced from a differential calculation. After each movement, a teaching signal encoding the pointing error is distributed to various learning sites, as is, in the cerebellum, the signal issued from the inferior olive and conveyed to various cell types by the climbing fibers. Results of simulations lead to predict the existence of a learning site in the glomeruli. After learning, the model is able to accurately simulate saccadic eye movements. It accounts for the function of the cerebellar pathways and for the final integrator of the oculomotor system. The novelty of this model of movement control is that its structure is entirely deduced from mathematical and physical constraints, and is consistent with general anatomy, cell connectivity and functioning of the cerebellar pathways. Even the learning rules can be deduced from calculation, and they reproduce long term depression, the learning process which takes place in the dendritic arborization of the Purkinje cells. This approach, based on the laws of mathematics and physics, appears thus as an efficient way of understanding signal processing in the motor system.

Using sensory weighting to model the influence of canal, otolith and visual cues on spatial orientation and eye movements.

The sensory weighting model is a general model of sensory integration that consists of three processing layers. First, each sensor provides the central nervous system (CNS) with information regarding a specific physical variable. Due to sensor dynamics, this measure is only reliable for the frequency range over which the sensor is accurate. Therefore, we hypothesize that the CNS improves on the reliability of the individual sensor outside this frequency range by using information from other sensors, a process referred to as "frequency completion." Frequency completion uses internal models of sensory dynamics. This "improved" sensory signal is designated as the "sensory estimate" of the physical variable. Second, before being combined, information with different physical meanings is first transformed into a common representation; sensory estimates are converted to intermediate estimates. This conversion uses internal models of body dynamics and physical relationships. Third, several sensory systems may provide information about the same physical variable (e.g., semicircular canals and vision both measure self-rotation). Therefore, we hypothesize that the "central estimate" of a physical variable is computed as a weighted sum of all available intermediate estimates of this physical variable, a process referred to as "multicue weighted averaging." The resulting central estimate is fed back to the first two layers. The sensory weighting model is applied to three-dimensional (3D) visual-vestibular interactions and their associated eye movements and perceptual responses. The model inputs are 3D angular and translational stimuli. The sensory inputs are the 3D sensory signals coming from the semicircular canals, otolith organs, and the visual system. The angular and translational components of visual movement are assumed to be available as separate stimuli measured by the visual system using retinal slip and image deformation. In addition, both tonic ("regular") and phasic ("irregular") otolithic afferents are implemented. Whereas neither tonic nor phasic otolithic afferents distinguish gravity from linear acceleration, the model uses tonic afferents to estimate gravity and phasic afferents to estimate linear acceleration. The model outputs are the internal estimates of physical motion variables and 3D slow-phase eye movements. The model also includes a smooth pursuit module. The model matches eye responses and perceptual effects measured during various motion paradigms in darkness (e.g., centered and eccentric yaw rotation about an earth-vertical axis, yaw rotation about an earth-horizontal axis) and with visual cues (e.g., stabilized visual stimulation or optokinetic stimulation).

A model of the cerebellar pathways applied to the control of a single-joint robot arm actuated by McKibben artificial muscles.

This article describes an expanded version of a previously proposed motor control scheme, based on rules for combining sensory and motor signals within the central nervous system. Classical control elements of the previous cybernetic circuit were replaced by artificial neural network modules having an architecture based on the connectivity of the cerebellar cortex, and whose functioning is regulated by reinforcement learning. The resulting model was then applied to the motion control of a mechanical, single-joint robot arm actuated by two McKibben artificial muscles. Various biologically plausible learning schemes were studied using both simulations and experiments. After learning, the model was able to accurately pilot the movements of the robot arm, both in velocity and position.

Motion sickness susceptibility correlates with otolith- and canal-ocular reflexes.

Since motion sickness (MS) never occurs in individuals who lack functional vestibular apparatus, it has been suggested that MS susceptible individuals have more sensitive vestibular systems than non-susceptible people. However, previous investigations involving only stimulation of the semi-circular canals have been inconclusive. We measured gain and time constant (TC) of horizontal canal-ocular reflex (COR) and magnitude of otolith-ocular reflex (OOR). We found that MS susceptibility was not correlated to COR gain but was negatively correlated to OOR magnitude. Thus, MS susceptible individuals do not have more sensitive vestibular systems. We also found a positive correlation between MS susceptibility and TC. We hypothesize that central vestibular integration (velocity storage mechanism), by increasing low frequency vestibular inputs, would favour MS.

Unilateral vestibular neuritis with otolithic signs and off-vertical axis rotation.

Off-vertical axis rotation (OVAR) at constant velocity is a dynamic otolith stimulus that induces horizontal and vertical eye movement responses. To determine the value of this examination as a test for unilateral otolithic hypofunction, we compared the OVAR responses of patients suffering from acute vestibular neuritis (VN) without any sign of otolith affection, with those of patients suffering from acute VN with otolithic signs. The horizontal eye movement bias component shows directional preponderance (DP) significantly higher in patients with otolithic signs than in patients not presenting them. However, as bias DP also reflects the imbalance between right and left horizontal canals activity, this greater bias DP could be explained by the more severe canals impairment-evaluated by caloric test-found in patients with otolithic signs. No significant difference can be shown on horizontal modulation. The DP of vertical modulation is significantly higher in patients presenting otolithic signs than in patients not presenting them: in the case of otolithic signs, the responses are smaller during rotations toward the affected side. Therefore, this variable could be used as an indication of unilateral otolithic hypofunction.

Computation of inverse dynamics for the control of movements.

Accuracy of movements requires that the central nervous system computes approximate inverse functions of the mechanical functions of limb articulations. In vertebrates, this is known to be achieved within the cerebellar pathways, and also in the cerebral cortex of primates. A cybernetic circuit achieving this computation allows accurate simulation of fast movements of the eye or forearm. It is consistent with anatomy, and with the classical view of the cerebellum as permanently supervised by the inferior olive. The inferior olive detects over-or under-shoots of movements, and the resulting climbing fiber activity corrects ongoing movements, regulates the function of cerebellar cortex and nuclei, and sets the gains of the sensorimotor reactions.

Unilateral peripheral semicircular canal lesion and off-vertical axis rotation.

Off vertical axis rotation (OVAR) is a stimulus that can be used to assess the otolith-ocular reflex. However, experimental data suggest that isolated unilateral lesion of the lateral semicircular canal (SCC) nerve could modify responses to OVAR. Thus, to determine what nystagmus variables are not affected by SCC dysfunction and might be used as indices of otolithic disease, responses to OVAR were compared in 39 healthy controls and in 19 patients suffering from acute unilateral vestibular neuritis (VN), without any sign of otolith dysfunction. Horizontal and vertical slow phase velocities (SPV) were measured during earth vertical axis rotation (EVAR), and during OVAR at a tilt angle of 9 degrees and rotation velocity of 60 degrees/s. During OVAR, horizontal SPV consists of a sinusoidal modulation superimposed on a sustained bias opposite to the rotation. Vertical SPV consists of a sinusoidal modulation without bias. In patients, the bias shows directional preponderance (DP) toward the healthy side, strongly correlated to EVAR nystagmus DP. It would therefore simply reflect an imbalance, produced by the unilateral peripheral vestibular lesion, between right and left vestibular nuclei activity. On the other hand, vertical and horizontal modulations are not significantly different in patients and controls. Since the cause and the site of VN are not known, we cannot be sure that patients had pure SCC deafferentation. However, as all of them had SCC paresis it is concluded that OVAR modulations are not affected by a strong dysfunction of the pathways issued from the SCCs.

Motion sickness during off-vertical axis rotation: prediction by a model of sensory interactions and correlation with other forms of motion sickness.

Motion sickness (MS) susceptibility of 108 normal subjects was measured during off-vertical axis rotation (OVAR) as a function of angular velocity (60-180 degrees/s). The chair rotated about a longitudinal axis tilted 30 degrees with respect to gravity. For each velocity, we measured the duration of exposure necessary to evoke a moderate malaise, with a limit of 30 min. MS appeared the fastest at a rotation velocity of 105 degrees/s; higher or lower velocities were less provocative. These results are in good agreement with predictions made by Zupan et al. [in ICANN'94, Springer-Verlag, 1995] by means of a MS mathematical model derived from a model of sensory interactions [Droulez and Darlot, in Attention and Performance, Vol. 13, Lawrence Erlbaum, Hillsdale, 1989]. We also found that MS susceptibility during OVAR is positively correlated with susceptibility to other forms of MS. Since OVAR induces sensory messages very different from those induced by other provocative stimulations, this could suggest that the sensitivity of a common final vegetative locus is an important factor of the individual differences in susceptibility to MS.

Eye movements and motion perception induced by off-vertical axis rotation (OVAR) at small angles of tilt after spaceflight.

The nystagmus and motion perception of two astronauts were recorded during Earth-vertical axis rotation and during off-vertical axis rotation (OVAR) before and after 7 days of spaceflight. Postflight, the peak velocity and duration of per- and postrotatory nystagmus during velocity steps about the Earth-vertical axis were the same as preflight values. During OVAR at constant velocity (45/s, tilt angles successively 5, 10, and 15 degrees), the mean horizontal slow-phase eye velocity (bias), produced by the 'velocity storage mechanism' in the vestibular system, and the peak-to-peak amplitude (modulation) in horizontal eye velocity and position, generated from the output of otolith afferents, were also the same before as after flight. There were, however, changes in the vertical eve position and in the perceived body motion during OVAR. The angle of the perceived body path described as a cone was larger in both astronauts postflight. One astronaut experienced either a large cone angle with its axis upright, or a smaller cone angle with its axis tilted backwards, accompanied by an upward vertical eye drift. These results suggest an increase in the sensitivity of the otolithic system after spaceflight and a longer period of readaptation to Earth's gravity for otolith-induced responses than for canal-induced responses. Our data support the hypothesis that just after spaceflight the CNS generally interprets changes in the otolith signals to be due to translation rather than to tilt.

The cerebellum as a predictor of neural messages--II. Role in motor control and motion sickness.

The hypothesis of a "stable estimator" was proposed in the preceding article as a circuit computing an internal estimate of a body movement variable and endowed with regulating properties. Such a circuit would exist for each variable, and would be embedded in a particular folium of the cerebellar cortex and the related paths of the brainstem nuclei and the inferior olive. In this article, the action of the premotor orders on the stable estimator circuit is studied, at initiation and during execution of voluntary movements. A feedback loop via the cerebellar cortex would control on-going movements and maintain the efficacy of the stabilizing sensorimotor reaction, while preventing its interfering with the movement. The regulating loop via the inferior olive would have a short-term role in initiating movements and would boost insufficient stabilizing reactions. The discrepancy between internal estimates of the same variable would be reflected in motion sickness.

The cerebellum as a predictor of neural messages--I. The stable estimator hypothesis.

To describe how the central nervous system combines sensory messages, the hypothesis of a "stable estimator" is proposed: the central nervous system would construct internal estimates of the physical variables characterizing the body movements (e.g. head rotational velocity in space), while a regulating circuit would optimize the process of estimation of each variable, according to the available information and the overall performances of the sensorimotor reactions. The stable estimator of each variable would be embedded in a definite folium of the cerebellar cortex and the related cerebellar and brainstem nuclei. It would be controlled by the related part of the inferior olive. The estimate of each physical variable would be constructed by complementing the message from a dedicated sensory system (e.g. the semi-circular canals, which measure head rotational velocity in space) by neural messages related to the same variable (e.g. eye velocity in the head and retinal slip). Thus, the estimate would be accurate over the widest possible physiological ranges of frequency and velocity. The complementing signals would result from combining estimates of other variables (such as gaze velocity and eye velocity in the orbit), according to rules reproducing the relationships between physical variables. From the same complementing signals, the message from the dedicated sensory system would be predicted, and it is argued that this predictive function resides in the cerebellar cortex. The inferior olive would compare an actual signal about the performance of a sensorimotor reaction to signals of expected performance, computed from the various internal estimates of the variables which determine this performance. Any erroneous setting in a stable estimator would cause differences between the actual and the expected values. Then the inferior olive would compute an error signal directing compensatory functional plasticity. Finally, the whole estimating circuit would be regulated so that the internal coherence between neural messages and the performance of sensorimotor reactions would be achieved. Anatomical identifications and rules of functional plasticity are proposed.

Motion perceptions induced by off-vertical axis rotation (OVAR) at small angles of tilt.

Off-vertical axis rotation in darkness induces a perception of body motion which lasts as long as rotation continues. Perceived body motion is the combination of two simultaneous displacements. The most easily perceived is a translation without rotation along a conical path, at the frequency of the actual rotation. Meanwhile, the subjects feel as if they were always facing towards the same direction. The summit of the cone is generally below the head, from the waist to below the feet, and subjects have a sense of progression in the direction opposite to actual spinning. Some subjects feel, on the contrary, the summit of the cone above their heads, and the progression in the direction of spinning. Subjects also perceived another body motion, although it was faint for some of them. It consists of a rotation at low velocity in the same direction as progression along the cone. The axis of the cone is perceived as slowly rotating along a larger cone. These motion perceptions increase with tilt angle and rotation velocity. They probably result from the analysis by the Central Nervous System of the acceleration acting on the otoliths. The perceived trajectory would be reconstructed from estimates of gravity, and kinematic variables such as head translational acceleration and velocity, and head rotational velocity. The same variables would account for OVAR-induced nystagmus. Motion sickness would result from the impossibility of reconstructing a consistent body movement from most sets of values of these variables.

Nystagmus induced by off-vertical rotation axis in the cat.

1) In the alert cat, nystagmus induced by off-vertical axis rotation (OVAR) was recorded following steps in head velocity or ramps of velocity at constant acceleration below canal threshold. Dependence of nystagmus characteristics on tilt angle of rotation axis and head velocity was studied. Similar results were obtained with both types of stimulation. 2) Mean and modulation amplitude of horizontal eye velocity increased with tilt angle in the range 0-30 degrees. 3) Both variables increased also with head velocity, but with different trends, probably because they are set by different mechanisms. When head rotational velocity was increased above 80 degrees/s, mean eye velocity progressively decreased to zero. 4) In spite of variations from one animal to another, some regularity was observed in the phase of eye velocity modulation. In several cases, a reduction in phase lead of eye velocity with respect to conventional origin of phases (nose-down position) was observed when head velocity increased. 5) Time constant of post-OVAR nystagmus decreased with the tilt angle of the rotation axis from gravity, but not with the orientation of the head with respect to rotation axis. 6) The results could be accounted for by a general equation describing the vestibulo-ocular reflex, provided that estimates of kinematic variables of head movement (head rotational and translational velocities), and visual target distance could be computed by the Central Nervous System.

Eye movements induced by off-vertical axis rotation (OVAR) at small angles of tilt.

Off-vertical rotation (OVAR) in darkness induced continuous horizontal nystagmus in humans at small tilts of the rotation axis (5 to 30 degrees). The horizontal slow eye velocity had two components: a mean velocity in the direction opposite to head rotation and a sinusoidal modulation around the mean. Mean velocity generally did not exceed 10 deg/s, and was less than or equal to the maximum velocity of optokinetic after-nystagmus (OKAN). Both the mean and modulation components of horizontal nystagmus increased with tilt angle and rotational velocity. Vertical slow eye velocity was also modulated sinusoidally, generally around zero. The amplitude of the vertical modulation increased with tilt angle, but not with rotational velocity. In addition to modulations in eye velocity, there were also modulations in horizontal and vertical eye positions. These would partially compensate for head position changes in the yaw and pitch planes during each cycle of OVAR. Modulations in vertical eye position were regular, increased with increases in tilt angle and were separated from eye velocity by 90 deg. These results are compatible with the interpretation that, during OVAR, mean slow velocity of horizontal nystagmus is produced by the velocity storage mechanism in the vestibular system. In addition, they indicate that the otolith organs induce compensatory eye position changes with regard to gravity for tilts in the pitch, yaw and probably also the roll planes. Such compensatory changes could be utilized to study the function of the otolith organs. A functional interpretation of these results is that nystagmus attempts to stabilize the image on the retina of one point of the surrounding world. Mean horizontal velocity would then be opposite to the estimate of head rotational velocity provided by the output of the velocity storage mechanism, as charged by an otolithic input during OVAR. In spite of the lack of actual translation, an estimate of head translational velocity could, in this condition, be constructed from the otolithic signal. The modulation in horizontal eye position would then be compensatory for the perceived head translation. Modulation of vertical eye velocity would compensate for actual changes in head orientation with respect to gravity.

Modulation by eye position of neck muscle contraction evoked by electrical labyrinthine stimulation in the alert cat.

Modulation of vestibulo-spinal reflexes by gaze is a model system for studying interactions between voluntary and reflex motor activity. In the alert cat, the EMG of Splenius and Obliquus capitis muscles increases with ipsilateral gaze eccentricity during spontaneous eye movements. Labyrinth stimulation by current pulses evokes EMGs with latencies consistent with a three neuron vestibulocollic pathway. The amplitude of evoked activity increases with eye position. The directions in which eye movements increase EMG was usually the same for both spontaneous and induced EMG activity, namely, horizontal and ipsilateral. However, sometimes the increase in spontaneous EMG occurred with horizontal eye position, whereas the induced EMG changed with vertical eye position. Spontaneous and evoked EMG are then modulated by different eye position signals. Command signals reflecting eye position probably reach two different types of neurons in the vestibulo-collic pathway, most likely secondary vestibular neurons and neck muscle motoneurons.