The Management and Imaging of Vestibular Schwannomas.

Vestibular schwannomas are the most common cerebellopontine angle tumor. During the past century, the management goals of vestibular schwannomas have shifted from total resection to functional preservation. Current treatment options include surgical resection, stereotactic radiosurgery, and observation. Imaging has become a crucial part of the initial screening, evaluation, and follow-up assessment of vestibular schwannomas. Recognizing and understanding the management objectives, various treatment modalities, expected posttreatment findings, and complications allows the radiologist to play an essential role in a multidisciplinary team by providing key findings relevant to treatment planning and outcome assessment. The authors provide a comprehensive discussion of the surgical management, role of radiation therapy and observation, imaging differential, and pre- and posttreatment imaging findings of vestibular schwannomas.

Ocular compensation due to labyrinthine input during natural motion.

With recent technical developments, it has become possible to study eye and head movements in all angular and linear degrees of freedom during natural activities such as standing and treadmill ambulation. Such studies have revealed that normal human gaze stabilization during ambulation is accomplished not only by ocular rotation in response to head rotation, but also by head translation coordinated with head rotation as appropriate to viewing distance. Typically, head translation in a given direction is coupled via an active mechanism with antiphase rotation in the opposite direction, accomplishing some gaze stabilization for near targets and supplementing the vestibulo-ocular reflex (VOR). Subunity angular VOR gain (eye velocity/head velocity) not only is observed during most natural activities, but also minimizes the disturbance to retinal image stability so that excellent visual acuity can be obtained. The generation of eye movements compensating for head motion during ambulation can be quantitatively modeled as an additive combination of semicircular canal responses, with otolith responses scaling by inverse viewing distance, so angular VOR gain correlates poorly with gaze stability. Compensatory eye movements during self-generated head rotations appear driven to a significant extent by nonvestibular mechanisms since they cannot be modeled as an additive combination of otolith and canal responses. People with unilateral vestibular deafferentation have normal gaze stability during natural activities such as standing, walking, and running, although gaze stability is impaired in bilateral deafferentation. Limitation of head motion during natural activities is a common strategy in those with reduced peripheral vestibular sensitivity.

New tests of vestibular function.

The vestibulo-ocular reflex (VOR) is the only drive for short-latency eye movements stabilizing the retina during externally imposed, sudden, high-head accelerations. New strategies can exploit this unique VOR feature to study it under conditions relevant to the daily lives of patients, and to exclude the contributions from confounding nonvestibular mechanisms. Testing of the yaw vestibulo-ocular reflex (VOR) during random, whole-body rotational transients at < or = 2800 degrees/s2 delivered about centered and eccentric axes enables measurement of gains and millisecond latencies of the canal and otolith VORs in humans. Repeated measurements in acute unilateral deafferentation show sequential recovery of canal and otolith VORs to contralesional rotation, but severe and permanent deficits to ipsilesional rotation. Patients with bilateral loss of caloric responses show severe bilateral loss of VORs to transient rotation, suggesting that the apparent preservation of their VORs during sinusoidal rotations at moderate frequencies may be due instead to somatosensory inputs. Since visual acuity is degraded by retinal image motion, dynamic visual acuity (DVA) measured during imposed head-on-body or whole-body transient motion can correlate closely with VOR performance only if optotypes are presented during directionally and temporally unpredictable, high-acceleration head motion. Prediction and efference copy are relentlessly employed by vestibulopathic patients to enable good DVA during predictable or low-acceleration head motion. The linear VOR to transient lateral acceleration is strongly dependent upon viewing distance. The latency of this otolith VOR is slightly longer and more variable than the canal VOR. Unlike the canal VOR, the otolith VOR does not develop a strong directional asymmetry in unilateral deafferentation. The otolith VOR is bilaterally attenuated in bilateral vestibulopathy, and loses target distance dependence in cerebellar degeneration.

Effects of vestibular and cerebellar deficits on gaze and torso stability during ambulation.

We measured gaze, head, and torso stability during ambulation to determine how vestibulo-ocular reflex dysfunction caused by unilateral vestibulopathy, bilateral vestibulopathy, and cerebellar dysfunction might affect image stabilization on the retina. Subjects were tested during standing, walking, and running on a treadmill. Gaze velocity, vestibulo-ocular reflex gain, and head velocities were calculated from angular positions of the eye and head, as well as linear positions of the head and trunk. Mean gaze velocity with a visible, distant target was below 4 degrees /second for all measurement conditions in control and vestibulopathic subjects. The performance of unilaterally vestibulopathic subjects was indistinguishable from that of control subjects except that the former had less vertical translation during walking. Bilaterally vestibulopathic subjects demonstrated less head translation than control subjects but had higher gaze velocity. In subjects with cerebellar dysfunction, gaze velocity was elevated by pathologic nystagmus, but head movements were similar to those of control subjects.

Vision and vestibular adaptation.

This article summarizes six recent degree-of-freedom studies of visual-vestibular interaction during natural activities and relates the findings to canal-otolith interactions evaluated during eccentric axis rotations. Magnetic search coils were used to measure angular eye and head movements of young and elderly subjects. A flux gate magnetometer was used to measure three-dimensional head translation. Three activities were studied: standing quietly, walking in place, and running in place. Each activity was evaluated with three viewing conditions: a visible target viewed normally, a remembered target in darkness, and a visible target viewed with x2 binocular telescopic spectacles. Canal-otolith interaction was assessed with passive, whole-body, transient, and steady-state rotations in pitch and yaw at multiple frequencies about axes that were either oculocentric or eccentric to the eyes. For each rotational axis, subjects regarded visible and remembered targets located at various distances. Horizontal and vertical angular vestibulo-ocular reflexes were demonstrable in all subjects during standing, walking, and running. When only angular gains were considered, gains in both darkness and during normal vision were less than 1.0 and were generally lower in elderly than in young subjects. Magnified vision with x2 telescopic spectacles produced only small gain increases as compared with normal vision. During walking and running all subjects exhibited significant mediolateral and dorsoventral head translations that were antiphase locked to yaw and pitch head movements, respectively. These head translations and rotations have mutually compensating effects on gaze in a target plane for typical viewing distances and allow angular vestibulo-ocular reflex gains of less than 1.0 to be optimal for gaze stabilization during natural activities. During passive, whole-body eccentric pitch and yaw head rotations, vestibulo-ocular reflex gain was modulated as appropriate to stabilize gaze on targets at the distances used. This modulation was evident within the first 80 msec of onset of head movement, too early to be caused by immediate visual tracking. Modeling suggests a linear interaction between canal signals and otolith signals scaled by the inverse of target distance. Vestibulo-ocular reflex performance appears to be adapted to stabilize gaze during translational and rotational perturbations that occur during natural activities, as is appropriate for relevant target distances. Although immediate visual tracking contributes little to gaze stabilization during natural activities, visual requirements determine the performance of vestibulo-ocular reflexes arising from both canals and otoliths.

Asymmetry of ocular motor and perceptual vestibular processing in humans with unilateral vestibular deafferentation.

To investigate the effect of asymmetrical vestibular input on the perceived straight-ahead direction, we compared 7 subjects (age 59 +/- 8 yrs, mean +/- SD) who had chronic (>10 mos) unilateral vestibular deafferentation with 10 age matched controls (age 61+/-6 younger controls (age 28 +/- 7 yrs). Despite the age difference, the two control groups performed similarly and were therefore pooled. Eye and head movements were recorded using search coils as subjects underwent 30 s trials of sinusoidal, whole body oscillation (0.4-2 Hz, peak velocities 0-120 degrees /s) in darkness while attempting to maintain gaze on a remembered target 5 m distant. As a control, most stimulus oscillations were randomly superimposed on an imperceptible, constant velocity of +/-0.5 degrees /s that produced a whole-body offset of 15 degrees by the end of the trial. Following oscillation, subjects remained motionless in darkness and were asked to orient both gaze and a manipulandum to the remembered target location. In control subjects, mean final gaze and manipulandum positions were within 15 degrees of the target for all testing conditions. There was no dependence of final gaze and manipulandum positions on the frequency or velocity of the preceding whole-body oscillations (p > 0.05). In four of seven unilaterally deafferented subjects there was an ipsilesional bias of final eye position of > or =10 degrees. These subjects moved both eye and manipulandum to the ipsilesional side, with the error increasing at higher stimulus velocities. For the 120 degrees /s peak head velocity, mean ipsilesional gaze bias ranged from 10-37 degrees and mean manipulandum bias ranged from 26-108 degrees. Although the errors depended on velocity p < 0.01), errors were independent of frequency (p > 0.1). In the remaining three subjects with vestibular deafferentation, final gaze and manipulandum positions [were not statistically different from controls.] Early gain (eye velocity / head velocity) of the VOR averaged 0.82 +/- 0.01 for the first 10 s of all trials and was similar in all groups (p > 0.1). Gain during the final 10 s gain averaged 0.78 +/- 0.01 for control subjects, but was significantly lower at 0.70 +/- 0.01 for unilaterally deafferented subjects, whose eye positions reached the limit of the ocular motor range. We conclude that many humans with chronic unilateral vestibular deafferentation have a large ipsilesional dynamic bias of eye position and the perceived straight ahead direction reflecting persistent asymmetry of vestibular processing.

Human gaze stabilization during natural activities: translation, rotation, magnification, and target distance effects.

Stability of images on the retina was determined in 14 normal humans in response to rotational and translational perturbations during self-generated pitch and yaw, standing, walking, and running on a treadmill. The effects on image stability of target distance, vision, and spectacle magnification were examined. During locomotion the horizontal and vertical velocity of images on the retina was <4 degrees /s for a visible target located beyond 4 m. Image velocity significantly increased to >4 degrees /s during self-generated motion. For all conditions of standing and locomotion, angular vestibulo-ocular reflex (AVOR) gain was less than unity and varied significantly by activity, by target distance, and among subjects. There was no significant correlation(P > 0.05) between AVOR gain and image stability during standing and walking despite significant variation among subjects. This lack of correlation is likely due to translation of the orbit. The degree of orbital translation and rotation varied significantly with activity and viewing condition in a manner suggesting an active role in gaze stabilization. Orbital translation was consistently antiphase with rotation at predominant frequencies <4 Hz. When orbital translation was neglected in computing gaze, computed image velocities increased. The compensatory effect of orbital translation allows gaze stabilization despite subunity AVOR gain during natural activities. Orbital translation decreased during close target viewing, whereas orbital rotation decreased while wearing telescopic spectacles. As the earth fixed target was moved closer, image velocity on the retina significantly increased (P < 0.05) for all activities except standing. Latency of the AVOR increased slightly with decreasing target distance but remained <10 ms for even the closest target. This latency was similar in darkness or light, indicating that the visual pursuit tracking is probably not important in gaze stabilization. Trials with a distant target were repeated while subjects wore telescopic spectacles that magnified vision by 1.9 or 4 times. Gain of the AVOR was enhanced by magnified vision during all activities, but always to a value less than spectacle magnification. Gain enhancement was greatest during self-generated sinusoidal motion at 0.8 Hz and was less during standing, walking, and running. Image slip velocity on the retina increased with increasing magnification. During natural activities, slip velocity with telescopes increased most during running and least during standing. Latency of the visually enhanced AVOR significantly increased with magnification (P < 0.05), probably reflecting a contribution of the visual pursuit system. The oculomotor estimate of target distance was inferred by measuring binocular convergence, as well as from monocular parallax during head translation. In darkness, target distance estimates obtained by both techniques were less accurate than in light, consistently overestimating for near and underestimating for far targets.

Effect of adaptation to telescopic spectacles on the initial human horizontal vestibuloocular reflex.

Gain of the vestibuloocular reflex (VOR) not only varies with target distance and rotational axis, but can be chronically modified in response to prolonged wearing of head-mounted magnifiers. This study examined the effect of adaptation to telescopic spectacles on the variation of the VOR with changes in target distance and yaw rotational axis for head velocity transients having peak accelerations of 2,800 and 1,000 degrees /s(2). Eye and head movements were recorded with search coils in 10 subjects who underwent whole body rotations around vertical axes that were 10 cm anterior to the eyes, centered between the eyes, between the otoliths, or 20 cm posterior to the eyes. Immediately before each rotation, subjects viewed a target 15 or 500 cm distant. Lighting was extinguished immediately before and was restored after completion of each rotation. After initial rotations, subjects wore 1.9x magnification binocular telescopic spectacles during their daily activities for at least 6 h. Test spectacles were removed and measurement rotations were repeated. Of the eight subjects tolerant of adaptation to the telescopes, six demonstrated VOR gain enhancement after adaptation, while gain in two subjects was not increased. For all subjects, the earliest VOR began 7-10 ms after onset of head rotation regardless of axis eccentricity or target distance. Regardless of adaptation, VOR gain for the proximate target exceeded that for the distant target beginning at 20 ms after onset of head rotation. Adaptation increased VOR gain as measured 90-100 ms after head rotation onset by an average of 0.12 +/- 0.02 (SE) for the higher head acceleration and 0.19 +/- 0.02 for the lower head acceleration. After adaptation, four subjects exhibited significant increases in the canal VOR gain only, whereas two subjects exhibited significant increases in both angular and linear VOR gains. The latencies of linear and early angular target distance effects on VOR gain were unaffected by adaptation. The earliest significant change in angular VOR gain in response to adaptation occurred 50 and 68 ms after onset of the 2,800 and 1,000 degrees /s(2) peak head accelerations, respectively. The latency of the adaptive increase in linear VOR gain was approximately 50 ms for the peak head acceleration of 2,800 degrees /s(2), and 100 ms for the peak head acceleration of 1,000 degrees /s(2). Thus VOR gain changes and latency were consistent with modification in the angular VOR in most subjects, and additionally in the linear VOR in a minority of subjects.

Gaze stabilization during dynamic posturography in normal and vestibulopathic humans.

Dynamic posturography by measurement of center of pressure (COP) is a widely employed technique for evaluating the vestibular system. However, the relationship of COP motion to vestibulo-ocular reflex (VOR) function and image stability on the retina has not been determined previously. To assess these relationships, we report gaze, head, and trunk stability during dynamic posturography in 11 normal volunteers, 7 subjects with unilateral vestibular lesions, and 3 subjects with bilateral vestibular lesions. Posturographic tasks consisted of standing still and standing on a platform that was sliding (0.2 Hz), tilting (0.1 Hz), or covered with a foam cushion 6 cm thick while tilting (0.1 Hz). Each perturbation was imposed in the anterior-posterior and repeated in the medial-lateral direction, in both light and darkness. Subjects viewed (or in darkness remembered) a target located 50, 100, or 500 cm distant. COP, angular eye position, and angular and linear orbit and trunk positions were measured using magnetic search coils and flux gate magnetometer sensors. With the target visible, the velocity of image motion on the retina was on average always less than 1 degree/s, well within the range consistent with high visual acuity. In darkness, gaze velocity increased for normal and vestibulopathic subjects. During tilt, vestibulopathic subjects had a significantly greater gaze velocity than controls. Gain of the angular VOR (eye velocity/head velocity) was significantly lower in darkness than in light and in vestibulopathic as compared to control subjects. Gain of the VOR was significantly correlated with gaze instability, but variation in VOR gain accounted for only 20-40% of the variance. In darkness, the velocity of the COP was significantly greater in vestibulopathic than control subjects for every condition tested. In light, this difference was small and often not significant. Although spectral analysis of the COP indicated frequencies above 1 Hz that were not observed in motion of the trunk and orbit, root mean square (RMS) velocities of the trunk and orbit in the horizontal plane were higher in darkness and in vestibulopathic subjects, mirroring COP findings. Only in vestibulopathic subjects tested in darkness was there a correlation between COP velocity and gaze velocity; COP velocity was otherwise uncorrelated with gaze. Gaze velocity was greater with near than with distant targets. Vertical VOR gain was higher with near targets. No other significant effects of target distance were found. Head movement strategy, VOR gain, and COP were all unaffected by target proximity. These data show that gaze velocity measurements during dynamic posturography in darkness are sensitive to vestibular loss. With a visible target, both COP and gaze stability of vestibulopathic subjects are difficult to distinguish from normal. During visual feedback, it is likely that image stabilization over the range of frequencies tested is achieved through better head stability and through visual tracking, allowing vestibulopathic subjects to maintain adequate visual acuity.

A linear canal-otolith interaction model to describe the human vestibulo-ocular reflex.

A control systems model of the vestibulo-ocular reflex (VOR) originally derived for yaw rotation about an eccentric axis (Crane et al. 1997) was applied to data collected during ambulation and dynamic posturography. The model incorporates a linear summation of an otolith response due to head translation scaled by target distance, adding to a semi-circular canal response that depends only on angular head rotation. The results of the model were compared with human experimental data by supplying head angular velocity as determined by magnetic search coil recording as the input for the canal branch of the model and supplying linear acceleration as determined by flux gate magnetometer measurements of otolith position. The model was fit to data by determining otolith weighting that enabled the model to best fit the data. We fit to the model experimental data from normal subjects who were: standing quietly, walking, running, or making active sinusoidal head movements. We also fit data obtained during dynamic posturography tasks of: standing on a platform sliding in a horizontal plane at 0.2 Hz, standing directly on a platform tilting at 0.1 Hz, and standing on the tilting platform buffered by a 5-cm thick foam rubber cushion. Each task was done with the subject attending a target approximately 500, 100, or 50 cm distant, both in light and darkness. The model accurately predicted the observed VOR response during each test. Greater otolith weighting was required for near targets for nearly all activities, consistent with weights for the otolith component found in previous studies employing imposed rotations. The only exceptions were for vertical axis motion during standing, sliding, and tilting when the platform was buffered with foam rubber. In the horizontal axis, the model always fit near target data better with a higher otolith component. Otolith weights were similar with the target visible and in darkness. The model predicts eye movement during both passive whole-body rotation and free head movement in space implying that the VOR is controlled by a similar mechanism during both situations. Factors such as vision, proprioception, and efference copy that are available during head free motion but not during whole-body rotation are probably not important to gaze stabilization during ambulation and postural stabilizing movement. The linearity of the canal-otolith interaction was tested by re-analysis of the whole body rotation data on which the model is based (Crane et al. 1997). Normalized otolith-mediated gain enhancement was determined for each axis of rotation. This analysis uncovered minor non-linearities in the canal-otolith interaction at frequencies above 1.6 Hz and when the axis of rotation was posterior to the head.

Horizontal vestibulo-ocular reflex and head stability in response to torso perturbations during visual search.

Eye, head, and torso movements were recorded using magnetic search coils while six normal human subjects made unconstrained eye and head movements as they searched for targets in a panoramic visual environment. Torso movements were imposed by pseudorandom rotations of a servomotor-driver chair in which subjects were seated; body motion was partially transmitted to the head as a perturbation. Horizontal vestibulo-ocular reflex (VOR) gain (eye velocity divided by head velocity) and head gain (head velocity divided by torso velocity) were determined. Measurements were performed with unaided vision and while subjects wore x4 binocular telescopic spectacles. Since the head was free to move during the experiment, much of the perturbation delivered to the torso was compensated by head rotation on the neck. During the 50 ms immediately following chair rotation, the head corrected 98% of the torso motion. For the interval 50-80 ms after the perturbation 81-85% of the perturbation was corrected by head movement. The degree of head compensation did not significantly depend on magnification or type of visual target. The density distribution for VOR gain was calculated over the entire course of each trial and was found to be sharply centered between 0.9 and 1.0 for trials with unmagnified vision. The gain density distribution with x4 telescopes was broader and centered around 1.5, reflecting visual enhancement. Gain of the VOR was also determined during four discrete epochs covering the period from 50 ms before to 130 ms after the onset of each imposed torso rotation. The first, second, and fourth epochs were 50 ms each, while the third epoch was 30 ms. The torso began to rotate in the second epoch (0-50 ms), and the onset of head rotation was in the third epoch (50-80 ms). Gains of the VOR determined during the first three epochs were in response to self-generated head rotation and were not significantly different from each other, averaging 1.0+/-0.4 (n=1604, mean+/-SD) with unaided vision and increased significantly (P<0.05) to 1.4+/-0.6 (n=2464) with telescopic spectacles. Gain of the VOR during the fourth (80-130 ms) epoch was in response to the imposed perturbation; this averaged 0.9+/-0.3 (n=1380) with unaided vision and increased significantly to 1.1+/-0.4 (n=2185) with telescopic spectacles. The wearing of telescopic spectacles thus induced an enhancement of VOR gain, which was dependent on the context of the associated head movement. The greater enhancement of VOR gain during self-generated head movement suggests that the large enhancement may be at least partially mediated by the motor program itself. However, the smaller, but still significant gain enhancement with telescopic spectacles observed during unpredictable, externally imposed head motion had a latency too short to be mediated by visual pursuit. We propose that the smaller gain enhancement during passive rotation is due to a small, context-dependent, parametric increase in the gain of canal or proprioceptive mediated eye movements.

Human horizontal vestibulo-ocular reflex initiation: effects of acceleration, target distance, and unilateral deafferentation.

The vestibulo-ocular reflex (VOR) generates compensatory eye movements in response to angular and linear acceleration sensed by semicircular canals and otoliths respectively. Gaze stabilization demands that responses to linear acceleration be adjusted for viewing distance. This study in humans determined the transient dynamics of VOR initiation during angular and linear acceleration, modification of the VOR by viewing distance, and the effect of unilateral deafferentation. Combinations of unpredictable transient angular and linear head rotation were created by whole body yaw rotation about eccentric axes: 10 cm anterior to eyes, centered between eyes, centered between otoliths, and 20 cm posterior to eyes. Subjects viewed a target 500, 30, or 15 cm away that was extinguished immediately before rotation. There were four stimulus intensities up to a maximum peak acceleration of 2,800 degrees/s2. The normal initial VOR response began 7-10 ms after onset of head rotation. Response gain (eye velocity/head velocity) for near as compared with distant targets was increased as early as 1-11 ms after onset of eye movement; this initial effect was independent of linear acceleration. An otolith mediated effect modified VOR gain depending on both linear acceleration and target distance beginning 25-90 ms after onset of head rotation. For rotational axes anterior to the otoliths, VOR gain for the nearest target was initially higher but later became less than that for the far target. There was no gain correction for the physical separation between the eyes and otoliths. With lower acceleration, there was a nonlinear reduction in the early gain increase with close targets although later otolith-mediated effects were not affected. In subjects with unilateral vestibular deafferentation, the initial VOR was quantitatively normal for rotation toward the intact side. When rotating toward the deafferented side, VOR gain remained less than half of normal for at least the initial 55 ms when head acceleration was highest and was not modulated by target distance. After this initial high acceleration period, gain increased to a degree depending on target distance and axis eccentricity. This behavior suggests that the commissural VOR pathways are not modulated by target distance. These results suggest that the VOR is initially driven by short latency ipsilateral target distance dependent and bilateral target-distance independent canal pathways. After 25 ms, otolith inputs contribute to the target distance dependent pathway. The otolith input later grows to eventually dominate the target distance mediated effect. When otolith input is unavailable the target distance mediated canal component persists. Modulation of canal mediated responses by target distance is a nonlinear effect, most evident for high head accelerations.

Latency of voluntary cancellation of the human vestibulo-ocular reflex during transient yaw rotation.

Volitional suppression of the initial vestibuloocular reflex (VOR) was studied in ten normal humans, aged 29+/-8 years (mean+/-standard deviation, SD), who were rotated about a vertical axis centered between the otoliths. Rotations consisted of steps in acceleration of 2800, 1600, 1000, or 500 degrees/S2 delivered at unpredictable times in unpredictable directions in the horizontal plane. As a test of the VOR, subjects were asked to attend to an earth-fixed target located 500 cm away that was either continuously visible or extinguished immediately before rotation. The gain of the VOR (angular eye velocity/angular head velocity) was 0.78+/-0.01 (mean+/-standard error of the mean, SE) during the period 35-45 ms after the onset of head rotation and 0.952+/-0.005 during the period 125-135 ms after the onset of head rotation. Subsequent rotations were performed during viewing of a target that moved with the head (cancellation). Cancellation was studied under three conditions of target visibility: (1) with the target always visible; (2) with the target always extinguished immediately prior to head rotation; or (3) with the target unpredictably extinguished half of the time immediately before each rotation. Cancellation responses showed individual idiosyncrasies, but certain features were common to most subjects. During cancellation, the VOR response generally differed from the earth-fixed target condition in that there was usually a small decrease in slow-phase VOR gain followed by an oppositely directed saccade. During the highest acceleration (2800 degrees/s2), the latency of the earliest statistically significant gain decrease for cancellation, as compared with the earth-fixed target condition, averaged 48+/-5 ms (mean+/-SE) from the onset of head rotation, although it was significantly shorter in one subject who had an onset at 14+/-2 ms. The latency of cancellation increased as head acceleration decreased such that, for each stimulus, cancellation began when the head was displaced an average of 1.4+/-0.1 degrees (-/+SD). Because VOR cancellation generally occurred before the availability of visual feedback or under conditions when vision was never permitted, it is inferred that cancellation is triggered by a threshold eye position or an estimate of head rotation based on integration of vestibular afferents. Cancellation occurred significantly earlier with a visible target than with an extinguished target only at the lowest peak head acceleration of 500 degrees/s2. Corrective saccades with a visible target occurred later for head accelerations of 500 and 1000 degrees/s2 than for greater head accelerations. Significant effects of target illumination on the latencies of both saccades and cancellation occurred at least 80-90 ms after the onset of head rotation, consistent with the earliest available visual feedback. This longer latency of saccades for visible as compared with extinguished targets may be analogous to a release of fixation, as occurs with express saccades. The latency difference due to target visibility was not related to prediction, since it was unchanged under conditions of random target illumination.

The human horizontal vestibulo-ocular reflex during combined linear and angular acceleration.

We employed binocular magnetic search coils to study the vestibulo-ocular reflex (VOR) and visually enhanced vestibulo-ocular reflex (VVOR) of 15 human subjects undergoing passive, whole-body rotations about a vertical (yaw) axis delivered as a series of pseudorandom transients and sinusoidal oscillations at frequencies from 0.8 to 2.0 Hz. Rotations were about a series of five axes ranging from 20 cm posterior to the eyes to 10 cm anterior to the eyes. Subjects were asked to regard visible or remembered targets 10 cm, 25 cm, and 600 cm distant from the right eye. During sinusoidal rotations, the gain and phase of the VOR and VVOR were found to be highly dependent on target distance and eccentricity of the rotational axis. For axes midway between or anterior to the eyes, sinusoidal gain decreased progressively with increasing target proximity, while, for axes posterior to the otolith organs, gain increased progressively with target proximity. These effects were large and highly significant. When targets were remote, rotational axis eccentricity nevertheless had a small but significant effect on sinusoidal gain. For sinusoidal rotational axes midway between or anterior to the eyes, a phase lead was present that increased with rotational frequency, while for axes posterior to the otolith organs phase lag increased with rotational frequency. Transient trials were analyzed during the first 25 ms and from 25 to 80 ms after the onset of the head rotation. During the initial 25 ms of transient head rotations, VOR and VVOR gains were not significantly influenced by rotational eccentricity or target distance. Later in the transient responses, 25-80 ms from movement onset, both target distance and eccentricity significantly influenced gain in a manner similar to the behavior during sinusoidal rotation. Vergence angle generally remained near the theoretically ideal value during illuminated test conditions (VVOR), while in darkness vergence often varied modestly from the ideal value. Regression analysis of instantaneous VOR gain as a function of vergence demonstrated only a weak correlation, indicating that instantaneous gain is not likely to be directly dependent on vergence. A model was proposed in which linear acceleration as sensed by the otoliths is scaled by target distance and summed with angular acceleration as sensed by the semicircular canals to control eye movements. The model was fit to the sinusoidal VOR data collected in darkness and was found to describe the major trends observed in the data. The results of the model suggest that a linear interaction exists between the canal and otolithic inputs to the VOR.

Vestibular catch-up saccades in labyrinthine deficiency.

During rapid head rotations, saccades ipsiversive with compensatory vestibulo-ocular reflex (VOR) slow phases may augment the deficient VOR and assist gaze stabilization in space. The present experiments compared these vestibular catch-up saccades (VCUSs) with visually and memory-guided saccades. To characterize VCUSs and their relationship to deficiency of the initial VOR, we delivered random, whole-body transients of 1000 and 2800 degrees/s2 peak yaw acceleration around four different eccentric vertical axes in eight unilaterally and one bilaterally vestibulopathic subjects, as well as nine age-matched normal subjects. Eye and head movements were sampled at 1200 Hz using magnetic search coils. Subjects fixed targets at either 500 or 15 cm distance immediately before unpredictable onset of rotation in darkness. Under all testing conditions, normal subjects exhibited only compensatory vestibular slow phases and occasional anticompensatory quick phases. This behavior was also typical of unilaterally vestibulopathic subjects rotated contralesionally. When rotated ipsilesionally, however, vestibulopathic subjects had deficient slow-phase VOR gain with prolonged latency, and six of the nine exhibited saccadic movements in the compensatory direction (VCUSs). Higher head accelerations preferentially evoked VCUSs, but there were no preferred combinations of target distances and eccentric rotation axes. Peak velocities and durations of VCUSs increased with saccade amplitude. The latency distribution for VCUSs peaked around 70 ms, substantially shorter than reported for either visually guided express saccades or vestibular memory contingent saccades. The latency of each VCUS was highly correlated with the gaze error prior to that VCUS. The amplitude of VCUSs was calibrated to gaze position error, such that VCUSs reduced gaze error by an average of 37%. Thus when VOR slow-phase responses cannot compensate fully for head rotation, vestibular gaze position error can nevertheless calibrate the programming of VCUSs to augment the deficient VOR, much like catch-up saccades substitute for deficient visual pursuit.

Initial vestibulo-ocular reflex during transient angular and linear acceleration in human cerebellar dysfunction.

During transient, high-acceleration rotation, performance of the normal vestibulo-ocular reflex (VOR) depends on viewing distance. With near targets, gain (eye velocity/head velocity) enhancement is manifest almost immediately after ocular rotation begins. Later in the response, VOR gain depends on both head rotation and translation; gain for near targets is decreased for rotation about axes anterior to the otoliths and augmented for rotation about axes posterior to the otoliths. We sought to determine whether subjects with cerebellar dysfunction have impaired modification of the VOR with target distance. Eleven subjects of average age 48 +/- 16 years (mean +/- standard deviation, SD) with cerebellar dysfunction underwent transients of directionally unpredictable whole-body yaw rotation to a peak angular acceleration of 1000 or 2800 degrees/s2 while viewing a target either 15 cm or 500 cm distant. Immediately before onset of head rotation, the lights were extinguished and were relit only after the rotation was completed. The axis of head rotation was varied so that it was located 20 cm behind the eyes, 7 cm behind the eyes (centered between the otoliths), centered between the eyes, or 10 cm anterior to the eyes. Angular eye and head positions were measured with magnetic search coils. The VOR in subjects with cerebellar dysfunction was compared with the response from 12 normal subjects of mean age 25 +/- 4 years. In the period 35-45 ms after onset of 2800 degrees/s2 head rotation, gain was independent of rotational axis. In this period, subjects with cerebellar dysfunction had a mean VOR gain of 0.5 +/- 0.2, significantly lower than the normal range of 1.0 +/- 0.2. During a later period, 125-135 ms after head rotation about an otolith-centered axis, subjects with cerebellar dysfunction had a mean VOR gain of 0.67 +/- 0.46, significantly lower than the value of 1.06 +/- 0.14 in controls. Unlike normal subjects, those with cerebellar dysfunction did not show modification of VOR gain with target distance in the early response and only one subject showed a correct effect of target distance in the later response. The effect of target distance was quantitatively assessed by subtracting gain for a target 500 cm distant from gain for a target 15 cm distant. During the period 35-45 ms after the onset of 2800 degrees/s2 head motion, only two subjects with cerebellar loss demonstrated significant VOR gain enhancement with a near target, and both of these exhibited less than half of the mean enhancement for control subjects. During the later period 125-135 ms after the onset of head rotation, when VOR gain normally depended on both target location and otolith translation, only one subject with cerebellar dysfunction consistently demonstrated gain changes in the normal direction. These findings support a role for the cerebellum in gain modulation of both the canal and otolith VOR in response to changes in distance. The short latency of gain modification suggests that the cerebellum may normally participate in target distance-related modulation of direct VOR pathways in a manner similar to that found in plasticity induced by visual-vestibular mismatch.

Otolith function in cerebellar ataxia due to mutations in the calcium channel gene CACNA1A.

The vestibulo-ocular reflexes stabilize retinal images during head movements. While there is a wealth of information about the interaction between the cerebellum and vestibulo-ocular reflexes mediated by the semicircular canals, little is known about the role of the cerebellum in the generation of the otolith-mediated linear vestibulo-ocular reflex (LVOR). By means of transient linear acceleration of the whole body along the interaural axis, we examined the LVOR in six patients with hereditary cerebellar ataxia due to mutations of the calcium channel gene CACNA1A, five with spinocerebellar ataxia type 6 (SCA6) and one with episodic ataxia type 2 (EA-2). Six age-matched normal subjects served as controls. Using a peak acceleration of 0.5 g in combination with recording by the binocular scleral magnetic search coil method, it was possible to study the latency and sensitivity of the LVOR in the first 150 ms after motion onset. The normal LVOR showed a significant dependence on viewing distance and covaried with vergence angle, and could be enhanced by the presence of a visible target. In contrast, the LVOR of ataxic patients had normal latency but significantly decreased sensitivity that was not enhanced with visible or nearer targets despite normal vergence. Substituting for the normal smooth LVOR slow phase, ataxic patients employed catch-up saccades 150-250 ms after motion onset. These findings suggest a critical role of the cerebellum in the modulation of otolith-ocular signals that is independent of motor vergence.

Vestibular function in severe bilateral vestibulopathy.

OBJECTIVES: To assess residual vestibular function in patients with severe bilateral vestibulopathy comparing low frequency sinusoidal rotation with the novel technique of random, high acceleration rotation of the whole body. METHODS: Eye movements were recorded by electro-oculography in darkness during passive, whole body sinusoidal yaw rotations at frequencies between 0.05 and 1.6 Hz in four patients who had absent caloric vestibular responses. These were compared with recordings using magnetic search coils during the first 100 ms after onset of whole body yaw rotation at peak accelerations of 2800 degrees /s(2). Off centre rotations added novel information about otolithic function. RESULTS: Sinusoidal yaw rotations at 0.05 Hz, peak velocity 240 degrees/s yielded minimal responses, with gain (eye velocity/head velocity)<0.02, but gain increased and phase decreased at frequencies between 0.2 and 1.6 Hz in a manner resembling the vestibulo-ocular reflex. By contrast, the patients had profoundly attenuated responses to both centred and eccentric high acceleration transients, representing virtually absent responses to this powerful vestibular stimulus. CONCLUSION: The analysis of the early ocular response to random, high acceleration rotation of the whole body disclosed a profound deficit of semicircular canal and otolith function in patients for whom higher frequency sinusoidal testing was only modestly abnormal. This suggests that the high frequency responses during sinusoidal rotation were of extravestibular origin. Contributions from the somatosensory or central predictor mechanisms, might account for the generation of these responses. Random, transient rotation is better suited than steady state rotation for quantifying vestibular function in vestibulopathic patients.