The horizontal vestibulo-ocular reflex during linear acceleration in the frontal plane of the cat

Summary Horizontal and vertical eye movements were recorded in alert, restrained cats that were subjected to whole-body rotations with the horizontal semicircular canals in the plane of rotation and the body centered on the axis or 45 cm eccentric from the axis of rotation. Changes in the horizontal vestibulo-ocular reflex (HVOR) due to the resultant of the linear forces (i.e., gravity and linear acceleration) acting on the otolith organs were examined during off-axis rotation when there was a centripetal acceleration along the animal's interaural axis. The HVOR time constant was slightly shortened when the resultant otolith force was not parallel to the animal's vertical axis. This effect was independent of the direction of the otolith force relative to the direction of the slow phase eye velocity. No effect on the HVOR amplitude was observed. In addition to changes in the HVOR dynamics, a significant vertical component of eye velocity was observed during stimulation of the horizontal canals when the resultant otolith force was not parallel with the animal's vertical axis. The effect was greater for larger angles between the resultant otolith force and gravity. An upward or downward component was elicited, depending on the direction of the horizontal component of eye velocity and the direction of the resultant otolith force. The vertical component was always in the direction that would tend to align the eye velocity vector with the resultant otolith force and keep the eye movement in a plane that had been rotated by the angle between the resultant otolith force and gravity.     

Low-frequency otolith and semicircular canal interactions after canal inactivation

During sustained constant velocity and low-frequency off-vertical axis rotations (OVAR), otolith signals contribute significantly to slow-phase eye velocity. The adaptive plasticity of these responses was investigated here after semicircular canal plugging. Inactivation of semicircular canals results in a highly compromised and deficient vestibulo-ocular reflex (VOR). Based on the VOR enhancement hypothesis, one could expect an adaptive increase of otolith-borne angular velocity signals due to combined otolith/canal inputs after inactivation of the semicircular canals. Contrary to expectations, however, the steady-state slow-phase velocity during constant velocity OVAR decreased in amplitude over time. A similar progressive decrease in VOR gain was also observed during low-frequency off-vertical axis oscillations. This response deterioration was present in animals with either lateral or vertical semicircular canals inactivated and was limited to the plane(s) of the plugged canals. The results are consistent with the idea that the low-frequency otolith signals do not simply enhance VOR responses. Rather, the nervous system appears to correlate vestibular sensory information from the otoliths and the semicircular canals to generate an integral response to head motion.     

Static roll and the vestibulo-ocular reflex (VOR)

Summary We measured the effect of static lateral tilt (roll) on the gain and time constant of the vestibulo-ocular reflex (VOR) in five normal subjects by recording both the horizontal and vertical components of eye velocity in space for rotation about an earth vertical axis with the head either upright or rolled to either side. The time constant of the VOR in the upright position was 19.6 ±3.2s (mean ± standard deviation). The time constant of the horizontal component with respect to the head decreased to 15.7±4.0s for 30° roll and to 12.7±2.7s for 60° roll. The time constant of the vertical component with respect to the head was 11.0±1.4 s for 30° roll and 7.5±1.6 s for 60° roll. The gain of the horizontal VOR with respect to space did not vary significantly with roll angle but a small space-vertical component to the VOR appeared during all rotations when the head was rolled away from upright. This non-compensatory nystagmus built up to a maximum of 2–3°/s at 17.0±4.7s after the onset of rotation and then decayed. These data suggest that static otolith input modulates the central storage of semicircular canal signals, and that head-horizontal and head-vertical components of the VOR can decay at different rates.     

Gravity and the vertical vestibulo-ocular reflex

Summary We studied the vertical vestibulo-ocular reflex (VOR) and vertical visual-vestibular interaction induced by voluntary pitch in the upright and onside positions in eight normal human subjects. Subjects were trained to produce sinusoidal (0.4 to 1.6 Hz) pitch head movements guided by a frequency modulated sound signal. Eye and head movements were recorded with a magnetic search coil. There was no significant difference between the pooled average gain (eye velocity/head velocity) of the vertical VOR in the upright and onside positions. Vertical VOR gain in any position could be more or less than 1.0 for individual subjects. By contrast, gain with an earth-fixed visual target was always near 1.0. Asymmetries in the gain of upward and downward VOR, pursuit and fixation suppression of the VOR were found in individual subjects, but in the group of normal subjects there was no significant difference between gain of up and down eye movements induced by vestibular, visual or visual-vestibular stimulation in any position. We conclude that during voluntary pitch otolith signals are not critical for normal functioning of the vertical VOR.     

Contribution of the maculo-ocular reflex to gaze stability in the rabbit

Summary The contribution of the maculo-ocular reflex to gaze stability was studied in 10 pigmented rabbits by rolling the animals at various angles of sagittal inclination of the rotation and/or longitudinal animal axes. At low frequencies (0.005–0.01 Hz) of sinusoidal stimulation the vestibulo-ocular reflex (VOR) was due to macular activation, while at intermediate and high frequencies it was mainly due to ampullar activation. The following results were obtained: 1) maculo-ocular reflex gain decreased as a function of the cosine of the angle between the rotation axis and the earth's horizontal plane. No change in gain was observed when longitudinal animal axis alone was inclined. 2) At 0° of rotation axis and with the animal's longitudinal axis inclination also set at 0°, the maculo-ocular reflex was oriented about 20° forward and upward with respect to the earth's vertical axis. This orientation remained constant with sagittal inclinations of the rotation and/or longitudinal animal axes ranging from approximately 5° upward to 30° downward. When the longitudinal animal axis was inclined beyond these limits, the eye trajectory tended to follow the axis inclination. In the upside down position, the maculo-ocular reflex was anticompensatory, oblique and fixed with respect to orbital coordinates. 3) Ampullo-ocular reflex gain did not change with inclinations of the rotation and/or longitudinal animal axes. The ocular responses were consistently oriented to the stimulus plane. At intermediate frequencies the eye movement trajectory was elliptic because of directional differences between the ampullo- and maculo-ocular reflexes. 4) In the upright position the coactivation of the optokinetic reflex (OKR) eliminated the eye disalignment with respect to the stimulus plane and the elliptic trajectory. 5) Combined vertical OKR and VOR gain in the prone position (VOKR + VVOR 0°) was higher than that of the combined VOKR + VVOR in the 90° nose up position. The VVOR + VOKR 90° gain was in turn higher than the VVOR + VOKR gain in the 180° upside down position. 6) We suggest that, in the dark, the maculo-ocular response tends to reduce the disalignment of both eyes with respect to the horizon rather than inducing oculocompensatory responses. In the light, this maculo-ocular reflex increases the gain of combined optokinetic and vestibular responses.     

The effect of gravity on the horizontal and vertical vestibulo-ocular reflex in the rat

Horizontal and vertical eye movements were recorded in alert pigmented rats using chronically implanted scleral search coils or temporary glue-on coils to test the dependence of the vestibulo-ocular reflex (VOR) upon rotation axis and body orientation. The contributions of semicircular-canal versus otolith-organ signals to the VOR were investigated by providing canal-only (vertical axis) and canal plus otolith (horizontal axis) stimulation conditions. Rotations that stimulated canals only (upright yaw and nose-up roll) produced an accurate VOR during middle- and high-frequency rotations (0.2-2 Hz). However, at frequencies below 0.2 Hz, the canal-only rotations elicited a phase-advanced VOR. The addition of a changing gravity stimulus, and thus dynamic otolith stimulation, to the canal signal (nose-up yaw, on-side yaw, and upright roll) produced a VOR response with accurate phase down to the lowest frequency tested (0.02 Hz). In order to further test the dependence of the VOR on gravitational signals, we tested vertical VOR with the head in an inverted posture (inverted roll). The VOR in this condition was advanced in phase across all frequencies tested. At low frequencies, the VOR during inverted roll was anticompensatory, characterized by slow-phase eye movement in the same direction as head movement. The substantial differences between canalonly VOR and canal plus otolith VOR suggest an important role of otolith organs in rat VOR. Anticompensatory VOR during inverted roll suggests that part of the otolith contribution arises from static tilt signals that are inverted when the head is inverted.     

Timing of low frequency responses of anterior and posterior canal vestibulo-ocular neurons in alert cats

The pitch vertical vestibulo-ocular reflex (VOR) is accurate and symmetrical when tested in the normal upright posture, where otolith organ and central velocity storage signals supplement the basic VOR mediated by the semicircular canals. However, when the animal and rotation axis are together repositioned by rolling 90° to one side, head forward pitch rotations that excite the anterior semicircular canals elicit a more accurately timed VOR than do oppositely directed rotations that excite the posterior canals. This suggests that velocity storage of posterior canal signals is lost when the head is placed on its side. We recorded from 47 VOR relay neurons, second-order vestibulo-ocular neurons, of alert cats to test whether asymmetries are evident in the responses of neurons in the medial and superior vestibular nuclei during earth-horizontal axis rotations in the normal upright posture. Neurons were identified by antidromic responses to oculomotor nucleus stimulation and orthodromic responses to labyrinth stimulation, and were classified as having primarily anterior, posterior, or horizontal canal input based on response directionality. Neuronal response gains and phases were recorded during 0.5 Hz and 0.05 Hz sinusoidal oscillations in darkness. During 0.5 Hz rotations, anterior canal second-order vestibulo-ocular neurons responded approximately in phase with head velocity (mean phase re head position, ±SE, 80°±3°, n=18), as did posterior canal second-order vestibulo-ocular neurons (mean phase 81°±1°, n=25). Lowering the rotation frequency to 0.05 Hz resulted in only slight advances in response phases of individual anterior canal second-order vestibulo-ocular neurons (mean phase 86°±6°, mean advance 7°±5°, n=12). In contrast, posterior canal second-order vestibulo-ocular neurons behaved more like semicircular canal afferents, with responses markedly phase-advanced (mean advance 28°±5°, n=14) by lowering rotation frequency to 0.05 Hz (mean phase 111°±5°, n=14). In summary, low frequency responses of anterior and posterior canal second-order vestibulo-ocular neurons recorded during horizontal axis pitch correspond to the VOR they excite during vertical axis pitch. These results show that velocity storage is evident at anterior but not posterior canal second-order vestibulo-ocular neurons. We conclude that responses of posterior canal second-order vestibulo-ocular neurons are insufficient to explain the accurate low frequency VOR phase observed during backward head pitch in the upright posture, and that velocity storage or otolith signals required for VOR accuracy are carried by other neurons. Electronic Publication     

Acute adaptation of the vestibuloocular reflex: signal processing by floccular and ventral parafloccular Purkinje cells

The gain of the vertical vestibuloocular reflex (VVOR), defined as eye velocity/head velocity was adapted in squirrel monkeys by employing visual-vestibular mismatch stimuli. VVOR gain, measured in the dark, could be trained to values between 0.4 and 1.5. Single-unit activity of vertical zone Purkinje cells was recorded from the flocculus and ventral paraflocculus in alert squirrel monkeys before and during the gain change training. Our goal was to evaluate the site(s) of learning of the gain change. To aid in the evaluation, a model of the vertical optokinetic reflex (VOKR) and VVOR was constructed consisting of floccular and nonfloccular systems divided into subsystems based on the known anatomy and input and output parameters. Three kinds of input to floccular Purkinje cells via mossy fibers were explicitly described, namely vestibular, visual (retinal slip), and efference copy of eye movement. The characteristics of each subsystem (gain and phase) were identified at different VOR gains by reconstructing single-unit activity of Purkinje cells during VOKR and VVOR with multiple linear regression models consisting of sensory input and motor output signals. Model adequacy was checked by evaluating the residual following the regressions and by predicting Purkinje cells' activity during visual-vestibular mismatch paradigms. As a result, parallel changes in identified characteristics with VVOR adaptation were found in the prefloccular/floccular subsystem that conveys vestibular signals and in the nonfloccular subsystem that conveys vestibular signals, while no change was found in other subsystems, namely prefloccular/floccular subsystems conveying efference copy or visual signals, nonfloccular subsystem conveying visual signals, and postfloccular subsystem transforming Purkinje cell activity to eye movements. The result suggests multiple sites for VVOR motor learning including both flocculus and nonflocculus pathways. The gain change in the nonfloccular vestibular subsystem was in the correct direction to cause VOR gain adaptation while the change in the prefloccular/floccular vestibular subsystem was incorrect (anti-compensatory). This apparent incorrect directional change might serve to prevent instability of the VOR caused by positive feedback via the efference copy pathway.     

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. Received: 1 April 1996 / Accepted: 15 October 1996     

Asymmetric short-term adaptation of the vertical vestibulo-ocular reflex in humans

Anatomical and electrophysiological studies have demonstrated up–down asymmetries in vertical ocular motor pathways. We investigated whether these asymmetries extend to the capacity for short-term adaptation of the vertical vestibulo-ocular reflex (VVOR) in humans. Specifically, we asked whether smooth pursuit signals are sufficient to asymmetrically adapt the VVOR. Healthy human subjects (N=8), positioned 90° left-ear-down and fixating with their eyes upon a small laser dot (diameter: 0.1°) projected on a sphere (distance: 1.4 m) were trained toward low VVOR gain for 30 min with symmetric and asymmetric visual VVOR cancellation paradigms, while being oscillated (0.2 Hz, ±20°) on a motorized turntable about the interaural earth-vertical axis. During asymmetric VVOR cancellation, the target was head-fixed in either the pitch-up or pitch-down half-cycles of oscillation (=trained direction) and space-fixed during the other half-cycles (=untrained direction). During symmetric VVOR cancellation, the target was head-fixed throughout the oscillations. Before and after adaptation, the pitch-up and pitch-down VOR gains were assessed during turntable oscillation in complete darkness. Before adaptation, average gains of pitch-up (0.75±0.15 SD) and pitch-down (0.79±0.19 SD) VOR were not significantly different (paired t test: P>0.05). On an average, relative gain reductions induced by selective pitch-up (pitch-up VOR: 32%; pitch-down VOR: 21%) and pitch-down (pitch-up VOR: 18%; pitch-down VOR: 30%) VOR cancellation were significantly (P<0.05) larger in the trained than in the untrained direction. Symmetric visual VVOR cancellation led to a significantly (P<0.01) larger relative gain reduction of the pitch-down (41%) than the pitch-up (33%) VOR. None of the paradigms led to significant changes of phase or offset. We conclude that, in human subjects, the smooth pursuit system is capable to asymmetrically decrease the gain of the VVOR equally well in both the upward and downward direction. The unexpected asymmetric decrease of the VVOR gain after symmetric visual cancellation may be related to the directional preferences of vertical gaze–velocity sensitive Purkinje cells in the flocculus for the downward direction.This work was supported by Swiss National Science Foundation (3231-051938.97/31-63465.00/#3200BO-1054534), and Betty and David Koetser Foundation for Brain Research (Zurich, Switzerland).     

Effect of viewing distance and location of the axis of head rotation on the monkey's vestibuloocular reflex. I. Eye movement responses.

1. The vestibuloocular reflex (VOR) stabilizes images on the retina against movements of the head in space. Viewing distance, target eccentricity, and location of the axis of rotation may influence VOR responses because rotation of the head about most axes in space rotates and translates the eyes relative to visual targets. To study the VOR response to combined rotation and translation, monkeys were placed on a rate table and rotated briefly in the dark about a vertical axis that was located in front of or behind the eyes. The monkeys fixated a near or far visual target that was extinguished before the rotation. Eye movements were recorded from both eyes by the use of the search coil technique. 2. Peak eye velocity evoked by the VOR was linearly related to vergence angle for any axis of rotation. The percent change in the VOR with near target viewing relative to far target viewing at a vergence angle of 20 degrees was linearly related to the location of the axis of rotation. Axes located behind the eyes produced positive changes in VOR amplitude, and axes located in front of the eyes produced negative changes in VOR amplitude. An axis of rotation located in the coronal plane containing the centers of rotation of the eyes produced no modification of VOR amplitude. For any axis, the VOR compensated for approximately 90% of the translation of the eye relative to near targets. 3. The initial VOR response was not correct in magnitude but was refined by a series of three temporally delayed corrections of increasing complexity. The earliest VOR-evoked eye movement (10-20 ms after rotation onset) was independent of viewing distance and rotational axis location. In the next 100 ms, eye speed appeared to be sequentially modified three times: within 20 ms by viewing distance; within 30 ms by otolith translation; and within 100 ms by eye translation relative to the visual target. 4. These data suggest a formal model of the VOR consisting of four channels. Channel 1 conveys an unmodified head rotation signal with a pure delay of 10 ms. Channel 2 conveys an angular head velocity signal, modified by viewing distance with a pure delay of 20 ms, but invariant with respect to the location of the axis of rotation. Channel 3 conveys a linear head velocity signal, dependent on the location of the axis of rotation, that is modified by viewing distance with a pure delay of 30 ms.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influence of eye and head position on the vestibulo-ocular reflex

Summary For the vestibulo-ocular reflex (VOR) to function properly, namely to ensure a stable retinal image under all circumstances, it should be able to take into account varying eye positions in the orbit and varying orientations of the head with respect to the axis about which it is rotating. We tested this capability by quantifying the gain and the time constant of the horizontal component of the VOR during rotation about an earth vertical axis when the line of sight (optical axis) was moved out of the plane of head rotation — either by rotating the eyes up or down in the orbit or by pitching the head up or down with respect to earth-horizontal. In either case the gain of the horizontal component of the VOR was attenuated precisely by the cosine of the angle made between the optical axis and the plane of head rotation. Furthermore, if the head was pitched up or down but the eye rotated oppositely in the orbit so as to keep the line of sight in the plane of head rotation the gain of the horizontal component of the VOR was the same value as with the head and eyes both straight ahead. In contrast, the time constant of the VOR varied only as a function of the orientation of the head and not as a function of eye position in the orbit. During rotation about an earth vertical axis, the time constant was longest (about 18 s) when the head was pitched forward to place the lateral canals near earth-horizontal and shortest (about 11 s) when the head was pitched backward to place the vertical canals near earth-horizontal. Finally, since during rotation in yaw the pattern of stimulation of the lateral and vertical semicircular canals varies with different head orientations one can use measurements of the horizontal component of the VOR, under varying degrees of pitch of the head, to calculate the relative ability of the lateral and vertical semicircular canals to transduce head velocity.Dr. Fetter is a visiting scientist from the Neurologische Universitätsklinik, Eberhard-Karls-Universität, Liebermeisterstr. 18-20, D-7400 Tübingen, Federal Republic of Germany     

Absence of vestibular habituation of the vestibulo-ocular reflex in the vertical plane in the cat

 The effect of exposure to repeated angular velocity steps about the earth-vertical axis on the vertical vestibulo-ocular reflex (VOR) during onside pitch rotation was investigated in normal cats. By contrast with the VOR in the horizontal plane, the amplitude and duration of the vertical VOR did not progressively decrease throughout the repetition of velocity steps alternated in both directions. Instead, the amplitude of VOR decreased by about 40% during the very first trials in naive cats and then stayed unchanged with repeated stimuli. Habituation of the amplitude of the vertical VOR was observed when the velocity steps were always directed in the same direction. However, the duration of the vertical VOR did not show any signs of habituation. The habituation of the amplitude of the vertical VOR during unidirectional training was due to the progressive development of an initial inhibition of the VOR. This initial inhibition appeared much earlier during the bidirectional protocol, and was presumably responsible for the larger reduction in VOR amplitude observed during the very first session. These results support the model of two distinct mechanisms for VOR habituation, one producing an increasing inhibition of nystagmus, and the other depressing the response duration, and suggest that only the first mechanism is generated during repeated stimulation in the vertical plane. The low-frequency information provided by the velocity storage mechanism during onside pitch rotation, when the otoliths are positioned so they do not signal head tilt relative to gravity, could prevent a decrease in the overall response by the second mechanism. Received: 25 March 1996 / Accepted: 29 January 1997     

A longitudinal study of oculomotor function in normal older people

Cross-sectional studies have found declines in most measures of oculomotor function in older subjects compared to young controls, but no prior study has followed the same subjects over time. We measured saccade peak velocity, saccade delay time, smooth pursuit, optokinetic nystagmus (OKN), visual-vestibular-ocular-reflex (VVOR), fixation suppression of the vestibulo-ocular reflex (VOR-fix), and the vestibulo-ocular reflex in 53 subjects (older than 75 years) able to complete at least 9 yearly evaluations. In addition at each visit all patients underwent a complete history and examination, a gait and balance assessment, mini-mental status evaluation, and visual acuity testing. A subset of subjects completed 12 yearly evaluations (14 patients). Despite significant declines of most variables over time, smooth pursuit gain and saccade peak velocity remained stable during the duration of the study both in the 9-year group and the patients completing 12 years. Decline in OKN, VVOR, and VOR were significantly correlated (P<0.001) with decline in the Tinetti gait and balance score, even after controlling for age. In normal healthy older subjects, smooth pursuit and saccade peak velocity are relatively maintained while OKN, VVOR, and VOR function decline. The significant correlation between decline in oculomotor measures and gait and balance measures (even after controlling for age) suggests a common mechanism for the decline in both measures.     

Deficits in vertical and torsional eye movements after uni- and bilateral muscimol inactivation of the interstitial nucleus of Cajal of the alert monkey

The mesencephalic interstitial nucleus of Cajal (iC) is considered the neural integrator for vertical and torsional eye movements and has also been proposed to be involved in saccade generation. The aim of this study was to elucidate the function of iC in neural integration of different types of eye movements and to distinguish eye movement deficits due to iC impairment from that of the immediately adjacent rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). We addressed the following questions: (1) According to the neural integrator hypothesis, all eye movements including the saccadic system and the vestibulo-ocular reflex (VOR) share a common neural integrator. Do iC lesions impair gaze-holding function for vertical and torsional eye positions and the torsional and vertical VOR gain to a similar degree? (2) What are the dynamic properties of vertical and torsional eye movements deficits after iC lesions, e.g., the specificity of torsional and vertical nystagmus? (3) Is iC involved in saccade generation? We performed 13 uni- and three bilateral iC inactivations by muscimol microinjections in four alert monkeys. Three-dimensional eye movements were studied under head-stationary conditions during vertical and torsional VOR. Under static conditions, unilateral iC injections evoked a shift of Listing’s plane to the contralesional side (up to 20°), which increased (ipsilesional ear down) or decreased (ipsilesional ear up) by additional static vestibular stimulation in the roll plane, i.e., ocular counterroll was preserved. The monkeys showed a spontaneous torsional nystagmus with a profound downbeat component. The fast phases of torsional nystagmus always beat toward the lesion side (ipsilesional). Pronounced gaze-holding deficit for torsional and vertical eye positions (neural integrator failure) was reflected by the reduction of time constants of the exponential decay of the slow phase to 330–370 ms. Whereas the vertical oculomotor range was profoundly decreased (up to 50%) and vertical saccades were reduced in amplitude, saccade velocity remained normal and horizontal eye movements were not affected. Bilateral iC injections reduced the shift of Listing’s plane caused by unilateral injections, i.e., back toward the plane of zero torsion. Torsional nystagmus reversed its direction and ceased, whereas vertical nystagmus persisted. In contrast to unilateral injection, there was additional upbeating nystagmus. Time constants of the position integrator of the gaze-holding system did not differ between unilateral and bilateral injections. The range of stable vertical eye positions and saccade amplitude was smaller when compared with unilateral injections, but the main sequence remained normal. Dynamic vestibular stimulation after unilateral iC injections had virtually no effect on torsional and vertical VOR gain and phase at the same time when time constants already indicated severe integrator failure. Torsional VOR elicited a constant slow-phase velocity offset up to 30° toward the contralesional side, i.e., in the opposite direction to spontaneous torsional nystagmus. Likewise, vertical VOR showed a velocity offset in an upward direction, i.e., opposite to the spontaneous downbeat nystagmus. Contralesional torsional and upward vertical quick phases were missing or severely reduced in amplitude but showed normal velocity. In contrast, bilateral iC injections reduced the gain of the torsional and vertical VOR by 50% and caused a phase lead of 10–20° (eye compared with head velocity). We propose that the slow-phase velocity offset during torsional and vertical VOR reflects a vestibular imbalance. It therefore appears likely that the vertical and torsional nystagmus after iC lesions is not only caused by a neural integrator failure but also by a vestibular imbalance. Unilateral iC injections have clearly differential effects on the VOR and the gaze-holding function. These results are not compatible with a single common neural integrator model, which would predict a much stronger VOR gain reduction and phase advance, as found in our data. Our data support the existence of multiple integrators in iC with parallel processing.     

Horizontal vestibuloocular reflex (VOR) head velocity estimation in Purkinje cell degeneration (pcd/pcd) mutant mice

The horizontal vestibuloocular reflex (VOR) of Purkinje cell degeneration (pcd/pcd) mutant mice, which lack a functional cerebellar cortex, was compared in darkness to that of wild-type animals during constant velocity yaw rotations about an earth-horizontal axis and during sinusoidal yaw rotations about an earth-vertical axis. Both wild-type and pcd/pcd mice showed a compensatory average VOR eye velocity, or bias, during constant velocity horizontal axis rotations, evidence of central neural processing of otolith afferent signals to create a signal proportional to head angular velocity. Eye velocity bias was greater in pcd/pcd mice than in wild-type mice at a low rotational velocity (32 degrees/s), but less at higher velocities (128 and 200 degrees/s). Lesion of the medial nodulus severely attenuated eye velocity bias in two wild-type mice, without attenuating VOR during sinusoidal vertical axis yaw rotations at 0.2 Hz. These results show that while head velocity estimation in mice, as in primates, depends on the cerebellum, pcd/pcd mutant mice develop velocity estimation without a functional cerebellar cortex. We conclude that neural circuits that exclude cerebellar cortex are capable of the signal processing necessary for head angular velocity estimation, but that these circuits are insufficient for normal estimation at high velocities.     

The human vertical vestibulo-ocular reflex during combined linear and angular acceleration with near-target fixation

The purpose of this study was to examine the effect of fixation target distance on the human vestibuloocular reflex (VOR) during eccentric rotation in pitch. Such rotation induces both angular and linear acceleration. Eight normal subjects viewed earth-fixed targets that were either remote or near to the eyes during wholebody rotation about an earth-horizontal axis that was either oculocentric or 15 cm posterior (eccentric) to the eyes. Eye and head movements were recorded using magnetic search coils. Using a servomotor-driven chair, passive whole-body rotations were delivered as trains of single-frequency sinusoids at frequencies from 0.8 to 2.0 Hz and as pseudorandom impulses of acceleration. In the light, the visually enhanced VOR (VVOR) was recorded while subjects were asked to fixate targets at one of several distances. In darkness, subjects were asked to remember targets that had been viewed immediately prior to the rotation. In order to eliminate slip of the retinal image of a near target when the axis of rotation of the head is posterior to the eyes, the ideal gain (compensatory eye velocity divided by head velocity) of the VVOR and VOR must exceed 1.0. Both the VOR and VVOR were found to have significantly enhanced gains during sinusoidal and pseudorandom impulses of rotation (P<0.05). Enhancement of VVOR gain was greatest at low frequencies of head rotation and decreased with increasing frequency. However, enhanced VOR gain only slightly exceeded 1.0, and VVOR gain enhancement was significantly lower than the expected ideal values for the stimulus conditions employed (P<0.05). During oculocentric rotations with near targets, both the VOR and VVOR tended to exhibit small phase leads that increased with rotational frequency. In contrast, during eccentric rotations with near targets, there were small phase lags that increased with frequency. Visual tracking contributes during ocular compensatory responses to sustained head rotation, although the latency of visual tracking reflexes exceeds 100 ms. In order to study initial vestibular responses prior to modification by visual tracking, we presented impulses of head acceleration in pseudorandom sequence of initial positions and directions, and evaluated the ocular response in the epoch from 25 to 80 ms after movement onset. As with sinusoidal rotations, pseudorandom eccentric head rotation in the presence of a near, earth-fixed target was associated with enhancement of VVOR and VOR gains in the interval from 25 to 80 ms from movement onset. Despite the inability of visual tracking to contribute to these responses, VVOR gain significantly exceeded VOR gain for pseudorandom accelerations. This gain enhancement indicates that target distance and linear motion of the head are considered by the human ocular motor system in adjustment of performance of the early VOR, prior to a contribution by visual following reflexes. Vergence was appropriate to target distance during all VVOR rotations, but varied during VOR rotations with remembered targets. For the 3-m target distance, vergence during the VOR was stable over each entire trial but slightly exceeded the ideal value. For the 0.1-m near target, instantaneous vergence during the VOR typically declined gradually in a manner not corresponding to the time course of instantaneous VOR gain change; mean vergence over entire trials ranged from 60 to 90% of ideal, corresponding to target distances for which ideal gain would be much higher than actually observed. These findings suggest a dissociation between vergence and VOR gain during eccentric rotation with near targets in the frequency range from 0.8 to 2.0 Hz.     

The three-dimensional vestibulo-ocular reflex during prolonged microgravity

Single-case, longitudinal studies of the three-dimensional vestibulo-ocular response (VOR) were conducted with two spaceflight subjects over a 180-day mission. For reference, a control study was performed in the laboratory with 13 healthy volunteers. Horizontal, vertical and torsional VOR was measured during active yaw, pitch and roll oscillations of the head, performed during visual fixation of real and imaginary targets. The control group was tested in the head-upright position, and in the gravity-neutral, onside and supine positions. Binocular eye movements were recorded throughout using videooculography, yielding eye position in Fick co-ordinates. Eye velocity was calculated using quaternion algebra. Head angular velocities were measured by a head-mounted rate sensor. Eye/head velocity gain and phase were evaluated for the horizontal, vertical and torsional VOR. The inclination of Listing's plane was also calculated for each test session. Control group gain for horizontal and vertical VOR was distributed closely around unity during real-target fixation, and reduced by 30-50% during imaginary-target trials. Phase was near zero throughout. During head pitch in the onside position, vertical VOR gain did not change significantly. Analysis of up/down asymmetry indicated that vertical VOR gain for downward head movement was significantly higher than for upward head movement. Average torsional VOR gain with real-target fixation was significantly higher than with imaginary-target fixation. No difference in phase was found. In contrast to vertical VOR gain, torsional VOR gain was significantly lower in the gravity-neutral supine position. Spaceflight subjects showed no notable modification of horizontal or vertical VOR gain or phase during real-target fixation over the course of the mission. However, the up/down asymmetry of vertical VOR gain was inverted in microgravity. Torsional VOR gain was clearly reduced in microgravity, with some recovery in the later phase. After landing, there was a dip in gain during the first 24 h, with subsequent recovery to near baseline over the 13-day period tested. Listing's plane appeared to remain stable throughout the mission. The findings reflect various functions of the otolith responses. The reduced torsional VOR gain in microgravity is attributed to the absence of the gravity-dependent, dynamic stimulation to the otoliths (primarily utricles). On the other hand, the reversal of vertical VOR up/down gain asymmetry in microgravity is attributed to the off-loading of the constant 1-g bias (primarily to the saccules) on Earth. The observed increase in torsional VOR gain from the 1st to the 6th month in microgravity demonstrates the existence of longer-term adaptive processes than have previously been considered. Likely factors are the adaptive reweighting of neck-proprioceptive afferents and/or enhancement of efference copy.     

Neural processing of gravito-inertial cues in humans. I. Influence of the semicircular canals following post-rotatory tilt

Sensory systems often provide ambiguous information. Integration of various sensory cues is required for the CNS to resolve sensory ambiguity and elicit appropriate responses. The vestibular system includes two types of sensors: the semicircular canals, which measure head rotation, and the otolith organs, which measure gravito-inertial force (GIF), the sum of gravitational force and inertial force due to linear acceleration. According to Einstein's equivalence principle, gravitational force is indistinguishable from inertial force due to linear acceleration. As a consequence, otolith measurements must be supplemented with other sensory information for the CNS to distinguish tilt from translation. The GIF resolution hypothesis states that the CNS estimates gravity and linear acceleration, so that the difference between estimates of gravity and linear acceleration matches the measured GIF. Both otolith and semicircular canal cues influence this estimation of gravity and linear acceleration. The GIF resolution hypothesis predicts that inaccurate estimates of both gravity and linear acceleration can occur due to central interactions of sensory cues. The existence of specific patterns of vestibuloocular reflexes (VOR) related to these inaccurate estimates can be used to test the GIF resolution hypothesis. To investigate this hypothesis, we measured eye movements during two different protocols. In one experiment, eight subjects were rotated at a constant velocity about an earth-vertical axis and then tilted 90 degrees in darkness to one of eight different evenly spaced final orientations, a so-called "dumping" protocol. Three speeds (200, 100, and 50 degrees /s) and two directions, clockwise (CW) and counterclockwise (CCW), of rotation were tested. In another experiment, four subjects were rotated at a constant velocity (200 degrees /s, CW and CCW) about an earth-horizontal axis and stopped in two different final orientations (nose-up and nose-down), a so-called "barbecue" protocol. The GIF resolution hypothesis predicts that post-rotatory horizontal VOR eye movements for both protocols should include an "induced" VOR component, compensatory to an interaural estimate of linear acceleration, even though no true interaural linear acceleration is present. The GIF resolution hypothesis accurately predicted VOR and induced VOR dependence on rotation direction, rotation speed, and head orientation. Alternative hypotheses stating that frequency segregation may discriminate tilt from translation or that the post-rotatory VOR time constant is dependent on head orientation with respect to the GIF direction did not predict the observed VOR for either experimental protocol.     

Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum

Summary We habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore ×2.2 magnifying or ×0.5 reducing lenses. Adaptation occurred rapidly and reached about ±30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6–8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h ₀). Nodulouvulectomy, which reversed habituation, would be effected by decreasing h ₀, thereby increasing the VOR time constant. Small values of h ₀ would cause velocity storage to approach an ideal integrative process, leading the system to become unstable. By controlling the VOR time constant through habituation, the nodulus and uvula can stabilize the slow component of the VOR. VOR gain adaptation was related to a modification of the direct vestibular path gain g ₁, without altering the coupling to velocity storage g ₀ or its time constant (1/h ₀). The mismatched direct- and indirect-pathway gains simulated the overshoots in the dynamic response to a step in velocity, that were observed experimentally. We conclude that independent distributed elements in the VOR modify its dynamic response, under control of separate parts of the vestibulocerebellum.