Eye Drift Velocity Research Articles

Prevalence and Characteristics of Physiological Gaze-Evoked and Rebound Nystagmus: Implications for Testing Their Pathological Counterparts.

Objective: Cerebellar diseases frequently affect the ocular motor neural velocity-to-position integrator by increasing its leakiness and thereby causing gaze-evoked nystagmus (GEN) and rebound nystagmus (RN). Minor leakiness is physiological and occasionally causes GEN in healthy humans. We aimed to evaluate the characteristics of GEN/RN in healthy subjects for better differentiation between physiological and pathological GEN/RN.Methods: Using video-oculography, eye position was measured in 14 healthy humans at straight ahead eye position before and after, and during 30 s of ocular fixation at 4 horizontal eccentric targets between 30° and 45°. We determined the eye drift velocity and the prevalence of nystagmus before/during/after eccentric fixation.Results: Eye drift velocities during (range: 0.62 ± 0.53°/s to 1.78 ± 0.69°/s) and after eccentric gaze (range: 0.28 ± 0.52°/s to 1.48 ± 1.02°/s) increased with the amount of gaze eccentricity (30°-45°). During continuous eccentric gaze, eye drift velocities decreased by 0.41 ± 0.18°/s at 30°, and 0.84 ± 0.38°/s at 45° gaze eccentricity. GEN was elicited in 71% of subjects at 30° gaze eccentricity. Twenty-one percent showed RN thereafter. This prevalence increased to 100% (GEN)/72% (RN) at 45° gaze eccentricity. RN found after 30° gaze eccentricity was of low velocity (0.82 ± 0.21°/s) and occurred after minor drift velocity decrease during prior eccentric gaze (0.43 ± 0.15°/s).Conclusion: GEN and RN should be tested using horizontal gaze eccentricities of <30°, since most healthy subjects physiologically show GEN and RN at higher eccentricities. In case of an uncertain result, both the reduction of eye drift velocity during eccentric gaze and the velocity of RN can be analyzed to distinguish physiological from pathological nystagmus.

Asymmetry in Gaze-Holding Impairment in Acute Unilateral Ischemic Cerebellar Lesions Critically Depends on the Involvement of the Caudal Vermis and the Dentate Nucleus.

Stabilizing the eyes in space when looking at a target is provided by a brainstem/cerebellar gaze-holding network, including the flocculus/paraflocculus complex (non-human primate studies) and the caudal vermis, biventer, and inferior semilunar lobule (human studies). Previous research suggests that acute lateralized cerebellar lesions preferentially lead to gaze-evoked nystagmus (GEN) on ipsilesional gaze. Here, we further characterize the effect of unilateral cerebellar lesions on gaze-holding and hypothesize that the side-specific magnitude of gaze-holding impairment depends on the lesion location. Nine patients (age range = 31-62 years) with acute/subacute (≤ 10 days old) MRI-confirmed unilateral cerebellar stroke were included. Horizontal gaze holding was quantified while looking at a slowly moving (0.5°/s) flashing target (gaze angle = ±40°). Asymmetry in eye-drift velocity was calculated and compared with the different MRI patterns of cerebellar lesions. Individual peak eye-drift velocities (range = 1.7-8.8°/s) occurred at the most eccentric eye positions (gaze angle = 28-38°). We found significantly asymmetric eye-drift velocity (EDV) in eight out of nine patients. The four patients with MRI-confirmed involvement of the caudal vermis and the dentate nucleus all presented with ipsilesionally-predominant EDV, while in the five patients with lesions restricted to the cerebellar hemisphere, EDV was stronger on contralesional gaze in three out of four found with an asymmetric EDV. Involvement of the caudal vermis and the dentate nucleus is critical for determining the directional GEN asymmetry in unilateral cerebellar lesions. Thus, our findings support the occurrence of GEN without floccular/parafloccular lesions and suggest that the EDV asymmetry in relation to the side of the lesion provides information about the involvement of specific structures.

Cerebellar Rebound Nystagmus Explained as Gaze-Evoked Nystagmus Relative to an Eccentric Set Point: Implications for the Clinical Examination.

A brain stem/cerebellar neural integrator enables stable eccentric gaze. Cerebellar loss-of-function can cause an inability to maintain gaze eccentrically (gaze-evoked nystagmus). Moreover, after returning gaze to straight ahead, the eyes may drift toward the prior eye position (rebound nystagmus). Typically, gaze-evoked nystagmus decays during continuously held eccentric gaze. We hypothesized this adaptive behavior to be prerequisite for rebound nystagmus and thus predicted a correlation between the velocity decay of gaze-evoked nystagmus and the initial velocity of rebound nystagmus. Using video-oculography, eye position was measured in 11 patients with cerebellar degeneration at nine horizontal gaze angles (15° nasal to 25° temporal) before (baseline), during, and after attempted eccentric gaze at ± 30° for 20s. We determined the decrease of slow-phase velocity at eccentric gaze and the slow-phase velocity of the subsequent rebound nystagmus relative to the baseline. During sustained eccentric gaze, eye drift velocity of gaze-evoked nystagmus decreased by 2.40 ± 1.47°/s. Thereafter, a uniform change of initial eye drift velocity relative to the baseline (2.40 ± 1.35°/s) occurred at all gaze eccentricities. The velocity decrease during eccentric gaze and the subsequent uniform change of eye drift were highly correlated (R2 = 0.80, p < 0.001, slope = 1.09). Rebound nystagmus can be explained as gaze-evoked nystagmus relative to a set point (position with least eye drift) away from straight-ahead eye position. To improve detection at the bedside, we suggest testing rebound nystagmus not at straight-ahead eye position but at an eccentric position opposite of prior eccentric gaze (e.g., 10°), ideally using quantitative video-oculography to facilitate diagnosis of cerebellar loss-of-function.

Non-linearity in gaze holding: Experimental results and possible mechanisms.

Cerebellar impairment may cause deficits in horizontal gaze holding, leading to centrifugal gaze-evoked nystagmus during fixation of eccentric targets. Healthy individuals show a weak drift leading to physiological nystagmus only at large gaze angles. These drifts are due to imperfect memory of the neural circuitry generating the eye position signals by integration of velocity signals. The cerebellum plays a crucial role in reducing the "leakiness" of this neural integrator. This neural integrator has been traditionally modeled as a first order low-pass filter, implying a linear relation between drift velocity and eye eccentricity. Evidences of a non-linear behavior, however, can be found in the literature. In a recent series of papers we showed that the eye drift velocity (V) can be descriptively modeled as a tangent function of gaze eccentricity (P) with the following equation: V=k2/k1tan(k1P). Notably, the two parameters have distinct roles: k1 regulates the rate of compression of the tangent, exclusively determining the non-linearity; k2 is a pure scaling factor. This descriptive model robustly fitted the data of healthy individuals both at baseline (n=50) and following transient cerebellar impairment induced by controlled amounts of alcohol [blood alcohol content 0.06% (n=15) and 0.1% (n=15)] and of patients with chronic cerebellar impairment of various origin (n=20). Interestingly, alcohol selectively changed the scaling factor k2, evidencing that an overall, transient cerebellar impairment does not impact the non-linear behavior. Patients with cerebellar degeneration, on the other hand, showed a change in both k1 and k2, implying a role of the cerebellum in limiting the range of eye positions where the non-linearity becomes relevant. Non-linearity has been reported in literature for both the neural integrator and the eye plant. While previous models using a neural network attempted to reproduce the non-linear behavior of the brainstem, we propose a block diagram reproducing the observed PV tangent relation by introducing a position dependency in the parameters of the cerebellar feedback loop.

Gaze-evoked nystagmus induced by alcohol intoxication.

The cerebellum is the core structure controlling gaze stability. Chronic cerebellar diseases and acute alcohol intoxication affect cerebellar function, inducing, among others, gaze instability as gaze-evoked nystagmus. Gaze-evoked nystagmus is characterized by increased centripetal eye-drift. It is used as an important diagnostic sign for patients with cerebellar degeneration and to assess the 'driving while intoxicated' condition. We quantified the effect of alcohol on gaze-holding using an approach allowing, for the first time, the comparison of deficits induced by alcohol intoxication and cerebellar degeneration. Our results showed that alcohol intoxication induces a two-fold increase of centripetal eye-drift. We establish analysis techniques for using controlled alcohol intake as a model to support the study of cerebellar deficits. The observed similarity between the effect of alcohol and the clinical signs observed in cerebellar patients suggests a possible pathomechanism for gaze-holding deficits. Gaze-evoked nystagmus (GEN) is an ocular-motor finding commonly observed in cerebellar disease, characterized by increased centripetal eye-drift with centrifugal correcting saccades at eccentric gaze. With cerebellar degeneration being a rare and clinically heterogeneous disease, data from patients are limited. We hypothesized that a transient inhibition of cerebellar function by defined amounts of alcohol may provide a suitable model to study gaze-holding deficits in cerebellar disease. We recorded gaze-holding at varying horizontal eye positions in 15 healthy participants before and 30min after alcohol intake required to reach 0.6‰ blood alcohol content (BAC). Changes in ocular-motor behaviour were quantified measuring eye-drift velocity as a continuous function of gaze eccentricity over a large range (±40deg) of horizontal gaze angles and characterized using a two-parameter tangent model. The effect of alcohol on gaze stability was assessed analysing: (1) overall effects on the gaze-holding system, (2) specific effects on each eye and (3) differences between gaze angles in the temporal and nasal hemifields. For all subjects, alcohol consumption induced gaze instability, causing a two-fold increase [2.21 (0.55), median (median absolute deviation); P=0.002] of eye-drift velocity at all eccentricities. Results were confirmed analysing each eye and hemifield independently. The alcohol-induced transient global deficit in gaze-holding matched the pattern previously described in patients with late-onset cerebellar degeneration. Controlled intake of alcohol seems a suitable disease model to study cerebellar GEN. With alcohol resulting in global cerebellar hypofunction, we hypothesize that patients matching the gaze-holding behaviour observed here suffered from diffuse deficits in the gaze-holding system as well.

Visual and non-visual motion information processing during pursuit eye tracking in schizophrenia and bipolar disorder.

Despite many reports on visual processing deficits in psychotic disorders, studies are needed on the integration of visual and non-visual components of eye movement control to improve the understanding of sensorimotor information processing in these disorders. Non-visual inputs to eye movement control include prediction of future target velocity from extrapolation of past visual target movement and anticipation of future target movements. It is unclear whether non-visual input is impaired in patients with schizophrenia. We recorded smooth pursuit eye movements in 21 patients with schizophrenia spectrum disorder, 22 patients with bipolar disorder, and 24 controls. In a foveo-fugal ramp task, the target was either continuously visible or was blanked during movement. We determined peak gain (measuring overall performance), initial eye acceleration (measuring visually driven pursuit), deceleration after target extinction (measuring prediction), eye velocity drifts before onset of target visibility (measuring anticipation), and residual gain during blanking intervals (measuring anticipation and prediction). In both patient groups, initial eye acceleration was decreased and the ability to adjust eye acceleration to increasing target acceleration was impaired. In contrast, neither deceleration nor eye drift velocity was reduced in patients, implying unimpaired non-visual contributions to pursuit drive. Disturbances of eye movement control in psychotic disorders appear to be a consequence of deficits in sensorimotor transformation rather than a pure failure in adding cognitive contributions to pursuit drive in higher-order cortical circuits. More generally, this deficit might reflect a fundamental imbalance between processing external input and acting according to internal preferences.

Gaze holding deficits discriminate early from late onset cerebellar degeneration.

The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocity-to-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle=±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities≥20°. Pure scaling was most frequently observed (n=10/18), followed by pure shape-changing (n=4/18) and a mixed pattern (n=4/18). Pure shape-changing patients were significantly (p=0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early- from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined.

Spontaneous eye movements in goldfish: oculomotor integrator performance, plasticity, and dependence on visual feedback

To quantify performance of the goldfish oculomotor neural integrator and determine its dependence on visual feedback, we measured the relationship between eye drift-velocity and position during spontaneous gaze fixations in the light and in the dark. In the light, drift-velocities were typically less than 1 deg/s, similar to those observed in humans. During brief periods in darkness, drift-velocities were only slightly larger, but showed greater variance. One hour in darkness degraded fixation-holding performance. These findings suggest that while visual feedback is not essential for online fixation stability, it may be used to tune the mechanism of persistent neural activity in the oculomotor integrator.

Vertical eye position control in darkness: orbital position and body orientation interact to modulate drift velocity.

How stable is vertical eye-in-head position control in darkness when no visual targets are present? We evaluated this while varying both body-in-space orientation and eye-in-orbit position in six subjects who were free from oculomotor/vestibular disease. Vertical eye movements were monitored using a CCD-video tracking system, and results were confirmed on one subject with the magnetic search coil. Three body orientations were used: (1) seated upright; (2) supine; and (3) prone. In each of these body orientations starting eye-in-orbit position was varied in quasi-random order from -20 to +20 deg, while vertical eye drift was monitored for a 90 sec period at each position. Subjects were instructed to hold their eyes as steady as possible. The relationship between body orientation/eye position and vertical eye drift velocity was examined using a linear regression technique. In contrast to prior clinical reports, normals exhibit a vertical nystagmus/drift in darkness. Moreover, slow-phase eye velocity was found to be dependent on eye-in-orbit position in the upright and supine body orientations. This pattern of eye drift mirrors Alexander's Law, with significantly increased drift velocities when subjects looked in the direction of their re-centering saccades (P < 0.05 or better). Body-in-space orientation also modulated the eye drift velocity, with significant differences in rate of eye drift (P < 0.05 or better) between extremes of body orientation (supine and prone) for five out of six subjects. The stability of the vertical oculomotor control system in the absence of visual input is strongly affected by body-in-space orientation and eye-in-orbit position: manipulating either of these variables results in non-random patterns of drift. These results are discussed using a multiple-input model of vertical eye-in-head position control.