Contribution of Vestibular Commissural Pathways to Spatial Orientation of the Angular Vestibuloocular Reflex

Susan Wearne, Theodore Raphan, and Bernard Cohen

Departments of Neurology and Biophysics and Physiology, Mount Sinai School of Medicine, New York, 10029; and Computer and Information Sciences, Brooklyn College of the City University of New York, Brooklyn, New York 11210

    ABSTRACT
Abstract
Introduction
Methods
Results
Discussion
References

Wearne, Susan, Theodore Raphan, and Bernard Cohen. Contribution of vestibular commissural pathways to spatial orientation of the angular vestibuloocular reflex. J. Neurophysiol. 78: 1193-1197, 1997. During nystagmus induced by the angular vestibuloocular reflex (aVOR), the axis of eye velocity tends to align with the direction of gravitoinertial acceleration (GIA), a process we term "spatial orientation of the aVOR." We studied spatial orientation of the aVOR in rhesus and cynomolgus monkeys before and after midline section of the rostral medulla abolished all oculomotor functions related to velocity storage, leaving the direct optokinetic and vestibular pathways intact. Optokinetic afternystagmus and the bias component of off-vertical-axis rotation were lost, and the aVOR time constant was reduced to a value commensurate with the time constants of primary semicircular canal afferents. Spatial orientation of the aVOR, induced either during optokinetic or vestibular stimulation, was also lost. Vertical and roll aVOR time constants could no longer be lengthened in side-down or supine/prone positions, and static and dynamic tilts of the GIA no longer produced cross-coupling from the yaw to pitch and yaw to roll axes. Consequently, the induced nystagmus remained entirely in head coordinates after the lesion, regardless of the direction of the resultant GIA vector. Gains of the aVOR and of optokinetic nystagmus to steps of velocity were unaffected or slightly increased. These results are consistent with a model in which the direct aVOR pathways are organized in semicircular canal coordinates and spatial orientation is restricted to the indirect (velocity storage) pathways.

    INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References

The angular vestibuloocular reflex (aVOR) and optokinetic nystagmus (OKN) exhibit spatial orientation during nystagmus: eye velocity tends to align with gravitoinertial acceleration (GIA), which we define as the resultant of gravitational and centripetal accelerations (Angelaki and Hess 1995; Dai et al. 1991; Landsberg et al. 1965; Merfeld and Young 1995; Raphan and Cohen 1988; Raphan and Sturm 1991; Wearne et al. 1996). Modeling studies have proposed that these orientation properties are attributable solely to the velocity storage component, and that the direct pathways carrying activity for the high-frequency components of the aVOR are not spatially oriented (Raphan and Sturm 1991; Raphan et al. 1992, 1996). Behavioral data in monkey (Angelaki and Hess 1995; Dai et al. 1991; Merfeld and Young 1995; Wearne et al. 1996) and humans (Gizzi et al. 1994; Harris and Barnes 1987; Wearne 1993) support this hypothesis, but it has not been verified experimentally. On-side cross-coupling, the appearance of vertical components of eye velocity in response to yaw-axis stimulation, was greatly diminished in a midline-sectioned monkey with reduced velocity storage (Katz et al. 1991). However, only vertical and horizontal components of eye movements were recorded. Here we analyze three-dimensional eye movements to determine whether GIA tilts with regard to the head in any direction would affect the trajectories of eye velocity after velocity storage is abolished leaving only the direct pathways intact.

    METHODS
Abstract
Introduction
Methods
Results
Discussion
References

Juvenile rhesus monkeys (M502 and M613) were prepared with eye coils to record eye position in three dimensions, and the midline was surgically sectioned in the rostral medulla. The experiments conformed to the Principles of Laboratory Animal Care (National Institutes of Health Publication 85-23, Revised 1985), and were approved by the Institutional Animal Care and Use Committee. Spatial orientation of nystagmus was determined from OKN and optokinetic afternystagmus (OKAN) and from centrifugation. Quantitative data were mainly from M613, an animal with complete loss of velocity storage and no other oculomotor changes, with qualitative confirmation from M502 and M1188, a cynomolgus monkey from a previous study (Katz et al. 1991). Eye position recordings were two dimensional (horizontal and vertical) in M188. (See Katz et al. 1991 for details of surgery; Dai et al. 1994 and Yakushin et al. 1995 for details of eye movement recording; Dai et al. 1991, Raphan and Sturm 1991, and Wearne et al. 1996 for techniques of analyzing orientation vectors during OKN, OKAN, and centrifugation; and Holstein et al. 1996, for anatomic processing.)

For centrifugation, the animals were placed 25 cm from the axis of rotation either facing or back to motion. They were rotated with a constant angular acceleration of 40°/s2 to a final angular velocity of 400°/s. This induced an interaural centripetal component of linear acceleration of 1.2 g, causing a tilt of the GIA vector relative to gravity of 51° in the roll plane. The final angular velocity was maintained until eye velocity decayed to zero. Alternatively, animals were rotated facing in or out along the radius, which induced tilts of the GIA vector in the pitch plane.

Eye orientation was represented as Euler angles, phi , theta  and psi , describing rotations with the use of the Fick convention. The eye velocity vector in head coordinates, symbolized by omega  = [omega X, omega Y, omega Z], denoted vertical, torsional, and horizontal rotations that were obtained directly from the Euler angles and their derivatives (see Yakushin et al. 1995 for calibration of coil voltages). OKAN time constants were estimated by fitting a single exponential function to the decaying portion of eye velocity. During steps of angular velocity, velocity storage time constants were estimated by fitting a sum of two exponential functions to the decaying portion of eye velocity, with the cupula time constant constrained to 4 s (Raphan et al. 1979). The vestibular time constant quoted in the text is the central or velocity storage time constant, unless otherwise noted.

Slow phase velocities during centrifugation were related to the eigenvectors of the velocity storage system matrix by fitting a line to the three-dimensional eye velocity vector, starting 10 s after reaching constant angular head velocity. Because the decay of the eye velocity trajectory approaches the yaw eigenvector in the limit (Raphan and Sturm 1991), this line is a close approximation to the eigenvector. The magnitude of the axis shift in the head coordinate frame was computed as the difference between the yaw eigenvector and the Z-axis of the head. The line was projected into each cardinal head plane, and the angle made by this projection and the Z-axis was computed in each plane. Goodness of fit was verified by plotting the fitted eigenvector over the components of desaccaded eye velocity in the phase plane.

    RESULTS
Abstract
Introduction
Methods
Results
Discussion
References

A midline lesion that caused a complete loss of velocity storage (M613), but left all other oculomotor functions intact, extended from the rostral medulla, ventral and caudal to the abducens nuclei, toward the obex for ~3 mm. The lesion extended ~2 mm below the surface of the fourth ventricle, separating decussating fibers among the rostral medial vestibular nuclei (MVN), superior vestibular nuclei (SUN), and the prepositus nuclei. The slow rise of horizontal OKN was lost, and OKAN was virtually abolished. Horizontal OKAN time constants fell from 8.1 ± 1.9 (SD) s and 12.8 ± 2.9 s for rightward and leftward OKAN to1.7 ± 0.6 s and 1.8 ± 0.2 s, respectively (Fig. 1, A and C). Horizontal aVOR time constants fell from 7.6 ± 0.3 s and 19.1 ± 2.1 s for rightward and leftward eye velocities to 5.4 ± 0.2 s and 5.8 ± 2.1 s, respectively. The postoperative values are close to the time constant of afferent fibers from the semicircular canals (Goldberg and Fernandez 1971). This indicates that velocity storage was making little or no contribution to the induced response. Findings were similar in M502. Gaze was held stably in lateral positions in darkness, and the slow phases of the induced nystagmus were linear in M613 and M1188 (Katz et al. 1991), indicating that velocity-position integration was intact. Ocular counterrolling induced by off-vertical-axis rotation and centrifugation was unaffected, and average gains of the aVOR were unchanged. In response to a 60°/s step of angular velocity, aVOR gains were 0.88 ± 0.06 and 0.71 ± 0.04 for leftand right slow phases preoperatively and 0.94 ± 0.11 and0.79 ± 0.01 for left and right slow phases postoperatively. Average OKN gains were also unaffected (compare omega Z,Fig. 1, A and C) (see Katz et al. 1991).


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FIG. 1. Optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN) before (A and B) and after (C and D) midline section in M613. From top to bottom: stimulus (light ON/OFF), vertical eye velocity (omega X), roll eye velocity (omega Y), and horizontal eye velocity (omega Z). Three-dimensional phase plane graphs (B and D) were generated by plotting horizontal component of eye velocity vector, omega Z, against vertical and roll components, omega X and omega Y, with time as implicit parameter. Decaying portions of eye velocity, starting 2 s before offset of OKN and continuing until eye velocity reached 0, were used in these graphs. Responses for leftward (+Z) rotation are shown above abscissa, and responses for rightward (-Z) rotation are shown below abscissa. Stimulus velocities: 40°/s (A), and 60°/s (C).

Similar to conditions in humans (Gizzi et al. 1994), there was cross-coupling during OKN in the right-ear-down position, with a vertical component (omega X) appearing (Fig. 1A, light-on period) that persisted during OKAN (Fig. 1A, light-off period). Cross-coupling shifted the axis of eye rotation in the roll plane toward alignment with the acceleration of gravity (Ag, Fig. 1, top inset). As in most normal monkeys (Dai et al. 1991; Matsuo and Cohen 1984), this animal had a vertical OKAN asymmetry before lesion, producing larger roll-plane-axis shifts for upward (Fig. 1A, left; Fig. 1B,-omega X) than for downward (Fig. 1A, right; Fig. 1B, +omega X) cross-coupled components. The best-fitting three-dimensional tangent line (Fig. 1B, heavy black line), which estimated the eigenvector for the OKAN, tilted by 27° for downward cross-coupling and by 88° for upward cross-coupling. After operation, there was no cross-coupling during OKN and only minimal OKAN confined to the yaw axis (Fig. 1C). The estimated eigenvector of the declining eye velocity pitched forward slightly by 7° during leftward (+Z) OKAN and was approximately aligned with the yaw (Z) axis for rightward (-Z) OKAN (Fig. 1D). Similar results were obtained for pitch plane tilts. Thus reorientation to the GIA during OKN and OKAN was lost in all spatial planes after the midline lesion. This confirms and extends previous findings in the cynomolgus monkey (M1188) (Katz et al. 1991). It indicates that the direct optokinetic path is insensitive to the direction of the GIA, and that spatial orientation of OKN and OKAN is mediated entirely through velocity storage.

Centrifugation and rapid reorientation of the head during postrotatory nystagmus produced dynamic tilts of the GIA. Before surgery, yaw-axis centrifugation in the tangential orientation produced small roll (omega Y) and larger vertical (omega X) components of eye velocity, in addition to a compensatory horizontal (omega Z) nystagmus (Fig. 2A). With right ear out, horizontal eye velocity built to a peak of ~200°/s, to the left when back to motion (left) and to the right when facing motion (right). In the constant velocity phase of rotation, horizontal eye velocity decayed as a dual mode process combining the time constant of the cupula with that of the integrator (arrowhead labeled C + S). At ~10 s (2.5 cupula time constants) after the end of the angular acceleration (horizontal line under trace labeled omega Z), all activation of the canals had ceased, and eye velocity fell with the approximate time constant of velocity storage (arrowhead labeled S). A downward vertical cross-coupled component (+omega X) built during the acceleration, and decayed during the constant velocity period with a time constant close to that of the slow time constant of the horizontal trace.


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FIG. 2. Preoperative centrifugation with right ear out in M613. Stimulus induced 1-g component of centripetal acceleration, tilting resultant gravitoinertial acceleration (GIA) by 51° in animal's roll plane (inset). A: horizontal (omega Z), vertical (omega X), and roll (omega Y) components of eye velocity induced by centrifugation when back to motion (left) and facing motion (right). B-D: phase plane plots in roll (B), pitch (C), and yaw plane (D), showing decline in eye velocity during velocity storage component of response to centrifugation. Eigenvectors were estimated by fits to linear portions of 3-dimensional eye velocity vector from 10 s after end of angular acceleration to termination of responses. Projection of fitted eigenvector into each plane is shown as heavy black line, superimposed on eye velocity traces. In this and Fig. 3, only decaying portion of eye velocity is plotted, from onset of constant centrifuge velocity until eye velocity decayed to 0. Inset heads: orientation of phase planes with respect to head coordinate frame. E: decay of eye velocity in 3 dimensions (open circle ) and superimposed eigenvector fit (heavy black line). Three-dimensional components of fitted eigenvector are shown to right of 3-dimensional graph; +Z indicates eigenvectors fitted to decaying trajectory of dominant left horizontal eye velocity (+omega Z) response (left); -Z indicates eigenvectors fitted to dominant right horizontal eye velocity (-omega Z) response (right).

In two-dimensional phase plane graphs of the eye velocity vectors, the axis of eye rotation shifted primarily in the roll plane during centrifugation toward alignment with the tilted GIA (Fig. 2B). A small -omega Y (roll) component also developed, tilting the eigenvector slightly in the pitch plane (Fig. 2C), i.e., along the tangential component of the GIA. In the Y-X (yaw) plane, eye velocity decayed primarily along the X (pitch)-axis with a small roll component (Fig. 2D). In three dimensions, eye velocity initially decayed with pitch, roll, and yaw components (Fig. 2E). After the cupula response had decayed, the trajectory sharply curved toward the fitted eigenvector (Fig. 2E, heavy black line), and then decayed predominantly in the pitch-yaw plane as eye velocity approached zero. The monkey's vertical asymmetry was also present during centrifugation, producing larger roll-plane-axis shift angles for upward (Fig. 2B, -omega X) than for downward (Fig. 2B, +omega X) coupled components. For downward cross-coupled eye velocity (+omega Z), the eigenvector tilted in the roll plane by an angle of 41.3° [arctan (0.66/0.75) - eigenvector components, Fig. 2E, far right]. For upward cross-coupled eye velocity (-omega Z), it tilted by 59.5° [arctan (-0.85/-0.50)]. Thus the eigenvector overestimated the GIA tilt by 8.5° during upward cross-coupling and underestimated it by 10° during downward cross-coupling. Similar values were found by Dai et al. (1991) in cynomolgus monkeys during OKAN with the head statically tilted in roll.

The reduction in horizontal aVOR time constant due to the loss of velocity storage was reflected during centrifugation in both a smaller peak eye velocity and a shorter duration of nystagmus. Peak horizontal velocity (omega Z) fell from ~200°/s preoperatively to ~150°/s postoperatively (Fig. 3A). A sustained downward vertical component of ~15°/s (omega X) was present during GIA tilts. This was likely due to positional nystagmus (DeJong et al. 1980). Head tilts of 45°, nose down or ear down, induced similar sustained downward vertical nystagmus. Eye velocity decayed parallel to the yaw (Z) axis (Fig. 3B-D), in contrast to the tilted trajectory before lesion (Fig. 2B-D). Postoperatively, the decline along the Z-axis was shifted several degrees toward the pitch (+X) axis because of the positional nystagmus (Fig. 3, B and E). The lack of orientation to the GIA is most apparent in the three-dimensional eigenvector fit (Fig. 3E). The fitted eigenvector response was almost entirely along the yaw (Z) axis of the head, tilting by 0° for leftward (+omega Z) and by 2.8° for rightward (-omega Z) eye velocity. Results were the same when the GIA was tilted with centripetal acceleration directed along the positive and negative poles of the nasooccipital axes. Preoperatively, the eye rotation axis approximately aligned with the 51° tilt of the GIA during pitch plane tilts. After surgery, reorientation of the axis of eye rotation was lost, and the eye velocity vector decayed purely along the yaw axis. All reorientation during rapid tilts of the head during postrotatory nystagmus was also lost after midline medullary section.


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FIG. 3. Postoperative centrifugation with right ear out. Scheme as in Fig. 2. A: there was no cross-coupling from horizontal to vertical after operation. B-D: in 2-dimensional phase plane graphs with superimposed eigenvector fits, eye velocity (open circle ) decayed, with constant positive vertical offset, parallel to head Z-axis because of positional nystagmus. E: decay of eye velocity in 3 dimensions (open circle ) and 3-dimensional eigenvector fit (heavy black line). Eigenvector components at right of E were 0.00 for X-component (+Z responses) and -0.05 for -Z responses, compared with preoperative values of 0.66 and -0.85, respectively. These postoperative values correspond to roll plane tilts of 0 and 2.8°.

    DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References

This study shows that spatial orientation of the aVOR is lost in all dimensions after midline lesions of the rostral medulla. The results were the same whether the GIA was tilted statically or dynamically, and whether velocity storage was excited through the visual or vestibular systems. This supports the postulate that there is no spatial orientation of the direct pathways of either OKN or the aVOR and that orientation of eye velocity to the GIA is mediated solely by indirect pathways that subserve velocity storage (Raphan and Cohen 1988; Raphan and Sturm 1991; Wearne et al. 1996). It also indicates that portions of the vestibular commissure in rostral MVN, utilized to produce velocity storage and its spatial orientation, are separate from those that produce rapid changes in eye velocity either from the semicircular canals or the visual system. They are also discrete from the otolith-ocular pathways, which produce ocular counterrolling.

    ACKNOWLEDGEMENTS

  We thank V. Rodriguez for technical assistance and for help in producing the figures.

  This work was supported by National Institutes of Health Grants NS-00294, DC-01705, EY-04148, and EY-01867.

    FOOTNOTES

  Address for reprint requests: B. Cohen, Dept. of Neurology, Box 1135, Mt. Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029.

  Received 17 March 1997; accepted in final form 9 May 1997.

    REFERENCES
Abstract
Introduction
Methods
Results
Discussion
References

0022-3077/97 $5.00 Copyright ©1997 The American Physiological Society