Biomedical subjects

Theodore Raphan

Publications and source records attributed to Theodore Raphan.

30 records · Page 2Linked to original sources

PubMed2004

Gravity-dependent and gravity-independent gain changes during vertical vestibulo-ocular reflex (VOR) adaptation.

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively increased or decreased with monkeys in a side down position, and the gains were tested with the axis of rotation tilted in 10 degrees increments from left- to right-side-down. Gain changes, expressed as a percentage of the preadapted values, were plotted as a function of head tilt, and fit with a cosine function. The amplitude of the cosine was half of the gravity-dependent component of the gain change and the bias, the gravity independent component. The largest changes in the gain of both components occurred in the first 30 min and continued at a slower rate throughout adaptation. The gravity-dependent and -independent gain changes were larger for gain decreases than for gain increases, but both components had similar dynamics. We conclude that the alteration in gain of the aVOR always occurs in the context of gravity.

Adaptation, Physiological↗

PubMed2003

The relation of motion sickness to the spatial-temporal properties of velocity storage.

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.

Adult↗

PubMed2003

Gravity-specific adaptation of the angular vestibuloocular reflex: dependence on head orientation with regard to gravity.

The gain of the vertical angular vestibuloocular reflex (aVOR) was adaptively altered by visual-vestibular mismatch during rotation about an interaural axis, using steps of velocity in three head orientations: upright, left-side down, and right-side down. Gains were decreased by rotating the animal and visual surround in the same direction and increased by visual and surround rotation in opposite directions. Gains were adapted in one head position (single-state adaptation) or decreased with one side down and increased with the other side down (dual-state adaptation). Animals were tested in darkness using sinusoidal rotation at 0.5 Hz about an interaural axis that was tilted from horizontal to vertical. They were also sinusoidally oscillated from 0.5 to 4 Hz about a spatial vertical axis in static tilt positions from yaw to pitch. After both single- and dual-state adaptation, gain changes were maximal when the monkeys were in the position in which the gain had been adapted, and the gain changes progressively declined as the head was tilted away from that position. We call this gravity-specific aVOR gain adaptation. The spatial distribution of the specific aVOR gain changes could be represented by a cosine function that was superimposed on a bias level, which we called gravity-independent gain adaptation. Maximal gravity-specific gain changes were produced by 2-4 h of adaptation for both single- and dual-state adaptations, and changes in gain were similar at all test frequencies. When adapted while upright, the magnitude and distribution of the gravity-specific adaptation was comparable to that when animals were adapted in side-down positions. Single-state adaptation also produced gain changes that were independent of head position re gravity particularly in association with gain reduction. There was no bias after dual-state adaptation. With this difference, fits to data obtained by altering the gain in separate sessions predicted the modulations in gain obtained from dual-state adaptations. These data show that the vertical aVOR gain changes dependent on head position with regard to gravity are continuous functions of head tilt, whose spatial phase depends on the position in which the gain was adapted. From their different characteristics, it is likely that gravity-specific and gravity-independent adaptive changes in gain are produced by separate neural processes. These data demonstrate that head orientation to gravity plays an important role in both orienting and tuning the gain of the vertical aVOR.

Adaptation, Physiological↗

PubMed2003

The critical role of velocity storage in production of motion sickness.

We propose that motion sickness is mediated through the orientation properties of velocity storage in the vestibular system that tend to align eye velocity produced by the angular vestibulo-ocular reflex (aVOR) with gravito-inertial acceleration (GIA). (GIA is the sum of the linear accelerations acting on the head. In the absence of translational accelerations, gravity is the GIA.) We further postulate that motion sickness produced by cross-coupled vestibular stimulation can be characterized by a metric composed of the disparity between the axis of eye rotation and the GIA, the strength of the response to angular motion, and the response duration, as determined by the central vestibular time constant, that is, by the time constant of velocity storage. The nodulus and uvula of the vestibulocerebellum are likely to be the central sites where the disparity is sensed, where the vestibular time constants are habituated, and where links are made to the autonomic system to produce the symptoms and signs.

Adult↗

PubMed2003

Adaptive changes in the angular VOR: duration of gain changes and lack of effect of nodulo-uvulectomy.

Alterations in the gain of the vertical angular vestibulo-ocular reflex (VOR) are dependent on the head position in which the gain changes were produced. We determined how long gravity-dependent gain changes last in monkeys after four hours of adaptation, and whether the adaptation is mediated through the nodulus and uvula of the vestibulocerebellum. Vertical VOR gains were adaptively modified by rotation about an interaural axis, in phase or out of phase with the visual surround. Vertical VOR gains were modified with the animals in one of three orientations: upright, left-side down, or right-side down. Monkeys were tested in darkness for up to four days after adaptation using sinusoidal rotation about an interaural axis that was incrementally tilted in 10 degrees steps from vertical to side down positions. Animals were unrestrained in their cages in normal light conditions between tests. Gravity-dependent gain changes lasted for a day or less after adaptation while upright, but persisted for two days or more after on-side adaptation. These data show that gravity-dependent gain changes can last for prolonged periods after only four hours of adaptation in monkeys, as in humans. They also demonstrate that natural head movements made while upright do not provide an adequate stimulus for rapid recovery of vertical VOR gains that were induced on side. In two animals, the nodulus and uvula were surgically ablated. Vertical gravity-dependent gain changes were not significantly different before and after surgery, indicating that the nodulus and uvula do not have a critical role in producing them.

Adaptation, Physiological↗

PubMed2003

Ocular and perceptual responses to linear acceleration in microgravity: alterations in otolith function on the COSMOS and Neurolab flights.

In this paper we review space flight experiments performed by our laboratory. Rhesus monkeys were tested before and after 12 days in orbit on COSMOS flights 2044 (1989) and 2229 (1992-1993). There was a long-lasting decrease in post-flight ocular counter-rolling (70%) and vergence (50%) during off-vertical axis rotation. In one animal, the orientation of optokinetic after-nystagmus shifted by 28 degrees from the spatial vertical towards the body vertical early post-flight. Otolith-ocular and perceptual responses were also studied in four astronauts on the 17-day Neurolab shuttle mission (STS-90) in 1998. Ocular counter-rolling was unchanged in response to 1-g and 0.5-g Gy centrifugation during and after flight and to post-flight static roll tilts relative to pre-flight values. Orientation of the optokinetic nystagmus eye velocity axis to gravito-inertial acceleration (GIA) during centrifugation was also unaltered by exposure to microgravity. Perceptual orientation to the GIA was maintained in-flight, and subjects did not report sensation of translation during constant velocity centrifugation. These studies suggest that percepts and ocular responses to tilt are determined by sensing the body vertical relative to the GIA. The findings also raise the possibility that 'artificial gravity' during the Neurolab flight counteracted adaptation of these otolith-ocular responses.

Acceleration↗

PubMed2002

The vestibulo-ocular reflex in three dimensions.

The purpose of this paper is to review the kinematics and dynamics of the vestibulo-ocular reflex (VOR) in three dimensions. We give a brief, didactic tutorial on vectors and matrices and their importance as representational schemes for describing the kinematics and dynamics of the angular and linear accelerations that activate the vestibular system. We show how the vectors associated with angular and linear head accelerations are transformed by the peripheral and central vestibular systems to drive the oculomotor system to produce eye movements in three-dimensional space. We also review critical questions and controversies related to the compensatory and orientation behavior of the VOR. One such question is how the central vestibular system distinguishes tilts of the head, which generate interaural linear acceleration from translations along the interaural axis. Another question is how the velocity-position integrator is implemented centrally. The review has been placed in the context of a model that explains the behavior of the VOR in three dimensions. Model processes have been related to peripheral and central neural behavior in order to gain insight into the nature of the three-dimensional organization and the controversial questions that are addressed.

Adaptation, Physiological↗

PubMed2002

Spatial orientation of caloric nystagmus.

The spatial orientation of the slow-phase eye velocity of caloric nystagmus was investigated in cynomolgus monkeys after all six semicircular canals had been plugged. Normal animals generate responses that have dominant convective components produced by movement of the endolymph in the lateral canal toward or away from gravity. As a result, the direction of horizontal slow-phase velocity induced by cold-water irrigation changes direction with changes in head position with regard to gravity. Plugging produced a dense overgrowth of bone that blocked the flow of endolymph, but the end organs were intact. Robust caloric nystagmus was elicited after recovery, but the horizontal (yaw) component was now always toward the stimulated (ipsilateral) side, regardless of head position re gravity. The induced caloric nystagmus had strong spatial orientation properties after canal plugging. With animals upright, the three-dimensional velocity vector of the caloric nystagmus was close to the yaw axis with small vertical and roll components. Roll components became stronger in supine and prone positions and vertical components were enhanced in the right- and left-side down positions. In each instance, the addition of the roll and vertical components moved the velocity vector of the nystagmus closer to the spatial vertical. Modeling supported the postulate that the caloric nystagmus after canal plugging is influenced by three factors: (1) a reduction in neural activity in the ampullary nerves on the stimulated side due to cooling of the nerves; (2) contraction of the endolymph in the closed space between the cupula and the plug due to cooling, which resulted in deflection of the cupula and hair cells toward the plug (ampullofugal deflection); and (3) alignment of eye velocity to gravity due to the orientation properties of velocity storage. Although convection is the most prominent factor in producing caloric responses in the normal state, our results suggest that alteration of nerve activity due to thermal effects, endolymph contraction or expansion, and velocity storage are also likely to contribute to the total response.

Animals↗

PubMed2002

The nodulus and uvula: source of cerebellar control of spatial orientation of the angular vestibulo-ocular reflex.

The nodulus and rostral-ventral uvula of the vestibulo-cerebellum play a critical role in orienting eye velocity of the slow component of the angular vestibulo-ocular reflex (aVOR) to gravito-inertial acceleration (GIA). This is done by altering the time constants of "velocity storage" in the vestibular system and by generating "cross-coupled" eye velocities that shift the eye velocity vector from along the body yaw axis to the yaw axis in a spatial frame. In this report, we show that eye velocity generated through the aVOR by constant velocity centrifugation in the monkey orients to the GIA in space, regardless of the position of the head with respect to the axis of rotation. We also show that, after removal of the nodulus and rostral-ventral uvula, the spatial orientation of eye velocity to the GIA is lost and that eye velocity is then purely driven by the semicircular canals in a body frame of reference. These findings are further confirmation that these regions of the vestibulo-cerebellum control spatial orientation of the aVOR.

Animals↗

PubMed2002

Compensatory and orienting eye movements induced by off-vertical axis rotation (OVAR) in monkeys.

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.

Animals↗

PubMed2002

Spatial orientation of caloric nystagmus in semicircular canal-plugged monkeys.

We studied caloric nystagmus before and after plugging all six semicircular canals to determine whether velocity storage contributed to the spatial orientation of caloric nystagmus. Monkeys were stimulated unilaterally with cold ( approximately 20 degrees C) water while upright, supine, prone, right-side down, and left-side down. The decline in the slow phase velocity vector was determined over the last 37% of the nystagmus, at a time when the response was largely due to activation of velocity storage. Before plugging, yaw components varied with the convective flow of endolymph in the lateral canals in all head orientations. Plugging blocked endolymph flow, eliminating convection currents. Despite this, caloric nystagmus was readily elicited, but the horizontal component was always toward the stimulated (ipsilateral) side, regardless of head position relative to gravity. When upright, the slow phase velocity vector was close to the yaw and spatial vertical axes. Roll components became stronger in supine and prone positions, and vertical components were enhanced in side down positions. In each case, this brought the velocity vectors toward alignment with the spatial vertical. Consistent with principles governing the orientation of velocity storage, when the yaw component of the velocity vector was positive, the cross-coupled pitch or roll components brought the vector upward in space. Conversely, when yaw eye velocity vector was downward in the head coordinate frame, i.e., negative, pitch and roll were downward in space. The data could not be modeled simply by a reduction in activity in the ipsilateral vestibular nerve, which would direct the velocity vector along the roll direction. Since there is no cross coupling from roll to yaw, velocity storage alone could not rotate the vector to fit the data. We postulated, therefore, that cooling had caused contraction of the endolymph in the plugged canals. This contraction would deflect the cupula toward the plug, simulating ampullofugal flow of endolymph. Inhibition and excitation induced by such cupula deflection fit the data well in the upright position but not in lateral or prone/supine conditions. Data fits in these positions required the addition of a spatially orientated, velocity storage component. We conclude, therefore, that three factors produce cold caloric nystagmus after canal plugging: inhibition of activity in ampullary nerves, contraction of endolymph in the stimulated canals, and orientation of eye velocity to gravity through velocity storage. Although the response to convection currents dominates the normal response to caloric stimulation, velocity storage probably also contributes to the orientation of eye velocity.

Animals↗

PubMedDate not supplied

Artificial gravity: a possible countermeasure for post-flight orthostatic intolerance.

Four payload crewmembers were exposed to sustained linear acceleration in a centrifuge during the Neurolab (STS-90) flight. In contrast to previous studies, otolith-ocular reflexes were preserved during and after flight. This raised the possibility that artificial gravity may have acted as a countermeasure to the deconditioning of otolith-ocular reflexes. None of the astronauts who were centrifuged had orthostatic intolerance when tested with head-up passive tilt after flight. Thus, centrifugation may also have helped maintain post-flight hemodynamic responses to orthostasis by preserving the gain of the otolith-sympathetic reflex. A comparison with two fellow Neurolab orbiter crewmembers not exposed to artificial gravity provided some support for this hypothesis. One of the two had hemodynamic changes in response to post-flight tilt similar to orthostatically intolerant subjects from previous missions. More data is necessary to evaluate this hypothesis, but if it were proven correct, in-flight short-radius centrifugation may help counteract orthostatic intolerance after space flight.

Acceleration↗