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Inverse U-shaped curve for age dependency of torsional eye movement responses to galvanic vestibular stimulation.

To investigate age dependent changes we analysed torsional eye movement responses to binaural and monaural galvanic vestibular stimulation (GVS) in 57 healthy subjects (20-69 years old). GVS (1-3 mA) induced torsional eye movements consisting of static torsion toward the anode (amplitude 1-6 degrees ) and superimposed torsional nystagmus (slow phase velocity 0.5-3 degrees /s, quick phase amplitude 0.5-2 degrees, nystagmus frequency 0.75-1.5 s-1). Static ocular torsion and torsional nystagmus increased from the third to the sixth decade and decreased in older subjects, e.g. slow phase velocity increased from 1.5 degrees /s (20-29 years) to 2.9 degrees /s (50-59 years) and decreased to 2.5 degrees /s for the seventh decade (60-69 years). Thus, an inverse U-shaped curve was found for the dependence of torsional eye movement responses on age. All structures relevant for vestibular function degenerate with age, but at varying times. Since hair cell loss precedes those seen in the vestibular nerve and Scarpa's ganglion, the decrease in hair cell counts could be compensated for by increased sensitivity of afferent nerve fibres or central mechanisms. Increased sensitivity could thus maintain normal function despite reduced peripheral input. As GVS acts at the vestibular nerve (thereby bypassing the hair cells), electrical stimulation should be more efficient in subjects with the beginning of hair cell degeneration, as seen in our data up to the sixth decade. The degeneration of nerve fibres, ganglion cells and central neurons becomes evident at older ages. Thus, the compensatory increase in sensitivity breaks down and GVS-induced eye movements decline-a finding that is reflected by the inverse U-shaped curve for age dependency presented in this study.

Adult↗

Influence of gaze rotation on the visual response of primate MSTd neurons.

When we move forward, the visual image on our retina expands. Humans rely on the focus, or center, of this expansion to estimate their direction of heading and, as long as the eyes are still, the retinal focus corresponds to the heading. However, smooth rotation of the eyes adds nearly uniform visual motion to the expanding retinal image and causes a displacement of the retinal focus. In spite of this, humans accurately judge their heading during pursuit eye movements and during active, smooth head rotations even though the retinal focus no longer corresponds to the heading. Recent studies in macaque suggest that correction for pursuit may occur in the dorsal aspect of the medial superior temporal area (MSTd) because these neurons are tuned to the retinal position of the focus and they modify their tuning during pursuit to compensate partially for the focus shift. However, the question remains whether these neurons also shift focus tuning to compensate for smooth head rotations that commonly occur during gaze tracking. To investigate this question, we recorded from 80 MSTd neurons while monkeys tracked a visual target either by pursuing with their eyes or by vestibulo-ocular reflex cancellation (VORC; whole-body rotation with eyes fixed in head and head fixed on body). VORC is a passive, smooth head rotation condition that selectively activates the vestibular canals. We found that neurons shift their focus tuning in a similar way whether focus displacement is caused by pursuit or by VORC. Across the population, compensation averaged 88 and 77% during pursuit and VORC, respectively (tuning shift divided by the retinal focus to true heading difference). Moreover the degree of compensation during pursuit and VORC was correlated in individual cells (P < 0.001). Finally neurons that did not compensate appreciably tended to be gain-modulated during pursuit and VORC and may constitute an intermediate stage in the compensation process. These results indicate that many MSTd cells compensate for general gaze rotation, whether produced by eye-in-head or head-in-world rotation, and further implicate MSTd as a critical stage in the computation of heading. Interestingly vestibular cues present during VORC allow many cells to compensate even though humans do not accurately judge their heading in this condition. This suggests that MSTd may use vestibular information to create a compensated heading representation within at least a subpopulation of cells, which is accessed perceptually only when additional cues related to active head rotations are also present.

Action Potentials↗

Resolution of sensory ambiguities for gaze stabilization requires a second neural integrator.

The ability to simultaneously move in the world and maintain stable visual perception depends critically on the contribution of vestibulo-ocular reflexes (VORs) to gaze stabilization. It is traditionally believed that semicircular canal signals drive compensatory responses to rotational head disturbances (rotational VOR), whereas otolith signals compensate for translational movements [translational VOR (TVOR)]. However, a sensory ambiguity exists because otolith afferents are activated similarly during head translations and reorientations relative to gravity (i.e., tilts). Extra-otolith cues are, therefore, necessary to ensure that dynamic head tilts do not elicit a TVOR. To investigate how extra-otolith signals contribute, we characterized the temporal and viewing distance-dependent properties of a TVOR elicited in the absence of a lateral acceleration stimulus to the otoliths during combined translational/rotational motion. We show that, in addition to otolith signals, angular head position signals derived by integrating sensory canal information drive the TVOR. A physiological basis for these results is proposed in a model with two distinct integration steps. Upstream of the well known oculomotor velocity-to-position neural integrator, the model incorporates a separate integration element that could represent the "velocity storage integrator," whose functional role in the oculomotor system has so far remained controversial. We propose that a key functional purpose of the velocity storage network is to temporally integrate semicircular canal signals, so that they may be used to extract translation information from ambiguous otolith afferent signals in the natural and functionally relevant bandwidth of head movements.

Animals↗

Temporal firing patterns of Purkinje cells in the cerebellar ventral paraflocculus during ocular following responses in monkeys I. Simple spikes.

The simple-spike firing frequency of 30 Purkinje cells (P cells) in the ventral paraflocculus (VPFL) of alert monkeys was studied in relation to vertical slow eye movements, termed ocular following response (OFR), induced by large-field visual motions of different velocities and durations. To quantitatively analyze the relationship between eye movement and firing frequency, an inverse dynamics representation of the eye movement was used for reconstructing the temporal waveform of firing. Coefficients of eye-acceleration, velocity, and position, bias, and time lag between firing and eye movement were estimated by least-square error method. In the regression analyses for each stimulus condition, 86% (146/170) of the well-modulated temporal firing patterns taken from those 30 P cells were reconstructed successfully from eye movement. The model with acceleration, velocity, and position terms, which we used, was shown as the best among several potential models by Cp statistics, consistent with t-test of significance of each term. Reliable coefficients were obtained from 75% (109/146) of the well-reconstructed firing patterns of 28 cells among 30. The estimated coefficients were larger (statistically significant) for slow stimuli than for fast stimuli, suggesting changes in sensitivities under different conditions. However, firing patterns of each cell under several different conditions were frequently well reconstructed by an inverse dynamics representation with a single set of coefficients (13 cells among 21). This indicates that the relationships between P cell firing and OFR are roughly linear in those stimulus ranges. The estimated coefficients for acceleration and velocity suggested that the VPFL P cells properly encode the dynamic components of the motor command during vertical OFR. As for the positional component, however, these P cells are correlated with eye movement in the opposite direction. In the regression analysis without positional component, remarkable differences between observed and reconstructed firing patterns were noted especially in the initial phase of the movements, indicating that the negative positional component was not negligible during OFR. Thus we conclude that, during OFR, the VPFL P cells cannot provide the necessary final motor command, and other brain regions, downstream neural structures, or other types of P cells must provide lacking position-dependent motor commands. This finding about the negative correlation with the position is in the opposite sign with previous studies obtained from the fixation and the smooth pursuit movement. From these comparisons, how the VPFL contributes to a part of the final motor command or how other brain regions complement the VPFL is suggested to be different for early and late phases of the movements.

Action Potentials↗

Short-term vestibulo-ocular reflex adaptation in humans. II. Error signals.

We oscillated humans sinusoidally at 0.2 Hz for 1 h, using various combinations of rotations of the head and visual surround to elicit short-term adaptation of the gain of the vestibulo-ocular reflex (VOR). Before and after each period of training, the gain of the VOR was measured in darkness, in response to a position step of head rotation. A small foveal target served as well as a full-field stimulus at driving VOR adaptation. Oscillation of the visual surround alone produced a substantial increase in the VOR gain. When the visual scene was rotated in phase with the head but with a larger amplitude to produce a reversal of the VOR, the VOR gain increased if the movement of the visual scene was much greater than that of the head, otherwise the gain decreased. We interpreted these results with a model of VOR adaptation that uses as its "error signal" the combination of motion of images on the retina (retinal slip) and any additional slow-phase eye velocity, beyond that generated by the VOR through the vestibular nuclei, necessary to prevent such retinal slip during head rotation. The slow phase velocity generated by the VOR is derived from "inferred head rotation", a signal based on the discharge of neurons in the vestibular nuclei that receive both labyrinthine and visual (optokinetic) inputs. The amplitude and sign of the ratio of the "error signal" to "inferred head velocity" determined the amplitude and the direction (increase or decrease) of VOR gain adaptation.

Adaptation, Physiological↗

Full-body gaze control mechanisms elicited during locomotion: effects of VOR adaptation.

We have previously shown that multiple, interdependent, full- body sensorimotor subsystems aid gaze stabilization during locomotion. In the present study we investigated how the full-body gaze control system responds following exposure to visual-vestibular conflict known to adaptively modify vestibulo-ocular reflex (VOR) function. Subjects (n = 14) walked (6.4 km/h) on a motorized treadmill before and after they were exposed to 0.5X minifying lenses worn for 30 minutes during self-generated sinusoidal vertical head rotations performed while seated. Results indicate that, following the exposure the major changes that subjects showed were to: 1) decrease the amplitude of head pitch and vertical translation of the torso movement with respect to space; 2) increase the amount of knee and ankle flexion during the initial stance phase of the gait cycle. A correlation analysis showed that: 1) changes in the head pitch significantly co-varied with that of the vertical torso translation 2) changes in the knee flexion significantly co-varied with that of the ankle flexion during the initial stance phase of the gait cycle 3) changes in the vertical torso translation significantly co-varied with that of the ankle flexion during the initial stance phase of the gait cycle. Thus we infer that the changes in the magnitude after VOR adaptation in comparison to their pre adaptation responses serve to aid gaze stabilization during locomotion. The significant covariation of the changes between subsystems provides further evidence that the full body contributes to gaze stabilization during locomotion, and its different functional elements are subject to adaptive reorganization following exposure to visual-vestibular conflict.

Adaptation, Physiological↗

Eye-head coordination during postural perturbation as a predictor of falls in community-dwelling elderly women.

OBJECTIVES: To assess the functional significance of eye-head coordination during postural perturbations and to determine the contribution of angular vestibulo-ocular reflex (AVOR) suppression to the prediction of 1-year fall history in community-dwelling elderly women. DESIGN: Descriptive analysis of factors correlated with falls. SETTING: Community-based independent and senior assisted living facilities. PARTICIPANTS: Volunteer sample of 38 older women (mean age +/- standard deviation, 81.6+/-3.9y; range, 74-92y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Multiple and logistic regression variables (slope coefficients, partial R2, percent-correct fall history classifications) and fall prediction equations generated by using minimal sets of predictor variables. RESULTS: Instantaneous AVOR gain and sedative use were predictors of 1-year history of falls in all minimal sets of predictor variables. R2 for the prediction models varied from.47 to.62 and indicated substantial shared variance with the 1-year history of falling. Elderly women who failed to suppress the AVOR gain were 18 times more likely to have experienced a fall in the past year compared with elderly women who showed AVOR suppression (odds ratio=18; 95% confidence interval, 1.63-198.42). CONCLUSIONS: When controlling for all other variables in the model, instantaneous AVOR gain accounted for nearly 30% of the variance of fall history. The strong association between 1-year fall history, the use of sedatives, and changes in the AVOR gain supports a functional link between AVOR suppression and effective balance in elderly women.

Accidental Falls↗

Targeting errors and reduced oculomotor range following ablations of the superior colliculus or pretectum/thalamus.

The physiology of the superior colliculus (SC) implicates it in the visual control of eye movements. In the primate, acute inactivation of the superior colliculus delays the onset of a visually guided saccade, slows its velocity, and shortens its amplitude. Previous research leaves uncertain whether other oculomotor disorders which sometimes follow ablation of this structure are due to tectal pathology, to neural damage surrounding the tectum, or to both causes. In this study, 7 cynomolgus monkeys received SC ablations. In 3 others, control lesions were placed in the pretectal/posterior thalamic region. Both procedures produced a qualitatively similar syndrome of 4 oculomotor changes. Reaction time to initiate saccades to visual targets was slowed. Secondly, the surgery constricted the normal ocular range. At the worst, movement was confined to a radius of 10-12 degrees of primary gaze. The monkeys displayed two kinds of inaccuracies when attempting to foveate stationary visual targets within their surviving ocular range. Saccadic amplitude was reduced, causing the monkeys' initial attempt to fall short of foveating the target. If the target remained lighted there then ensued a series of stepwise corrective saccades toward it. The corrective saccades ceased with the eyes still at a position short of the target. Eye position remained in error for the duration of the trial. The final position was independent of the target's retinal position or the vector of the motor command needed to acquire the target. Rather, the error was related to the angular position of the target about the head ( = desired eye position). The syndrome appeared qualitatively similar whether resulting from tectal or the more rostral pretectal/diencephalic ablation. When occurring along the horizontal axis, the deficits appeared to require damage to the superior colliculus, perhaps combined with pathology of some other structure. The same syndrome along the vertical axis was better correlated with pretectal/diencephalic pathology. Invasion of these areas together with invasion of the transthalamic axons from the frontal eye fields is interpreted as the critical pathology responsible for the syndrome. A similar oculomotor trajectory can be modelled by supposing a loss in the gain of the signal which conveys the target's retinal position, combined with one other fault in the circuit: either a loss in gain of the eye position signal, or the signal representing the target's position in craniocentric coordinates.

Animals↗

[Skew deviation].

BACKGROUND: Skew deviation is a vertical ocular misalignment of prenuclear origin. Although well described in the literature, it is still probably underdiagnosed. Natural history of skew deviation is not well described in the literature. PURPOSE: To describe the clinical presentations, etiologies and follow-up of skew deviation. METHODS: Retrospective study of 29 patients diagnosed with skew deviation between 1993 and 1996. RESULTS: The commonest cause was cerebrovascular accident (12/29) and the commonest localisation was mesencephalic (9/29). Other causes included surgery (7/29), tumor (4/29), trauma (3/29), degeneration (3/29), inflammatory (2/29), increased intracranial pressure (1/29). Other localisations included cerebellum (5/29), ponto-mesencephalic (3/29), and medulla (2/29). Vertical diplopia was always accompanied by other neuro-ophthalmologic abnormalities. 69.2% (18/26) patients were totally asymptomatic after 7.5 months. 30.8% (8/26) were still symptomatic (diplopia). One patient required surgery, three patients were relieved with prisms, one patient needed monocular occlusion. One patient died during follow-up and precise data were lacking in two symptomatic patients. CONCLUSION: Skew deviation is not so rare, 10% of the cases referred to us for diplopia in 3 years. The diagnosis of skew deviation should be entertained when vertical diplopia cannot be explained by pathology of extraocular muscles, peripheral or central cranial nerve III or IV palsies, myasthenia, or orbital pathology. Prognosis for recovery in patients with skew deviation is good. 70% will recover, after a median time of 7.5 months. Surgery should be postponed at least for 12 months.

Adolescent↗

Adaptive plasticity in the naso-occipital linear vestibulo-ocular reflex.

The linear vestibulo-ocular reflex (LVOR) during motion along the naso-occipital (NO) axis is governed by eye position and viewing distance. These influences are necessary for the LVOR to maintain stable foveal images during head translation. The response to NO translation must be large when eye position is eccentric from the axis of head motion (i.e., during lateral gaze) and must diminish as eye position approaches straight-ahead, eventually reaching zero when the eye is aligned with the NO axis of motion (the "null point"). As eye position crosses to the opposite side, the LVOR response must reappear, but in the opposite direction, and must grow in magnitude as eccentricity increases. To determine whether the NO-LVOR is subject to adaptive plastic mechanisms, squirrel monkeys were conditioned during NO translation while they binocularly viewed a rich visual field through parallel base-right or base-left wedge prisms. This optical method effectively shifted the visual world 9 degrees leftward or rightward, respectively, thus inducing a mismatch between vision and the NO-LVOR during head movements. To restore compensatory function, the relationship between LVOR sensitivity and horizontal eye position must shift by 9 degrees in the same direction as the visual image shift, effectively shifting the null point. After 2 h of adaptive conditioning, all monkeys exhibited an adaptive shift in the appropriate direction by an average of 3.0 degrees (range 0.7-5.0 degrees), corresponding to 33% of the geometrically required adaptation.

Adaptation, Physiological↗

Firing behaviour of squirrel monkey eye movement-related vestibular nucleus neurons during gaze saccades.

The firing behaviour of vestibular nucleus neurons putatively involved in producing the vestibulo-ocular reflex (VOR) was studied during active and passive head movements in squirrel monkeys. Single unit recordings were obtained from 14 position-vestibular (PV) neurons, 30 position-vestibular-pause (PVP) neurons and 9 eye-head-vestibular (EHV) neurons. Neurons were sub-classified as type I or II based on whether they were excited or inhibited during ipsilateral head rotation. Different classes of cell exhibited distinctive responses during active head movements produced during and after gaze saccades. Type I PV cells were nearly as sensitive to active head movements as they were to passive head movements during saccades. Type II PV neurons were insensitive to active head movements both during and after gaze saccades. PVP and EHV neurons were insensitive to active head movements during saccadic gaze shifts, and exhibited asymmetric sensitivity to active head movements following the gaze shift. PVP neurons were less sensitive to on-direction head movements during the VOR after gaze saccades, while EHV neurons exhibited an enhanced sensitivity to head movements in their on direction. Vestibular signals related to the passive head movement were faithfully encoded by vestibular nucleus neurons. We conclude that central VOR pathway neurons are differentially sensitive to active and passive head movements both during and after gaze saccades due primarily to an input related to head movement motor commands. The convergence of motor and sensory reafferent inputs on VOR pathways provides a mechanism for separate control of eye and head movements during and after saccadic gaze shifts.

Animals↗

Neural control of rotational kinematics within realistic vestibuloocular coordinate systems.

Previous theoretical investigations of the three-dimensional (3-D) angular vestibuloocular reflex (VOR) have separately modeled realistic coordinate transformations in the direct velocity path or the nontrivial problems of converting angular velocity into a 3-D orientation command. We investigated the physiological and behavioral implications of combining both approaches. An ideal VOR was simulated using both a plant model with head-fixed eye muscle actions (standard plant) and one with muscular position dependencies that facilitate Listing's law (linear plant). In contrast to saccade generation, stabilization of the eye in space required a 3-D multiplicative (tensor) interaction between the various components of velocity and position in both models: in the indirect path of the standard plant version, but also in the direct path of the linear plant version. We then incorporated realistic nonorthogonal coordinate transformations (with the use of matrices) into both models. Each now malfunctioned, predicting ocular drift/retinal destabilization during and/or after the head movement, depending on the plant version. The problem was traced to the standard multiplication tensor, which was only defined for right-handed, orthonormal coordinates. We derived two solutions to this problem: 1) separating the brain stem coordinate transformation into two (sensory and motor) transformations that reordered and "undid" the nonorthogonalities of canals and muscle transformations, thus ensuring orthogonal brain stem coordinates, or 2) computing the correct tensor components for velocity-orientation multiplication in arbitrary coordinates. Both solutions provided an ideal VOR. A similar problem occurred with partial canal or muscle damage. Altering a single brain stem transformation was insufficient because the resulting coordinate changes rendered the multiplication tensor inappropriate. This was solved by either recomputing the multiplication tensor, or recomputing the appropriate internal sensory or motor matrix to normalize and reorthogonalize the brain stem. In either case, the multiplication tensor had to be correctly matched to its coordinate system. This illustrates that neural coordinate transformations affect not only serial/parallel projections in the brain, but also lateral projections associated with computations within networks/nuclei. Consequently, a simple progression from sensory to motor coordinates may not be optimal. We hypothesize that the VOR uses a dual coordinate transformation (i.e., both sensory and motor) to optimize intermediate brain stem coordinates, and then sets the appropriate internal tensor for these coordinates. We further hypothesize that each of these processes should optimally be capable of specific, experimentally identifiable adjustments for motor learning and recovery from damage.

Brain Stem↗

Predicting the duration of ocular pursuit in humans.

This study examines the effects of expectation on the timing of ocular pursuit termination. Human subjects pursued repeated, constant velocity (15 or 30 degrees/s) target motion stimuli (ramps), moving left or right. Ramps were of constant duration (RD = 240, 480, 720 or 960 ms), resulting in anticipatory slowing of eye velocity prior to ramp termination and target extinction. At unexpected intervals RD was increased or decreased, but velocity remained constant. When RD increased eye velocity continued to decline, even though the target remained visible and continued to move. It took approximately 180 ms before eye velocity started to recover towards the steady state velocity level for the continued target motion. When RD decreased, eye velocity continued as if for a longer ramp duration, again taking approximately 180 ms before eye velocity started to decrease. These results suggest that timing of the response to the expected ramp duration had been pre-programmed on the basis of prior experience of ramp duration. Moreover, adjustments to timing occurred rapidly, within the second presentation of the new RD. Responses were compared to control conditions with randomised ramp duration. Eye velocity declined later in the controls for RD < or = 720 ms, as expected, but exhibited similar decline in predictable and randomised conditions for RD = 960 ms. Further controls established that eye velocity could only be reliably maintained until the end of the ramp when the target was expected to continue in motion after the end of the ramp. The results suggest that estimates of stimulus duration are made continuously in all conditions, based on expectancy of target termination.

Adult↗

Human angular vestibulo-ocular reflex initiation: relationship to Listing's law.

An ideal vestibulo-ocular reflex (VOR) generates ocular rotations compensatory for head motion. During visually guided movements, Listing's law (LL) constrains eye rotation to axes in Listing's plane (LP). Recently, it has been reported that the VOR axis is not collinear with the rotation axis of the head, but is influenced by eye position in the orbit. Elaborate models have been proposed suggesting dynamic neural control of the VOR axis. By examining the variability and time course of changes in VOR axis orientation, we sought to test plausibility of these models. Binocular LPs were defined in eight humans. The VOR was evoked by a highly repeatable, transient, whole-body yaw rotation in darkness at peak acceleration 2800 deg/s2. Immediately prior to rotation, subjects regarded targets at eye level, 20 degrees up, or 20 degrees down. Eye and head positions were expressed in LP coordinates for comparison with LL. Eye position generally followed head position and departed LP when the head axis tilted out of LP. In the velocity domain the VOR axis tilted 28 +/- 9% of the change in vertical eye position, but there was significant intrasubject variation (14% to 41%). This roughly "quarter-angle" behavior began with the earliest detectable VOR. Given the brief latency and marked interindividual variability of the eye position dependence of the VOR rotational axis, and the small deviation of the VOR from LL in the position domain, it is speculated that this behavior is largely due to orbital mechanics interacting with the basic neural commands that initiate the VOR.

Adult↗

[Skin electrodes for electroretinography in unsedated children].

Contact lens electrode ERG is not well tolerated by children. So far, skin electrode ERG has suffered from a weakly defined geometrical relationship to the sources of ERG potentials. Because of the cuplike electric ocular field distribution, skin electrodes were placed: (1) in the middle of the lower eyelid (in order to be positioned in close proximity to the anterior apex of the cornea, which belongs to the electropositive inner surface of the cup); (2) 20 mm laterally to the temporal canthus (in proximity to the cup's electronegative outer surface). (3) Grounding was achieved by attaching a third skin electrode in the forehead midline. Instead of complete dark adaptation, adaptive illumination of 0.1 cd.m-2 was used to avoid frightening the children. After 10 min of adaptation, the examination started. Feeling safe on mother's lap, the little patient looked into a frosted glass screen (about 75 degrees of visual angle, depicting Mickey Mouse) on which a series of strobe flashes was delivered along the lines of the ISCEV ERG Standard: (1) blue flashes: filter no. 625 (Röhm and Haas); repetition rate 0.1 Hz; stimulus strength of white flashes 1.5 cd.m-2 s; (2) red flashes: filter no. S502 (Röhm and Haas); repetition rate 1 Hz; stimulus strength of white flashes 21.75 cd.m-2.s; (3) weak white flashes: stimulus strength 1.5 cd.m-2.s; repetition rate 0.3 Hz; (4) strong white flashes: stimulus strength 11.25 cd.m-2.s; repetition rate 0.3 Hz; (5) white flicker flashes: stimulus strength 1.5 cd.m-2.s; frequency 10, 30, 60 Hz. Recording of single stimulus responses turned out to be feasible; however, to achieve the best results, between 8 and 32 ERG responses were averaged. To illustrate the benefits of skin electrode ERGs in practice, the results of some cases are presented and discussed with respect to clinical findings.

Child↗

Gaze-stabilizing deficits and latent nystagmus in monkeys with early-onset visual deprivation: role of the pretectal not.

We studied the role of the pretectal nucleus of the optic tract (NOT) in the development of monocular optokinetic nystagmus (OKN) asymmetries and latent nystagmus (LN) in two monkeys reared with binocular deprivation (BD) caused by binocular eyelid suture for either the first 25 or 55 days of life. Single-unit recordings were performed in the right and left NOT of both monkeys at 2-3 yr of age and compared with similar unit recordings in normally reared monkeys. We also examined ocular motor behavior during electrical stimulation of the NOT and during pharmacological inactivation and activation using GABA(A) agonists and antagonists. In BD animals a large proportion of NOT units was dominated by the contralateral eye, in striking contrast to normal animals where 100% of NOT units were sensitive to stimuli delivered to either eye. In the 55-day BD animal no binocularly sensitive neurons were found, while in the 25-day BD animal 60% of NOT units retained at least some binocular sensitivity. Differences in direction sensitivity were also observed in BD animals. We found that 56% of units in the 55-day BD monkey and 10% of units in the 25-day BD monkey responded preferentially to contraversive visual motion. In contrast, only 5% of the NOT units encountered in normally reared monkeys respond preferentially during contraversive visual motion, the rest were most sensitive to ipsiversive visual motion. NOT neurons of BD monkeys showed a wide range of speed sensitivities similar to that of normal monkeys. Unilateral electrical stimulation of the NOT in BD animals induced a conjugate nystagmus with slow phases directed toward the side of stimulation. When we blocked the activity of NOT units with muscimol, a potent GABA(A) agonist, LN was abolished. In contrast, LN was increased when spontaneous activity of the NOT was enhanced with bicuculline, a GABA(A) antagonist. Our results indicate that the NOT in BD monkeys plays an important role in the OKN deficits and LN generation during monocular viewing. We hypothesize that the large proportion of units dominated by the contralateral eye contribute to the development of monocular OKN asymmetries and LN.

Animals↗

Phase-plane analysis of gaze stabilization to high acceleration head thrusts: a continuum across normal subjects and patients with loss of vestibular function.

We investigated the vestibulo-ocular reflex (VOR) during high-acceleration, yaw-axis, head rotations in 12 normals and 15 patients with vestibular loss [7 unilateral vestibular deficient (UVD) and 8 bilateral vestibular deficient (BVD)]. We analyzed gaze stabilization within a 200-ms window after head rotation began, using phase planes, which allowed simultaneous analysis of gaze velocity and gaze position. These "gaze planes" revealed critical dynamic information not easily gleaned from traditional gain measurements. We found linear relationships between peak gaze-velocity and peak gaze-position error when normalized to peak head speed and position, respectively. Values fell on a continuum, increasing from normals, to normals tested with very high acceleration (VHA = 10,000-20,000 degrees/s2), to UVD patients during rotations toward the intact side, to UVD patients during rotations toward the lesioned side, to BVD patients. We classified compensatory gaze corrections as gaze-position corrections (GPCs) or gaze-velocity error corrections (GVCs). We defined patients as better-compensated when the value of their end gaze position was low relative to peak gaze position. In the gaze plane this criterion corresponded to relatively stereotyped patterns over many rotations, and appearance of high velocity (100-400 degrees/s) GPCs in the gaze plane ending quadrant (150-200 ms after head movement onset). In less-compensated patients, and normals at VHA, more GVCs were generated, and GPCs were generated only after gaze-velocity error was minimized. These findings suggest that challenges to compensatory vestibular function can be from vestibular deficiency or novel stimuli not previously experienced. Similar patterns of challenge and compensation were observed in both patients with vestibular loss and normal subjects.

Acceleration↗

Human oculomotor system accounts for 3-D eye orientation in the visual-motor transformation for saccades.

A recent theoretical investigation has demonstrated that three-dimensional (3-D) eye position dependencies in the geometry of retinal stimulation must be accounted for neurally (i.e., in a visuomotor reference frame transformation) if saccades are to be both accurate and obey Listing's law from all initial eye positions. Our goal was to determine whether the human saccade generator correctly implements this eye-to-head reference frame transformation (RFT), or if it approximates this function with a visuomotor look-up table (LT). Six head-fixed subjects participated in three experiments in complete darkness. We recorded 60 degrees horizontal saccades between five parallel pairs of lights, over a vertical range of +/-40 degrees (experiment 1), and 30 degrees radial saccades from a central target, with the head upright or tilted 45 degrees clockwise/counterclockwise to induce torsional ocular counterroll, under both binocular and monocular viewing conditions (experiments 2 and 3). 3-D eye orientation and oculocentric target direction (i.e., retinal error) were computed from search coil signals in the right eye. Experiment 1: as predicted, retinal error was a nontrivial function of both target displacement in space and 3-D eye orientation (e.g., horizontally displaced targets could induce horizontal or oblique retinal errors, depending on eye position). These data were input to a 3-D visuomotor LT model, which implemented Listing's law, but predicted position-dependent errors in final gaze direction of up to 19.8 degrees. Actual saccades obeyed Listing's law but did not show the predicted pattern of inaccuracies in final gaze direction, i.e., the slope of actual error, as a function of predicted error, was only -0. 01 +/- 0.14 (compared with 0 for RFT model and 1.0 for LT model), suggesting near-perfect compensation for eye position. Experiments 2 and 3: actual directional errors from initial torsional eye positions were only a fraction of those predicted by the LT model (e. g., 32% for clockwise and 33% for counterclockwise counterroll during binocular viewing). Furthermore, any residual errors were immediately reduced when visual feedback was provided during saccades. Thus, other than sporadic miscalibrations for torsion, saccades were accurate from all 3-D eye positions. We conclude that 1) the hypothesis of a visuomotor look-up table for saccades fails to account even for saccades made directly toward visual targets, but rather, 2) the oculomotor system takes 3-D eye orientation into account in a visuomotor reference frame transformation. This transformation is probably implemented physiologically between retinotopically organized saccade centers (in cortex and superior colliculus) and the brain stem burst generator.

Adult↗