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David S Zee

Publications and source records attributed to David S Zee.

At least 19 recordsLinked to original sources
PubMed2006

What clinical disorders tell us about the neural control of saccadic eye movements.

Saccades are rapid eye movements that redirect the fovea from one object to another. A great deal has been learned about the anatomy and physiology of saccades, making them an ideal system for studying the neural control of movement. Basic research on normal eye movements has greatly increased our understanding of saccadic performance, anatomy and physiology, and led to a large number of control system models. These models simulate normal saccades well, but are challenged by clinical disorders because they often do not incorporate the specific anatomical and physiological substrates needed to model clinically important abnormalities. Historically, studies of saccadic abnormalities in patients have played a critical role in understanding the neural control of saccades because they provide information that complements basic research and thus restricts hypotheses to those that are biologically plausible. This review presents four examples of clinical disorders (slow saccades, interrupted saccades, high-frequency saccadic oscillations and macrosaccadic oscillations) that have provided insights into the neurobiology of saccades, have driven the development of new models, and have suggested an explanation or treatment for these disorders. We raise general questions for both scientists and clinicians that will assist in their efforts to understand the neural control of movement, improve diagnostic criteria and develop new treatments.

Brain↗
PubMed2006

Ocular motor indicators of executive dysfunction in fragile X and Turner syndromes.

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner syndrome, and 40 females with neither disorder who comprised the comparison group. Group differences emerged for both the fragile X and Turner syndrome groups, each relative to the comparison group: Females with fragile X had deficits in generating memory-guided saccades, predictive saccades, and saccades made in the overlap condition of a gap/overlap task. Females with Turner syndrome showed deficits in generating memory-guided saccades, but not during either the predictive saccade or gap/overlap task. Females with Turner syndrome, but not females with fragile X, showed deficits in visually guided saccades and anti-saccades. These findings indicate that different brain regions are affected in the two disorders, and suggest that different pathways lead to the similar cognitive phenotypes described for fragile X and Turner syndromes.

Adolescent↗
PubMed2006

Axis of eye rotation changes with head-pitch orientation during head impulses about earth-vertical.

The goal of this study was to assess how the axis of head rotation, Listing's law, and eye position influence the axis of eye rotation during brief, rapid head rotations. We specifically asked how the axis of eye rotation during the initial angular vestibuloocular reflex (VOR) changed when the pitch orientation of the head relative to Earth-vertical was varied, but the initial position of the eye in the orbit and the orientation of Listing's plane with respect to the head were fixed. We measured three-dimensional eye and head rotation axes in eight normal humans using the search coil technique during head-and-trunk (whole-body) and head-on-trunk (head-only) "impulses" about an Earth-vertical axis. The head was initially oriented at one of five pitch angles (30 degrees nose down, 15 degrees nose down, 0 degrees, 15 degrees nose up, 30 degrees nose up). The fixation target was always aligned with the nasooccipital axis. Whole-body impulses were passive, unpredictable, manual, rotations with peak-amplitude of approximately 20 degrees , peak-velocity of approximately 80 degrees /s, and peak-acceleration of approximately 1000 degrees /s2. Head-only impulses were also passive, unpredictable, manual, rotations with peak-amplitude of approximately 20 degrees , peak-velocity of approximately 150 degrees /s, and peak-acceleration of approximately 3000 degrees /s2. During whole-body impulses, the axis of eye rotation tilted in the same direction, and by an amount proportional (0.51 +/- 0.09), to the starting pitch head orientation (P < 0.05). This proportionality constant decreased slightly to 0.39 +/- 0.08 (P < 0.05) during head-only impulses. Using the head-only impulse data, with the head pitched up, we showed that only 50% of the tilt in the axis of eye rotation could be predicted from vectorial summation of the gains (eye velocity/head velocity) obtained for rotations about the pure yaw and roll head axes. Thus, even when the orientation of Listing's plane and eye position in the orbit are fixed, the axis of eye rotation during the VOR reflects a compromise between the requirements of Listing's law and a perfectly compensatory VOR.

Adult↗
PubMed2006

The effect of binocular eye position and head rotation plane on the human torsional vestibuloocular reflex.

We examined how the gain of the torsional vestibulo-ocular reflex (VOR) (defined as the instantaneous eye velocity divided by inverted head velocity) in normal humans is affected by eye position, target distance, and the plane of head rotation. In six normal subjects we measured three-dimensional (3D) eye and head rotation axes using scleral search coils, and 6D head position using a magnetic angular and linear position measurement device, during low-amplitude (approximately 20 degrees ), high-velocity (approximately 200 degrees/s), high-acceleration (approximately 4000 degrees /s2) rapid head rotations or 'impulses.' Head impulses were imposed manually and delivered in five planes: yaw (horizontal canal plane), pitch, roll, left anterior-right posterior canal plane (LARP), and right anterior-left posterior canal plane (RALP). Subjects were instructed to fix on one of six targets at eye level. Targets were either straight-ahead, 20 degrees left or 20 degrees right from midline, at distance 15 or 124 cm from the subject. Two subjects also looked at more eccentric targets, 30 degrees left or 30 degrees right from midline. We found that the vertical and horizontal VOR gains increased with the proximity of the target to the subject. Previous studies suggest that the torsional VOR gain should decrease with target proximity. We found, however, that the torsional VOR gain did not change for all planes of head rotation and for both target distances. We also found a dynamic misalignment of the vertical positions of the eyes during the torsional VOR, which was greatest during near viewing with symmetric convergence. This dynamic vertical skew during the torsional VOR arises, in part, because when the eyes are converged, the optical axes are not parallel to the naso-occipital axes around which the eyes are rotating. In five of six subjects, the average skew ranged 0.9 degrees -2.9 degrees and was reduced to <0.4 degrees by a 'torsional' quick-phase (around the naso-occipital axis) occurring <110 ms after the onset of the impulse. We propose that the torsional quick-phase mechanism during the torsional VOR could serve at least three functions: (1) resetting the retinal meridians closer to their usual orientation in the head, (2) correcting for the 'skew' deviation created by misalignment between the axes around which the eyes are rotating and the line of sight, and (3) taking the eyes back toward Listing's plane.

Adult↗
PubMed2005

Eye-position dependence of torsional velocity during step-ramp pursuit and transient yaw rotation in humans.

The time course of eye-position-dependent torsion during transient horizontal pursuit and yaw rotation was examined in seven normal human subjects. The stimuli consisted of step-ramp target motion (25, 40 degrees /s) and brief chair rotation (approximately 200 degrees /s(2) accelerated to 40 degrees /s) at three different vertical positions (center 0 degrees , up or down 15 degrees ). Three-dimensional eye movements were recorded with dual search coils. The kinematics of pursuit and the rotational vestibulo-ocular reflex (rVOR) were assessed by determining the tilt-angle slope, a measure of the variation of the axis of eye-velocity with vertical eye position. We found that the tilt-angle slope during pursuit was initially 0.4+/-0.07 (mean+/-95% confidence interval) and then gradually rose to 0.64+/-0.04, at about the time that the steady-state eye-velocity was reached. The rVOR began with a nearly head-fixed axis (0.08+/-0.04), appropriate for full retinal image stabilization, followed by a gradual increase of the tilt-angle slope to 0.31+/-0.02. Thus, differences between pursuit and the rVOR with respect to Listing's law can be seen from the onset of transient responses, although in both cases eye-position-dependent torsion increases with time. This temporal evolution of the axis of eye-velocity may involve the velocity-storage mechanism.

Adult↗
PubMed2005

Cerebellar disease alters the axis of the high-acceleration vestibuloocular reflex.

L. W. Schultheis and D. A. Robinson showed that the axis of the rotational vestibuloocular reflex (RVOR) cannot be altered by visual-vestibular mismatch ("cross-axis adaptation") when the vestibulocerebellum is lesioned. This suggests that the cerebellum may calibrate the axis of eye velocity of the RVOR under natural conditions. Thus we asked whether patients with cerebellar disease have alterations in the RVOR axis and, if so, what might be the mechanism. We used three-axis scleral coils to record head and eye movements during yaw, pitch, and roll head impulses in 18 patients with cerebellar disease and in a comparison group of eight subjects without neurologic disease. We found distinct shifts of the eye-velocity axis in patients. The characteristic finding was a disconjugate upward eye velocity during yaw. Measured at 70 ms after the onset of head rotation, the median upward gaze velocity was 15% of yaw head velocity for patients and <1% for normal subjects (P < 0.001). Upward eye velocity was greater in the contralateral (abducting) eye during yaw and in the ipsilateral eye during roll. Patients had a higher gain (eye speed/head speed) for downward than for upward pitch (median ratio of downward to upward gain: 1.3). In patients, upward gaze velocities during both yaw and roll correlated with the difference in anterior (AC) and posterior canal excitations, scaled by the respective pitch gains. Our findings support the hypothesis that upward eye velocity during yaw results from AC excitation, which must normally be suppressed by the intact cerebellum.

Acceleration↗
PubMed2005

Interaural translational VOR: suppression, enhancement, and cognitive control.

We investigated the influence of cognitive factors on the early response of the interaural translational vestibuloocular reflex (tVOR) in six normal subjects. Variables were prior knowledge of direction of head motion and the position of the fixation target relative to the head [head-fixed (HF) or space-fixed (SF)]. A manually driven device provided a step-like head translation (approximately 35 mm distance, peak acceleration, 0.6-1.3 g). Subjects looked at the SF or HF target located 15 cm in front of their heads in otherwise complete darkness. The testing paradigms were: random interleaving of SF and HF targets with unknown direction of head movement, known target location with random head direction (SFR or HFR), and known target location with known head direction (SFP or HFP). Timing was always unpredictable. A "gain" of the slow phase was calculated with respect to ideal performance (maintained fixation of the SF target, recorded/ideal eye velocity computed at time of peak head velocity). At such times, there were no significant differences in gain between HF and SF trials in the random condition; the average gain was approximately 36% of ideal. On the other hand, responses in the SFR and HFR conditions differed as early as 20 ms after the head began moving. Average gain was higher (0.43 +/- 0.11 vs. 0.34 +/- 0.14; means +/- SD, P < 0.05) for each subject in the SFR than the HFR condition. For SFP and HFP, the responses differed from the onset of head motion. Average slow-phase gain was higher (0.49 +/- 0.12 vs. 0.31 +/- 0.12, P < 0.02) for each subject in SFP than in HFP. The timing of corrective saccades during the tVOR was also influenced by cognitive factors. Visual error signals seemed to be more important for triggering saccades in HF trials, whereas preprogramming, probably based on labyrinthine information, seemed to be more important in SF trials. Simulations showed that the changes in slow-phase gain with cognition could be reproduced with simple parametric adjustments of the gain of activity from otolith afferents and suggest that higher-level cognitive control of the VOR could occur as early as the synapse of peripheral afferents on neurons in the vestibular nuclei, either directly from higher level centers or via the cerebellum. In sum, the tVOR-both in its slow-phase response and the saccadic corrections-is subject to "higher-level" cognitive influences including knowledge of where the line of sight must point during head motion and the impending direction of head motion.

Acceleration↗
PubMed2005

Ocular oscillations generated by coupling of brainstem excitatory and inhibitory saccadic burst neurons.

The human saccadic system is potentially unstable and may oscillate if the burst neurons, which generate saccades, are not inhibited by omnipause neurons. A previous study showed that combined saccade vergence movements can evoke oscillations in normal subjects. We set out to determine: 1) whether similar oscillations can be recorded during other paradigms associated with inhibition of omnipause neurons; 2) whether lesions of the fastigial nuclei disrupt such oscillations; and 3) whether such oscillations can be reproduced using a model based on the coupling of excitatory and inhibitory burst neurons. We recorded saccadic oscillations during vergence movements, combined saccade-vergence movements, vertical saccades, pure vergence and blinks in three normal subjects, and in a patient with saccadic hypermetria due to a surgical lesion affecting both fastigial nuclei. During combined saccade-vergence, normal subjects and the cerebellar patient developed small-amplitude (0.1 - 0.5 degrees), high-frequency (27-35 Hz), conjugate horizontal saccadic oscillations. Oscillations of a similar amplitude and frequency occurred during blinks, pure vergence and vertical saccades. One normal subject could generate saccadic oscillations voluntarily (approximately 0.7 degrees amplitude, 25 Hz) during sustained convergence. Previous models proposed that high-frequency eye oscillations produced by the saccadic system (saccadic oscillations), occur because of a delay in a negative feedback loop around high-gain, excitatory burst neurons in the brainstem. The feedback included the cerebellar fastigial nuclei. We propose another model that accounts for saccadic oscillations based on 1) coupling of excitatory and inhibitory burst neurons in the brainstem and 2) the hypothesis that burst neurons show post-inhibitory rebound discharge. When omnipause neurons are inhibited (as during saccades, saccade-vergence movements and blinks), this new model simulates oscillations with amplitudes and frequencies comparable to those in normal human subjects. The finding of saccadic oscillations in the cerebellar patient is compatible with the new model but not with the recent models including the fastigial nuclei in the classic negative-feedback loop model. Our model proposes a novel mechanism for generating oscillations in the oculomotor system and perhaps in other motor systems too.

Adult↗
PubMed2005

The neuro-ophthalmology of multiple sclerosis.

Multiple sclerosis (MS) is the most common disabling neurological disease in young people. Most CNS lesions involve neuroanatomically non-eloquent zones that often do not result in symptomatic complaints. By contrast, tissue-injury mechanisms involving inflammatory demyelination can involve more eloquent sites, such as the optic nerve and brainstem, which can correspondingly produce the development of well recognised syndromes such as optic neuritis and internuclear ophthalmoplegia, respectively. In this review we discuss the broad landscape of abnormalities that affect the afferent visual system and the ocular motor apparatus, and emphasise relevant features, the recognition and treatment of which are of importance to general neurological practice. The commonness of visual sensory and eye movement abnormalities in MS highlights the importance of understanding the principles addressed in this review.

Humans↗
PubMed2005

Binocular coordination in fore/aft motion.

Stabilization of images on the fovea during either fore/aft translation of a subject or fore/aft movement of a visual target in front of a stationary observer imposes complex geometrical requirements that depend upon the eccentricity of the object of interest with respect to the eyes. Each eye needs to be rotated independently with varying proportions of conjugate (version) and disconjugate (vergence) eye movements to maintain fixation of the target. Here, we describe binocular coordination in the early response to translational movements of normal subjects along their naso-occipital axis. We recorded the responses evoked by small (about 4 cm), abrupt (about 0.7 g), fore/aft translations in four normal subjects while they viewed a near target. In the forward and backward starting positions the target was 15 or 10.5 cm away, respectively. Each subject was tested with the target centered between the eyes, aligned on the right eye, and placed to the right of the right eye by approximately 3 cm. The three conditions differed only in the lateral eccentricity of the target, yet the geometrical requirements for image stabilization are very different: pure vergence, one eye still, or mostly version. We found that the eye-movement responses closely matched what was needed for visual stabilization of the target, though responses to stimuli calling for divergence were less accurate than those for convergence. The latency of these responses ranged from 40 to 65 ms and achieved about 80% of the ideal response by 90 to 100 ms after the onset of the stimulus. Next, we asked whether these eye movements were generated by the vestibular system or by high-level strategies for image stabilization, such as pursuit. Thus, in a second set of experiments we used the mean profile of fore\aft body motion computed for each subject to drive a small visual target across the same distances and in the same eccentricities used during body translations. We found that visually driven responses had longer latencies (by at least 80 ms, ranging from 144 to 155 ms) and slower dynamics (with significantly lower peak eye velocities), highlighting the different subsystems producing the two types of responses. Saccades were also an important component of the response to both visual and vestibular stimuli, less frequent during the centered-target configuration and more frequent during viewing of eccentric targets. Visual stimuli evoked saccadic corrections more often and at shorter latencies than did vestibular stimuli. Both smooth and saccadic eye movements were appropriately disconjugate and their pattern depended on whether the eyes were converging or diverging.

Adult↗
PubMed2005

Gaze position corrective eye movements in normal subjects and in patients with vestibular deficits.

Eye movements in response to high-acceleration head rotations (thrusts) in the horizontal plane from patients with unilateral (UVD) or bilateral vestibular loss (BVD) were recorded. The rapid, gaze-position corrections (GPCs) that appeared when vestibulo-ocular reflex (VOR) slow phases were undercompensatory were characterized. For comparison, eye movements from normal subjects who were asked to generate saccades in the direction opposite head rotation (in the same direction as slow phases) were recorded. This normal-subject model produced responses with spatial and temporal characteristics similar to those from GPCs in patients as follows: When head rotations were generated actively, compared with passively, gaze-position errors and corresponding GPCs were smaller and occurred earlier. During passively generated head thrusts, GPCs still occurred when head rotations were made in total darkness, though their accuracy decreased as the requirement for maintaining gaze on a specific location in space was relaxed. Time of onset of GPCs was not rigidly tied to head kinematics (peak velocity or peak acceleration). Speeds of GPCs, however, were lower than speeds of similar-sized, head-fixed saccades. Finally, during passive and active head thrusts in patients, sustained, high-frequency (20 to 30 Hz) oscillations that appeared as tiny saccades were occasionally observed, one immediately following the other, resembling a compensatory slow-phase response. Taken together, the results suggest that one strategy for overcoming a VOR deficit is to enlist the saccadic system to produce an oculomotor response that is required to compensate for head rotation. This response may come in the form of high-velocity GPCs or smaller-amplitude oscillations.

Accommodation, Ocular↗
PubMed2005

Asymmetry of the pitch vestibulo-ocular reflex in patients with cerebellar disease.

Responses to pitch head impulses were measured in 15 patients with cerebellar degeneration and downbeat nystagmus and in 5 control subjects, using three-axis search coils. For each subject, response gains were calculated as (1) the ratio of instantaneous vertical eye velocity to pitch head velocity (at 30 ms and at 70 ms into the response), and (2) the ratio of peak eye velocity to peak head velocity. Gains varied more widely among patients. When calculated at 70 ms and using peak values, patients had higher gains for downward pitch, and normal subjects had symmetric gains. At 30 ms, gains were more symmetric in patients, but at that point control subjects actually had lower gains for downward pitch. Thus, the pitch gain ratio (ratio of downward gain to upward gain) was consistently greater in patients than in normal subjects. Because downward impulses were generally faster, eye velocities during downward and upward pitch for equivalent head speeds were also compared. Again, patients had higher gains for downward pitch. These results are consistent with the authors' hypothesis that cerebellar disease results in a higher sensitivity of anterior than posterior semicircular canal pathways, perhaps through loss of inhibition from the flocculus/paraflocculus complex on anterior canal secondary neurons in the vestibular nuclei. The pitch gain asymmetry was larger than, and did not correlate with, the velocity of spontaneous upward drift. This supports the notion that other mechanisms are likely to contribute to downbeat nystagmus in these patients.

Adult↗
PubMed2005

Niemann-Pick type C disease in two affected sisters: ocular motor recordings and brain-stem neuropathology.

Two sisters with Niemann-Pick disease type C were examined: the brain in one sister, who had died, was examined, and eye movements in the other, surviving sister were recorded. Ocular motor recordings showed marked slowing of vertical saccades with relative sparing of horizontal saccades, pursuit, and the vestibulo-ocular reflex. Neuropathological findings included glial fibrillary lesions in the area of the posterior commissure and neuronal loss in the rostral interstitial nucleus of the MLF with preservation of the interstitial nucleus of Cajal and ocular motor complex. These neuropathologic findings correlate well with our current understanding of the anatomy and physiology of the supranuclear control of vertical gaze.

Adult↗
PubMed2004

Influence of orientation of exiting wire of search coil annulus on torsion after saccades.

PURPOSE: Research has shown that the orientation of the exiting wire from a scleral search coil (nasal in the original coil, inferior in the modified coil) influences the pattern of torsion associated with blinks, presumably due to the upper eyelid touching the wire. The present study was conducted to investigate whether coil wire orientation also influences the pattern of torsion during fixation after saccades and consequently influences parameters that determine Listing's plane and Donders' law. METHODS: Three-axis, binocular eye rotations were recorded in three healthy human subjects looking at an array of small light-emitting diodes at a 124-cm distance. They made predominantly vertical or predominantly horizontal saccades (5-40 degrees, amplitude) at three (0 +/- 20 degrees) azimuths, or elevations. RESULTS: With the modified coil, the horizontal component of Listing's primary position was similar for horizontal (mean temporal deviation, 2.9 degrees) and vertical (3.3 degrees) saccades. With the original coil, the horizontal component of primary position was more temporal after horizontal (12.3 degrees) than vertical (6.1 degrees) saccades. The vertical component of primary position was similar with both coils after horizontal and vertical saccades. Listing's plane was thinner with the modified coil after horizontal (standard deviation of torsion from a plane of 0.71 degrees vs. 1.31 degrees) and vertical (0.84 degrees vs.1.67 degrees) saccades. The standard deviation of torsion at a given eye position (Donders' law) was smaller with the modified coil. CONCLUSIONS: Measures of torsion after horizontal or vertical saccades depend on whether the coil wire exits nasally or inferiorly and, with the original coil, whether the saccades are horizontal or vertical. Lid contact may account for these potential artifacts. They must be appreciated in the interpretation of three-dimensional search coil recordings, using the scleral annulus.

Adult↗
PubMed2004

Central and peripheral visual interactions in disparity-induced vergence eye movements: I. Spatial interaction.

PURPOSE: To evaluate the interaction between central and peripheral disparities in the initiation of vergence eye movements. METHODS: Eye movements were recorded in eight normal subjects using an infrared limbus tracker. Three-dimensional visual stimuli were back projected onto a tangent screen by using two liquid crystal display (LCD) projectors through crossed polarizers. The central target was a vertical bar, which always jumped from 2 to 1 m. The peripheral target was a random-dot pattern that jumped from 2 to 0.75, 1, or 1.5 m (near planes), 2 m (no change), or 3 m (far plane) simultaneously with the central target jump. Latency, amplitude at 150 ms, and average amplitude over 1 to 2 seconds after vergence onset; peak velocity; and the main-sequence relationship of the initial vergence response were calculated. How far the central target appeared to jump was scored subjectively. RESULTS: In half of the subjects, there was a clear effect of the peripheral disparity on the dynamics of the vergence response to the central disparity. The amplitude of vergence at 150 ms, as an index of open-loop gain, was significantly greater when the peripheral target moved closer, but steady state amplitude (average during 1-2 seconds) did not change, and the vergence latency was significantly greater when the peripheral target jumped away. There was no obvious relationship between the perceived amount of movement of the central target and the parameters of the dynamic properties of the vergence response. CONCLUSIONS: Peripheral disparity can modulate the dynamics of the initial vergence response to a central disparity and is probably independent of the perception of motion in depth.

Adult↗
PubMed2003

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↗