Impairments in the initial horizontal vestibulo-ocular reflex of older humans

To determine age-related changes, the initial horizontal vestibulo-ocular reflex (VOR) of 11 younger normal subjects (aged 20–32 years) was compared with that of 12 older subjects (aged 58–69 years) in response to random transients of whole-body acceleration of 1,000 and 2,800°/s² delivered around eccentric vertical axes ranging from 10 cm anterior to 20 cm posterior to the eyes. Eye and head positions were sampled at 1,200 Hz using magnetic search coils. Subjects fixed targets 500 cm or 15 cm distant immediately before the unpredictable onset of rotation in darkness. For all testing conditions, younger subjects exhibited compensatory VOR slow phases with early gain (eye velocity/head velocity, interval 35–45 ms from onset of rotation) of 0.90±0.02 (mean ± SEM) for the higher head acceleration, and 0.79±0.02 for the lower acceleration. Older subjects had significantly (P<0.0001) lower early gain of 0.77±0.04 for the higher head acceleration and 0.70±0.02 for the lower acceleration. Late gain (125–135 ms from onset of rotation) was similar for the higher and lower head accelerations in younger subjects. Older subjects had significantly lower late gain at the higher head acceleration, but gain similar to the younger subjects at the lower acceleration. All younger subjects maintained slow-phase VOR eye velocity to values ≥200°/s throughout the 250-ms rotation, but, after an average of 120 ms rotation (mean eccentricity 13°), 8 older subjects consistently had abrupt declines (ADs) in slow-phase VOR velocity to 0°/s or even the anticompensatory direction. These ADs were failures of the VOR slow phase rather than saccades and were more frequent with the near target at the higher acceleration. Slow-phase latencies were 14.4±0.4 ms and 16.8±0.4 ms for older subjects at the higher and lower accelerations, significantly longer than comparable latencies of 10.0±0.5 ms and 12.0±0.6 ms for younger subjects. Late VOR gain modulation with target distance was significantly attenuated in older subjects only for the higher head acceleration. Electronic Publication     

Effect of unilateral vestibular deafferentation on the initial human vestibulo-ocular reflex to surge translation

Transient whole-body surge (fore-aft) translation at 0.5 G peak acceleration was administered to six subjects with unilateral vestibular deafferentation (UVD), and eight age-matched controls. Subjects viewed eccentric targets to determine if linear vestibulo-ocular reflex (LVOR) asymmetry might lateralize otolith deficits. Eye rotation was measured using magnetic search coils. Immediately before surge, subjects viewed a luminous target 50 cm away, centered or displaced 10° horizontally or vertically. The target was extinguished during randomly directed surges. LVOR gain relative to ideal velocity in subjects with UVD for the contralesional horizontally eccentric target (0.59 ± 0.08, mean ± SEM) did not differ significantly from normal (0.50 ± 0.04), but gain for the ipsilesional eccentric target (0.35 ± 0.02) was significantly less than normal (0.48 ± 0.03, P < 0.05). Normal subjects had mean gain asymmetry for horizontally eccentric targets of 0.17 ± 0.03, but asymmetry in UVD was significantly increased to 0.35 ± 0.05 (P < 0.05). Four of six subjects with UVD had maximum gain asymmetry outside normal 95% confidence limits. Asymmetry did not correlate with UVD duration. Gain for 10° vertically eccentric targets averaged 0.38 ± 0.14 for subjects with UVD, insignificantly lower than the normal value of 0.75 ± 0.15 (P > 0.05). Surge LVOR latency was symmetrical in UVD, and did not differ significantly from normal. There was no significant difference in response between dark and visible target conditions until 200 ms after surge onset. Chronic human UVD, on average, significantly impairs the surge LVOR for horizontally eccentric targets placed ipsilesionally, but this asymmetry is small relative to interindividual variation. Grant Support: United States Public Health Service grants DC02952 and AG09693. JLD was recipient of an Unrestricted Award from Research to Prevent Blindness and is Leonard Apt Professor of Ophthalmology.     

Three dimensional kinematics of rapid compensatory eye movements in humans with unilateral vestibular deafferentation

Saccades executed with the head stationary have kinematics conforming to Listing’s law (LL), confining the ocular rotational axis to Listing’s plane (LP). In unilateral vestibular deafferentation (UVD), the vestibulo-ocular reflex (VOR), which does not obey LL, has at high head acceleration a slow phase that has severely reduced velocity during ipsilesional rotation, and mildly reduced velocity during contralesional rotation. Studying four subjects with chronic UVD using 3D magnetic search coils, we investigated kinematics of stereotypic rapid eye movements that supplement the impaired VOR. We defined LP with the head immobile, and expressed eye and head movements as quaternions in LP coordinates. Subjects underwent transient whole body yaw at peak acceleration 2,800°/s² while fixating targets centered, or 20° up or down prior to rotation. The VOR shifted ocular torsion out of LP. Vestibular catch-up saccades (VCUS) occurred with mean latency 90 ± 44 ms (SD) from ipsilesional rotation onset, maintained initial non-LL torsion so that their quaternion trajectories paralleled LP, and had velocity axes changing by half of eye position. During contralesional rotation, rapid eye movements occurred at mean latency 135 ± 36 ms that were associated with abrupt decelerations (ADs) of the horizontal slow phase correcting 3D deviations in its velocity axis, with quaternion trajectories not paralleling LP. Rapid eye movements compensating for UVD have two distinct kinematics. VCUS have velocity axis dependence on eye position consistent with LL, so are probably programmed in 2D by neural circuits subserving visual saccades. ADs have kinematics that neither conform to LL nor match the VOR axis, but appear instead programmed in 3D to correct VOR axis errors. United States Public Health Service grants DC-005224. Joseph L. Demer is Leonard Apt Professor of Ophthalmology. Benjamin T. Crane was supported by a grant from the Giannini Family Foundation.     

Interaction between otolith organ and semicircular canal vestibulo-ocular reflexes during eccentric rotation in humans

Controversy remains about the linearity of the interaction between horizontal semicircular canal and otolith organ vestibulo-ocular reflexes (VORs) in the generation of horizontal eye movements during head movements including both rotational and translational components. We used three eccentric rotation techniques to investigate this interaction in human subjects: (1) the tangential interaural acceleration was varied using three head positions (on-axis, 25 and 40 cm ahead of the rotational axis), while angular head velocity remained unchanged; (2) the magnitude of the angular head velocity was varied with head eccentricity to keep the tangential interaural acceleration unchanged; (3) the subject’s head was oriented either upright or 90° forward from upright (nose-down). Experiments were performed in complete darkness with the subjects remembering a close earth-fixed target (20 cm distant) while being rotated at 1.2 and 1.8 Hz. Our data showed that the translational component of the VOR evoked during eccentric yaw rotation increased proportionally with an increase in head eccentricity, i.e. with tangential acceleration. We also found that the translational component of the VOR was equal for motion stimuli producing identical interaural tangential accelerations even when angular velocities differed. In addition, we found that the translational component of the VOR evoked during head upright eccentric rotation was equal to the translational VOR evoked during nose-down rotation for a given stimulus and head eccentricity. We conclude that these three findings are in agreement with what would be expected from a linear interaction (i.e. algebraic summation) between otolith organ and horizontal canal VORs for the generation of horizontal compensatory eye movements during head motion.

The dynamics of the vestibulo-ocular reflex after peripheral vestibular damage I. Frequency-dependent asymmetry

 Accurate performance by the vestibulo-ocular reflex (VOR) is necessary to stabilize visual fixation during head movements. VOR performance is severely affected by peripheral vestibular damage; after one horizontal semicircular canal is plugged, the horizontal VOR is asymmetric and its amplitude is reduced. The VOR recovers partially. We investigated the limits of recovery by measuring the VOR’s response to ipsilesional and contralesional rotation after unilateral peripheral damage in cats. We found that the VOR’s response to rotation at high frequencies remained asymmetric after recovery was complete. When the stimulus was a pulse of head velocity comprising a dynamic overshoot followed by a plateau, gain was partially restored and symmetry completely restored within 30 days after the plug, but only for the plateau response. The overshoot in eye velocity remained asymmetric. The asymmetry was independent of stimulus velocity throughout the known linear velocity range of primary vestibular afferents. Sinusoidal rotation at 0.05–8 Hz revealed that, within this range, the persistent asymmetry was significant only at frequencies above 2 Hz. Asymmetry was independent of the peak head acceleration over the range of 50–500°/s². When both horizontal canals were plugged, a small residual VOR was observed, suggesting residual signal transduction by plugged semicircular canals. However, transduction by plugged canals could not explain the enhancement of the VOR gain, at high frequencies, for rotation away from the plugged side compared with rotation toward the plug. Also, the high-frequency asymmetry was present after recovery from a unilateral labyrinthectomy. These results suggest that high-frequency asymmetry after unilateral damage is not due to residual function in the plugged canal. The findings are discussed in the context of a bilateral model of the VOR that includes central filtering. Received: 21 January 1998 / Accepted: 1 October 1998     

Vestibular perception and action employ qualitatively different mechanisms. II. VOR and perceptual responses during combined Tilt&Translation

To compare and contrast the neural mechanisms that contribute to vestibular perception and action, we measured vestibuloocular reflexes (VOR) and perceptions of tilt and translation. We took advantage of the well-known ambiguity that the otolith organs respond to both linear acceleration and tilt with respect to gravity and investigated the mechanisms by which this ambiguity is resolved. A new motion paradigm that combined roll tilt with inter-aural translation ("Tilt&Translation") was used; subjects were sinusoidally (0.8 Hz) roll tilted but with their ears above or below the rotation axis. This paradigm provided sinusoidal roll canal cues that were the same across trials while providing otolith cues that varied linearly with ear position relative to the earth-horizontal rotation axis. We found that perceived tilt and translation depended on canal cues, with substantial roll tilt and inter-aural translation perceptions reported even when the otolith organs measured no inter-aural force. These findings match internal model predictions that rotational cues from the canals influence the neural processing of otolith cues. We also found horizontal translational VORs that varied linearly with radius; a minimal response was measured when the otolith organs transduced little or no inter-aural force. Hence, the horizontal translational VOR was dependent on otolith cues but independent of canal cues. These findings match predictions that translational VORs are elicited by simple filtering of otolith signals. We conclude that internal models govern human perception of tilt and translation at 0.8 Hz and that high-pass filtering governs the human translational VOR at this same frequency.     

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. II. Responses after canal plugging.

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1-4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3, 000 degrees /s(2), peak velocity = 150 degrees /s) was 0.61 +/- 0.14 (mean +/- SD) for contralesional rotations and 0.33 +/- 0.03 for ipsilesional rotations. Within 18-24 h after animals were returned to light, the VOR gain for contralesional rotations increased to 0. 88 +/- 0.05, whereas there was only a slight increase in the gain for ipsilesional rotations to 0.37 +/- 0.07. A symmetrical increase in the gain measured at the plateau of head velocity was noted after animals were returned to light. The latency of the VOR was 8.2 +/- 0. 4 ms for ipsilesional and 7.1 +/- 0.3 ms for contralesional rotations. The VOR evoked by sinusoidal rotations of 0.5-15 Hz, +/-20 degrees /s had no significant half-cycle asymmetries. The recovery of gain for these responses after plugging was greater at lower than at higher frequencies. Responses to rotations at higher velocities for frequencies >/=4 Hz showed an increase in contralesional half-cycle gain, whereas ipsilesional half-cycle gain was unchanged. A residual response that appeared to be canal and not otolith mediated was noted after plugging of all six semicircular canals. This response increased with frequency to reach a gain of 0.23 +/- 0.03 at 15 Hz, resembling that predicted based on a reduction of the dominant time constant of the canal to 32 ms after plugging. A model incorporating linear and nonlinear pathways was used to simulate the data. The coefficients of this model were determined from data in animals with intact vestibular function. Selective increases in the gain for the linear and nonlinear pathways predicted the changes in recovery observed after canal plugging. An increase in gain of the linear pathway accounted for the recovery in VOR gain for both responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the gain of the nonlinear pathway. This pathway was driven into inhibitory cutoff at low velocities and therefore made no contribution for rotations toward the ipsilesional side.     

The squirrel monkey vestibulo-ocular reflex and adaptive plasticity in yaw,pitch, and roll

Summary The vestibulo-ocular reflex (VOR) was studied in adult squirrel monkeys before and after adaptation to magnifying and minifying viewing conditions. Monkeys were subjected to broadband (0.05–0.71 Hz) conditioning rotation for six hours in head yaw, pitch, and roll on separate occasions, and the VORs in these three planes were studied in darkness to assess adaptive plasticity in the reflexes. The gain of the horizontal VOR (H-VOR) averaged 0.8 across the frequency bandwidth studied (0.025–4 Hz). Phase was near 0° from 4 to around 0.1 Hz, but developed a progressive lead as frequency declined further. Normal vertical VOR (V-VOR) gain climbed from 0.6 at 0.025 Hz to near 1 as frequency increased to 4 Hz. Phase lead was more pronounced at low frequencies than in the H-VOR. The normal torsional VOR (T-VOR) qualitatively resembled the V-VOR, showing similar phase but lower gains (0.3–0.7) across the frequency bandwidth. These findings suggest that the dynamics of the V-VOR and T-VOR resemble canal characteristics more closely than does the H-VOR. After adaptation to visual minification and conditioning rotation (0.5X for yaw and pitch, 0X for roll), gain decreased in each of the planes of conditioning. Similarly, gain increased in the plane of conditioning after adaptation to visual magnification (2X). The adaptive changes were greater at low (0.025–1 Hz) than at high (2.5–4 Hz) frequencies, and were more robust when gain was driven downward than upward. However, control (sham) adaptation experiments showed that VOR gain tended to drop slightly over 6 h in the absence of adaptive drive to do so, suggesting that the gain modifications may be more symmetric when referenced to the control. Adaptive VOR gain enhancement or decrement in the plane of conditioning did not result in systematic and parallel changes in orthogonal VOR planes.     

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     

Effects of lesion of the interstitial nucleus of Cajal on vestibular nuclear neurons activated by vertical vestibular stimulation

Summary 1. Experiments were performed in cats anesthetized with nitrous oxide to study the effects of INC lesions on responses of vestibular nuclear neurons during sinusoidal rotations of the head in the vertical (pitch) plane. Responses of neurons in the INC region were recorded during pitch rotations at 0.15 Hz. A great majority of these neurons did not respond to static pitch tilts, and they seemed to respond either to anterior or to posterior semicircular canal inputs with a peak phase lag of 140 deg (re head acceleration). 2. Responses of vestibular nuclei neurons in intact cats were recorded during pitch rotations at the same frequency (0.15 Hz). Neurons that seemed to respond to vertical semicircular canal inputs showed peak phase lags of 90 deg relative to head acceleration, whereas neurons that responded to static pitch tilts showed peak phase shifts near 0 deg. These results indicate that responses of neurons in the INC region lag those of vestibular neurons by about 50 deg, suggesting that the former neurons possess a phase-lagging (i.e. integrated) vestibular signal. 3. Responses of vestibular neurons in cats that had received electrolytic lesions of bilateral INCs 1–2 weeks previously were recorded during pitch rotations at the same frequency (0.15 Hz). Neurons that presumably responded to vertical semicircular canal inputs showed a peak phase lag of 60 deg relative to head acceleration, a significant decrease of the phase lag compared to normal, whereas responses near 0 deg were unchanged. Gain values of individual cells also significantly dropped from 2.07 ± 0.67 spikes · s⁻¹/deg · s⁻²2 (mean ± SD; normal cats) to 1.27 ± 0.68 spikes · s⁻²/deg · s⁻² (INC lesioned cats) at 0.15 Hz. When responses of vestibular neurons were studied during pitch rotations in the range of 0.044–0.49 Hz in these cats, a large decrease of the phase lag was observed at lower frequencies, whereas the slopes of phase lag curves of vestibular neurons in intact cats were rather flat. 4. Procaine infusion into the bilateral INCs not only resulted in a decrease of 20–50 deg in the phase lag in responses of vestibular neurons that had lagged head acceleration by 90–140 deg before procaine infusion, but also dropped the gain of the response to rotation by an average of 31%, whereas responses of neurons that had showed phase shifts near 0 deg were not influenced consistently. Simultaneous recording of the vestibular neurons and the vertical vestibuloocular reflex (VOR) indicated that the phase advance and gain drop of vestibular neurons occurred earlier than those of the VOR. These results exclude the possibility that the change in dynamic response of vestibular neurons after procaine infusion is due to depression of general brain stem activity that may lead to the phase advance of the VOR, and suggest that the decrease of the phase lag and gain drop in responses of the vestibular neurons was caused by removal of the phase-lagging, feedback signal coming from the INC to the vestibular nuclei.     

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 ×4 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 ×4 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. Received: 27 February 1998 / Accepted: 11 November 1998     

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     

Dynamics of the horizontal vestibuloocular reflex after unilateral labyrinthectomy: response to high frequency, high acceleration, and high velocity rotations

Loss of vestibular information from one labyrinth results in a marked asymmetry in the horizontal vestibuloocular reflex (VOR). The results of prior studies suggest that long-term deficits in VOR are more severe in response to rapid impulses than to sinusoidal head movements. The goal of the present study was to investigate the VOR following unilateral labyrinthectomy in response to different stimuli covering the full range of physiologically relevant head movements in macaque monkeys. The VOR was studied 1–39 days post-lesion using transient head perturbations (up to 12,000°/s²), rapid rotations (up to 500°/s), and sinusoidal rotations (up to 15 Hz). In response to rotations with high acceleration or velocity, both contra- and ipsilesional gains remained subnormal. VOR gains decreased as a function of increasing stimulus acceleration or velocity, reaching minimal values of 0.7–0.8 and 0.3–0.4 for contra and ipsilesional rotations, respectively. For sinusoidal rotations with low frequencies and velocities, responses to contralesional stimulation recovered within ∼ 4 days. With increasing velocities and frequencies of rotation, however, the gains of contra- and ipsilesional responses remained subnormal. For each of the most challenging stimuli tested (i.e., 12,000°/s² transient head perturbations, 500°/s fast whole-body rotations and 15 Hz stimulation) no significant compensation was observed in contra- or ipsilesional responses over time. Moreover, we found that gain of the cervico-ocular reflex (COR) remained negligible following unilateral loss indicating that neck reflexes did not contribute to the observed compensation. VOR responses elicited by both sinusoidal and transient rotations following unilateral labyrinthectomy could be described by the same mathematical model. We conclude that the compensated VOR has comparable response dynamics for impulses and sinusoidal head movements.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .     

Unilateral testing of utricular function

A modified rotatory chair test is reported in which radial acceleration, generated by eccentric displacement of the subject during constant angular velocity, is exploited as a unilateral stimulation to the otolith organs. During constant angular rate rotation, the test subject is displaced laterally on the rotating turntable by 3.5 cm, so that one labyrinth becomes aligned with the rotatory axis while the second – eccentric – labyrinth is solely exposed to the altered gravito-inertial acceleration (GIA). Previously reported results showed that the direction of the response is independent of the direction of turntable rotation, ruling out any canal influence, and indicated that in a normal population the response, measured in one eye, was symmetrical for displacement of the left and right labyrinths. This mode of stimulus thus appears to elicit a unilateral otolith-ocular response (OOR). Examination of this unilateral OOR was extended in the present study; comparative testing with head-tilt to gravity, i.e. involving bilateral stimulation to the otolith organs, was carried out. Movements of both eyes were recorded (by three-dimensional video-oculography), in order to examine response conjugacy. To verify the specificity of the unilateral stimulus, tests were performed with patients who had previously undergone unilateral section of the vestibular nerve as treatment for acoustic neuroma. The eccentric displacement profile (EDP) and head-tilt stimulus each included ten cycles of left-right oscillation in order to permit signal averaging. In the normal subjects (n=12) the torsional component of the OOR proved to be both labyrinth-symmetrical and conjugate, during both bilateral and unilateral otolith stimulation. OOR gain (ocular torsion/GIA tilt) was higher for bilateral than unilateral stimulation. Bilateral OORs, obtained from three of the five unilaterally deafferented patients, proved less symmetrical and conjugate than in the normals. Unilateral OORs in all five patients were characteristically asymmetrical, with little or no response during stimulation of the diseased labyrinth. Received: 28 July 1997 / Accepted: 3 February 1998     

Deficits of gaze stability in multiple axes following unilateral vestibular lesions

 Abnormalities in the vestibulo-ocular reflex (VOR) after unilateral vestibular injury may cause symptomatic gaze instability. We compared five subjects who had unilateral vestibular lesions with normal control subjects. Gaze stability and VOR gain were measured in three axes using scleral magnetic search coils, in light and darkness, testing different planes of rotation (yaw and pitch), types of stimulus (sinusoids from 0.8 to 2.4 Hz, and transient accelerations) and methods of rotation (active and passive). Eye velocity during horizontal tests reached saturation during high-velocity/acceleration ipsilesional rotation. Rapid vertical head movements triggered anomalous torsional rotation of the eyes. Gaze instability was present even during active rotation in the light, resulting in oscillopsia. These abnormal VOR responses are a consequence of saturating nonlinearities, which limit the usefulness of frequency-domain analysis of rotational test data in describing these lesions. Received: 22 April 1996 / Accepted: 18 February 1997     

Modeling spatial tuning of adaptation of the angular vestibulo-ocular reflex

Gain adaptation of the yaw angular vestibular ocular reflex (aVOR) induced in side-down positions has gravity-independent (global) and -dependent (localized) components. When the head oscillation angles are small during adaptation, localized gain changes are maximal in the approximate position of adaptation. Concurrently, polarization vectors of canal–otolith vestibular neurons adapt their orientations during these small-angle adaptation paradigms. Whether there is orientation adaptation with large amplitude head oscillations, when the head is not localized to a specific position, is unknown. Yaw aVOR gains were decreased by oscillating monkeys about a yaw axis in a side-down position in a subject–stationary visual surround for 2 h. Amplitudes of head oscillation ranged from 15° to 180°. The yaw aVOR gain was tested in darkness at 0.5 Hz, with small angles of oscillation (±15°) while upright and in tilted positions. The peak value of the gain change was highly tuned for small angular oscillations during adaptation and significantly broadened with larger oscillation angles during adaptation. When the orientation of the polarization vectors associated with the gravity-dependent component of the neural network model was adapted toward the direction of gravity, it predicted the localized learning for small angles and the broadening when the orientation adaptation was diminished. The model-based analysis suggests that the otolith orientation adaptation plays an important role in the localized behavior of aVOR as a function of gravity and in regulating the relationship between global and localized adaptation.     

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.     

Off-center yaw rotation: effect of naso-occipital linear acceleration on the nystagmus response of normal human subjects and patients after unilateral vestibular loss

 Dual search coils were used to record horizontal, vertical and torsional eye movement components of one eye during nystagmus caused by off-center yaw rotation (yaw centrifugation). Both normal healthy human subjects (n=7) and patients with only one functioning labyrinth (n=12) were studied in order to clarify how the concomitant linear acceleration affected the nystagmus response. Each subject was seated with head erect on the arm of a fixed-chair human centrifuge, 1 m away from the center of the rotation, and positioned to be facing along a radius; either towards (facing-in) or away from (facing-out) the center of rotation. Both yaw right and yaw left angular accelerations of 10°s^–2 from 0 to 200°/s were studied. During rotation a centripetal linear acceleration (increasing from 0 to 1.24×g units) was directed along the subject’s naso-occipital axis resulting in a shift of the resultant angle of the gravitoinertial acceleration (GIA) of 51° in the subject’s pitch plane and an increase in the total GIA magnitude from 1.0 to 1.59×g. In normal subjects during the angular acceleration off-center there were, in addition to the horizontal eye velocity components, torsional and vertical eye velocities present. The magnitude of these additional components, although small, was larger than observed during similar experiments with on-center angular acceleration (Haslwanter et al. 1996), and the change in these components is attributed to the additional effect of the linear acceleration stimulation. In the pitch plane the average size of the shift of the axis of eye velocity (AEV) during the acceleration was about 8° for a 51° shift of the GIA (around 16% of the GIA shift) so that the AEV-GIA alignment was inadequate. There was a very marked difference in the size of the AEV shift depending on whether the person was facing-in [AEV shift forward (i.e. non-compensatory) of about 4°] or facing-out [AEV shift forward (i.e. compensatory) of around 12°]. The linear acceleration decreased the time constant of decay of the horizontal component of the post-rotatory nystagmus: from an average of 24.8°/s facing-in to an average of 11.3°/s facing-out. The linear acceleration dumps torsional eye velocity in an manner analogous to, but independent of, the dumping of horizontal eye velocity. Patients with UVD had dramatically reduced torsional eye velocities for both facing-in and facing-out headings, and there was little if any shift of the AEV in UVD patients. The relatively small effects of linear acceleration on human canal-induced nystagmus found here confirms other recent studies in humans (Fetter et al. 1996) in contrast to evidence from monkeys and emphasizes the large and important differences between humans and monkeys in otolith-canal interaction. Our results confirm the vestibular control of the axis of eye velocity of humans is essentially head-referenced whereas in monkeys that control is essentially space-referenced. Received: 22 September 1997 / Accepted: 30 June 1998     

Effects of unilateral vestibular deafferentation on the linear vestibulo-ocular reflex evoked by impulsive eccentric roll rotation

The effects of unilateral vestibular deafferentation (UVD) on the linear vestibulo-ocular reflex (LVOR) were studied by measuring three-dimensional eye movements in seven UVD subjects evoked by impulsive eccentric roll rotation while viewing an earth-fixed target at 200, 300, or 600 mm and comparing their responses to 11 normal subjects. The stimulus, a whole-body roll of approximately 1 degrees, with the eye positioned 815 mm eccentric to the rotation axis, produced an inter-aural linear acceleration of approximately 0.5 g and a roll acceleration of approximately 360 degrees /s(2). The responses generated by the LVOR comprise horizontal eye rotations. Horizontal eye velocity at 100 ms from stimulus onset in UVD subjects was significantly lower than in normal subjects for all viewing distances, with no significant difference between ipsilesional and contralesional responses. LVOR acceleration gain, defined as the slope of actual horizontal eye velocity divided by the slope of ideal horizontal eye velocity during a 30-ms period starting 70 ms from stimulus onset, was bilaterally significantly reduced in UVD subjects at all viewing distances. Acceleration gain from all viewing distances was 1.04 +/- 0.28 in normal subjects, and in UVD subjects was 0.49 +/- 0.23 for ipsilesional and 0.63 +/- 0.27 for contralesional acceleration. LVOR enhancement in the first 100 ms by near viewing was still present in UVD subjects. LVOR latency in UVD subjects (approximately 39 ms) was not significantly different from normal subjects (approximately 36 ms). After UVD, LVOR is bilaterally and largely symmetrically reduced, but latency remains unchanged and modulation by viewing distance is still present.     

High acceleration impulsive rotations reveal severe long-term deficits of the horizontal vestibulo-ocular reflex in the guinea pig

 While there is agreement that unilateral vestibular deafferentation (UVD) invariably produces an immediate severe horizontal vestibulo-ocular reflex (HVOR) deficit, there is disagreement about whether or not this deficit recovers and, if so, whether it recovers fully or only partly. We suspected that this disagreement might mainly be due to experimental factors, such as the species studied, the means chosen to carry out the UVD, or the nature of the test stimulus used. Our aim was to sort out some of these factors. To do this, we studied the HVOR of alert guinea pigs in response to low and high acceleration sinusoidal and high acceleration impulses after UVD by either labyrinthectomy or by vestibular neurectomy. The HVOR in response to high acceleration impulsive yaw rotations was measured before, and at various times after, either unilateral labyrinthectomy or superior vestibular neurectomy. Following UVD, there was a severe impairment of the HVOR for ipsilesional rotations and a slight impairment for contralesional rotations, after either operation. This asymmetrical HVOR deficit in the guinea pig parallels the deficit observed in humans. Between the first measurement, which was made 1 week after UVD, and the last, which was made 3 months after UVD, there was no change in the HVOR. This lack of recovery was the same after labyrinthectomy as after vestibular neurectomy. The HVOR to low and high acceleration sinusoidal yaw rotations were measured after UVD, and the results were compared with those in response to impulsive rotations. For low acceleration sinusoidal rotations (250°/s²), the gain was symmetrical, although reduced bilaterally. As the peak head acceleration increased, the HVOR became increasingly asymmetric. The HVOR asymmetry for sinusoidal rotations was significantly less than for impulsive rotations that had the same high peak head acceleration (2500°/s²). Our results show that the HVOR deficit after UVD is the same in guinea pigs as in humans; that it is the same after vestibular neurectomy as after labyrinthectomy; that it is lasting and severe in response to high acceleration rotations; and, that it is more obvious in response to impulses than to sinusoids. Received: 11 March 1998 / Accepted: 2 June 1998