Oculomotor function in Wernicke-Korsakoff's syndrome: II. Smooth pursuit eye movements

Smooth pursuit eye movements were studied in three patients with alcoholic Korsakoff's syndrome, one with Wernicke's encephalopathy, and an age-matched control. Horizontal smooth pursuit eye movements were abnormal in all patients: peak eye velocity and the ability to sustain smooth eye velocity were reduced. Also, smooth pursuit gain began to decrease at relatively low target velocities (i.e., 8-10 degrees). These data demonstrate a severe disturbance in smooth pursuit function long after the clinically apparent oculomotor abnormalities have passed.     

Dependence of impaired eye tracking on deficient velocity discrimination in schizophrenia

BACKGROUND: Abnormal smooth pursuit eye movements have been found in many schizophrenic patients and in about 40% of their first-degree biological relatives. A velocity discrimination deficit has also been demonstrated in schizophrenic patients. In this study, we address the relation between deficient velocity discrimination and impaired smooth pursuit eye movements, inasmuch as the brain regions responsible for processing velocity signals are implicated in generating and maintaining smooth pursuit. METHODS: Horizontal eye movements of 15 schizophrenic patients and 8 normal controls were recorded in response to sine wave (predictable) and step-ramp (nonpredictable) targets. Smooth pursuit eye movements were assessed during both the initiation and maintenance periods. Correlations were computed between measures of smooth pursuit (qualitative rating, peak gain, saccade frequency, and initial acceleration) and contrast sensitivity for velocity discrimination. RESULTS: Contrast sensitivity for fine velocity discrimination was significantly correlated both with initial acceleration of smooth pursuit and with peak gain, but was not significantly correlated with saccade frequency and qualitative ratings of pursuit integrity. No significant correlations were found within the normal control group. CONCLUSION: Deficient processing of velocity information seems to be one component that contributes to a dysfunction in the initiation and maintenance of smooth pursuit in schizophrenia.     

Dissociation of smooth pursuit and vestibulo-ocular reflex cancellation in SCA-6

OBJECTIVE: To study gaze in SCA-6 patients during pursuit and passive whole-body rotation. BACKGROUND: Smooth pursuit and vestibularly induced eye movements interact to maintain the accuracy of eye movements in space (i.e., gaze). Previous studies have implicated the cerebellum, particularly the floccular lobe and dorsal vermis, in the control of gaze velocity during pursuit and vestibulo-ocular reflex (VOR) cancellation. SCA-6 has recently been identified genetically and characterized as pure cerebellar ataxia that affects the cerebellar cortex selectively. METHODS: Using infrared oculography, eye movements of five SCA-6 patients and five age-matched normal control subjects were recorded during sinusoidal pursuit and passive whole-body rotation in the horizontal plane (amplitude, +/- 10 deg; frequency, 0.2 Hz). Eye and gaze gain (eye and gaze velocity/stimulus velocity) were calculated after deleting saccades. RESULTS: Eye gain of all SCA-6 patients during pursuit was significantly lower than those of the control subjects (mean +/- SD, 0.26+/-0.06 versus 0.91+/-0.07). In contrast, eye gain of the patients was not significantly different from that of the control subjects either during VOR cancellation, when the subjects tracked a target that moved with the same amplitude and phase, like a chair (0.21+/-0.05 versus 0.12+/-0.07), or during visually enhanced VOR (x1), when the target remained stationary in space (0.85+/-0.06 versus 0.95+/-0.05). Moreover, there was no significant difference in mean VOR gain in total darkness between the two groups. Gaze gain of patients (0.26+/-0.06 versus 0.81+/-0.06) but not control subjects (0.91+/-0.07 versus 0.88+/-0.08), was significantly different during pursuit and VOR cancellation. CONCLUSION: SCA-6 patients show dissociation in the control of gaze tracking during smooth pursuit and VOR cancellation.     

A quantitative analysis of saccades and smooth pursuit during visual pursuit tracking. A comparison of schizophrenics with normals and substance abusing controls.

The eye movements of schizophrenic patients are characterized by decreased smooth pursuit gain and an increased frequency of saccades. However, the nature of these saccades and their function during smooth pursuit has not been clearly defined. To address this issue we examined the eye movements of 22 schizophrenic patients, 20 substance abusing patients (primarily alcohol; some with concomitant cocaine and/or cannabis abuse), and 17 normal controls during a visual pursuit task using infra-red oculography. A computerized pattern recognition algorithm divided pursuit eye movements into two basic components: smooth pursuit and saccadic eye movements. The algorithm also determined eye position error and velocity error before and after each saccade. Schizophrenic patients had lower smooth pursuit gain (p less than 0.02) and made more saccades during smooth pursuit (p less than 0.02) than either comparison group. When saccades were assigned to subcategories based on direction and position error, only the frequency of 'catch-up' saccades differentiated schizophrenic patients from the comparison groups (p less than 0.05). Smooth pursuit gain was negatively correlated with saccadic frequency among all three subject groups. Eye velocity preceding saccades was significantly lower among the schizophrenic patients, but pre or post saccadic position error did not differ among the three groups. Discrete analysis of the fine structure of visual pursuit tracking may lead to a better understanding of eye movement abnormalities in schizophrenia.     

Effects of stimulus velocity and acceleration on smooth pursuit in motor neuron disease

Sinusoidal smooth pursuit eye movements were evaluated in 11 normals, five moderately and four severely affected motor neuron disease (MND) patients, using two target amplitudes and a range of frequencies. This enabled us to examine separately the effects of peak target velocity and acceleration on pursuit gain. Moderately affected patients showed an acceleration, but not a velocity saturation; severely impaired patients' performance declined with increased velocity. Smooth pursuit eye movements are thus impaired in MND, but the nature of this pursuit deficit is complex and changes with the progression of the disease.     

The effects of tobacco smoking on smooth pursuit eye movements

It has recently been shown that tobacco smoking in normal human subjects induces a transient primary-position upbeat nystagmus. We studied the effects of tobacco smoking on smooth pursuit eye movements and found defects in both vertical and horizontal tracking during the first 5 minutes after smoking one cigarette. The smooth pursuit defect consisted of a reduction in upward tracking velocity and the superposition of saccadic square-wave jerks on both vertical and horizontal tracking eye movements. The degree of impairment in upward smooth pursuit correlated with the intensity of tobacco-induced nystagmus present when recording in darkness. We suggest that these alterations are due to summation of nystagmus on normal tracking eye movements rather than primary defects in the smooth pursuit system.     

Eye movement abnormalities correlate with genotype in autosomal dominant cerebellar ataxia type I

We compared horizontal eye movements (visually guided saccades, antisaccades, and smooth pursuit) in control subjects (n = 14) and patients with three forms of autosomal dominant cerebellar ataxias type I: spinocerebellar ataxias 1 and 2 (SCA1, n = 11; SCA2, n = 10) and SCA3/Machado-Joseph disease (MJD) (n = 16). In SCA1, saccade amplitude was significantly increased, resulting in hypermetria. The smooth pursuit gain was decreased. In SCA2, saccade velocity was markedly decreased. The percentage of errors in antisaccades was greatly increased and was significantly correlated with age at disease onset. In addition, a correlation between smooth pursuit gain and the number of trinucleotide repeats was found. In SCA3, gaze-evoked nystagmus was often present as was saccade hypometria and smooth pursuit gain was markedly decreased. Three major criteria, saccade amplitude, saccade velocity, and presence of gaze-evoked nystagmus, permitted the correct assignment of 90% of the SCA1, 90% of the SCA2, and 93% of the patients with SCA3 to their genetically confirmed patient group and, therefore, may help orient diagnose of SCA1, SCA2, and SCA3 at early clinical stages of the diseases.     

Effect of typical antipsychotic medications and clozapine on smooth pursuit performance in patients with schizophrenia.

The effect of typical neuroleptic drugs or clozapine on smooth pursuit eye movements was tested in 13 patients with schizophrenia or schizoaffective disorder with a repeated measures design. Nineteen normal control subjects were also studied. Compared with controls, patients in the unmedicated state had low smooth pursuit gain, had a higher rate of corrective catch-up saccades, and tended to spend less time engaged in the tracking task. The patients did not significantly differ from controls on catch-up saccade amplitude, square wave jerk rate, or anticipatory saccade rate. Medication with clozapine, but not typical neuroleptics, was associated with an increase in median catch-up saccade amplitude. Number of days on clozapine and clozapine dose both correlated significantly with a worsening of oculomotor performance. No effect of medication with typical neuroleptics was found, although there was some evidence suggesting that such an affect may occur after more prolonged treatment.     

Subdural applications of NO scavenger or NO blocker to the cerebellum depress the adaptation of monkey post-saccadic smooth pursuit eye movements

We examined pharmacologically whether cerebellar long-term depression (LTD) may play a role in the adaptation of smooth pursuit eye movements in two Macaca fuscata, which were trained to pursue a target moving in the horizontal plane in a 3 degrees step-10 deg/s ramp mode. The monkeys showed small catch-up saccades followed by 6-8 deg/s post-saccadic pursuit movements. Adaptation of the post-saccadic pursuit velocity was induced by repetition of acceleration of the target to 20 deg/s after the catch-up saccades. Injections of 0.1 mM hemoglobin or 20 mM NG-monomethyl-L-arginine solution into the subdural space above the paraflocculus-flocculus scarcely affected the post-saccadic pursuit velocity, but markedly depressed its adaptation. These observations suggest that cerebellar LTD may underlie the adaptation of smooth pursuit.     

Sensitivity of eye movement registration and visual evoked potentials in evaluation of therapy in patients with multiple sclerosis.

A major problem in the evaluation of multiple sclerosis (MS) treatment protocols is the lack of an objective and reliable marker of disease activity. In 24 MS patients who were treated with high doses of intravenous methylprednisolone because of an acute relapse or progressive disease the clinical improvement (as measured by the Kurtzke expanded disability status scale) was compared with two paraclinical parameters, i.e. visual evoked potentials (VEP) and the registration of saccadic and smooth pursuit eye movements. After treatment a significant clinical improvement was found in 50% of the patients. The registration of eye movements revealed a significant improvement in 83% of the patients, the VEP in 21%. It is demonstrated that especially the registration of eye movements can have an important application as an objective and sensitive method in the assessment of neurological functions during MS treatment protocols.     

Abnormalities of smooth eye and head movement control in parhson's disease

The control of horizontal head and eye movements was examined in 13 nondemented patients with Parkinson's disease (PD) of mild to moderate severity. During pursuit of single-frequency sine waves, smooth component eye velocity was lower in the PD group at frequencies of 1.2 Hz and above; but the differences in overall eye displacement were even greater, indicating an impaired ability to generate catch-up saccades at high frequencies. A corresponding deficit in saccadic performance was observed during a high-frequency saccadic tracking task where predictive saccades of reduced gain and variable timing were generated. During pursuit of pseudo-random target motion with varying degrees of predictability, small differences in smooth component eye velocity were observed, but prediction was otherwise well preserved in the patient group. Vestibulo-ocular reflex (VOR) suppression was also normal during head-free pursuit. No major improvement in smooth pursuit gain could be attributed to drug treatment, based on a comparison of patient results before and after administration of levodopa.     

Hydergine treatment and psychophysiological measures in primary degenerative dementia

Changes in smooth pursuit eye movements and the P300 component of the auditory evoked potential were studied in patients with primary degenerative dementia during a double-blind, placebo-controlled study of ergoloid mesylates (Hydergine). After 18 weeks of treatment, P300 latency and amplitude, recorded at three scalp electrode sites, had not changed significantly. Smooth pursuit gain was elevated for the drug group under some stimulus conditions, suggesting a normalization of pursuit eye movement functioning. However, the results of several other measures of the quality of pursuit eye movements failed to corroborate this finding.     

The ocular motor defects in progressive supranuclear palsy

The results of quantitative infrared horizontal eye movement recordings in 8 patients with progressive supranuclear palsy are presented. Some of the patients had total paralysis of vertical movements, but none had completely lost the ability to perform horizontal eye movements. All patients had a defect in ocular fixation previously undescribed in this condition: the universal presence of square-wave jerks. Analysis of refixation sacades demonstrated hypometria, slow velocity/amplitude relationships, and profound prolongation of duration. The pursuit abnormality, characterized clinically by “cogwheel” eye movements, represented the inability to match eye velocity to target velocity. The ratio of peak eye velocity to peak target velocity (pursuit gain) was 0.2 to 0.5. Defects in the vestibuloocular reflex included inability to increase the gain of the reflex (ratio of peak eye velocity to head velocity) during viewing of a visible, stationary target and failure to suppress the reflex when viewing a target rotating with the head.     

Gaze-evoked nystagmus and smooth pursuit deficits: Their relationship studied in 52 patients

Gaze-evoked nystagmus occurs with cerebellar and brain-stem lesions and reflects a deficiency of the so-called common neural integrator. Experimental data show that loss of the neural integrator also abolishes slow conjugate eye movements, i.e. smooth pursuit eye movements and the vestibulo-ocular reflex (VOR). Since the smooth pursuit system has its own premotor circuits, a smooth pursuit deficit can be either the result of a premotor smooth pursuit lesion or the consequence of a gaze-holding deficit. To study this question DC eye movement recordings of 52 patients with horizontal gaze-evoked nystagmus and/or smooth pursuit deficits were studied in detail. It was found that the majority (71 %) had a combined smooth pursuit and gaze-holding deficit. Thirteen patients (25%) had a smooth pursuit deficit only. Only 2 patients (4%) had an isolated gaze-evoked nystagmus, which was comparatively weak. Thus a major finding is that each substantial gaze-evoked nystagmus is combined with a smooth pursuit deficit; the two deficits are well correlated (coefficientr =0.81). In all patients with a smooth pursuit deficit, visual suppression of the VOR was similarly impaired, when comparing the groups with and without gaze-evoked nystagmus. It is argued here that, although gaze-holding and smooth pursuit deficits are well correlated, the gaze-holding deficits seen in patients are not severe enough to explain the smooth pursuit deficit solely as a consequence of the gaze-holding deficit. Rather it probably reflects the close anatomical vicinity of gaze-holding and smooth pursuit mechanisms in the floccular region, the vestibular nuclei/nucleus prepositus complex and its connecting pathways.     

Eye movement deficits in schizophrenia

BACKGROUND: Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes in genetic studies of schizophrenia. The Icelandic population lends itself ideally to genetic studies due to its ethnic homogeneity and well-documented genealogy. The primary aim of this study was to assess AS and SPEM performance in a large Icelandic sample. Additional aims were to investigate the relationship between AS and SPEM task performance and to assess internal consistency, within-session performance changes and effects of SPEM target velocity on performance. METHOD: Patients with schizophrenia (N = 118) and healthy controls (N = 109) matched for age and gender underwent infrared oculographic assessment of AS and SPEM (at target velocities of 12 degrees , 24 degrees and 36 degrees /s). RESULTS: On the AS task patients displayed significantly more reflexive errors, longer latency, increased intra-individual latency variability, and reduced amplitude gain compared to controls. On the SPEM task, patients had significantly lower velocity gain and more frequent saccades during pursuit at all velocities, but group differences in velocity gain increased with increasing target velocity. Internal consistency of performance was high for all variables in both groups (Cronbach's alpha >0.77 for AS and >0.85 for SPEM) except for AS spatial error in patients (alpha = 0.38). A moderate association was found between AS and SPEM performance. By and large, patients and controls showed similar patterns of systematic within-session performance changes. CONCLUSIONS: Our findings confirm the existence of robust eye movement deficits in schizophrenia in a large sample. These measures may be studied as endophenotypes in future studies of potential schizophrenia risk genotypes in the genetically homogenous Icelandic population.     

Smooth-pursuit eye movements: alterations in Alzheimer's disease.

Smooth-pursuit eye movements induced by targets moving at constant velocities (from 5 to 100 deg/sec) were recorded from 13 patients with Alzheimer's disease (AD) and from 11 healthy subjects. Four variables were evaluated to quantify the patients' response to the eye movement tests: (1) average peak velocity of smooth-pursuit; (2) percent target matching index after saccade removal (percent ratio between the area of the velocity curve of smooth-pursuit eye movement after saccade removal and the area of target velocity) which is related to the eye performance for each value of target velocity; (3) total amplitude of anticipatory saccades; (4) total number of anticipatory saccades. Compared to the controls, AD patients were found to have significantly lower values of average peak velocity of smooth pursuit and of percent target matching index and a significantly increased number and amplitude of anticipatory saccades. A discriminant stepwise analysis indicated that 5 oculographic variables were significantly associated with the patient's clinical condition (healthy volunteer or AD patient). These statistics yielded an equation for predicting the patient's status according to which the percentage of cases classified correctly was 82.6% in the overall group (n = 23). The predictive performance was similar between the healthy volunteers subgroup (81.8%, n = 11) and the AD subgroup (83.3%, n = 12). The discriminant score was significantly correlated with the score resulting from the MiniMental test (r = 0.67). A significant correlation was also found between the MiniMental score and the number of anticipatory saccades (r = -0.61). No significant correlation was present between the gain of smooth pursuit and the patients' cognitive decline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ocular motor responses to unpredictable and predictable smooth pursuit stimuli among patients with obsessive-compulsive disorder.

This study was conducted to evaluate the smooth pursuit system functioning of patients with obsessive-compulsive disorder (OCD). For Study 1, 12 subjects with OCD and 12 nonpsychiatric subjects were administered 9-deg-per-sec ramp stimuli to elicit smooth pursuit eye movements. Consistent with a previous report, patients with OCD did not significantly differ from nonpsychiatric subjects on pursuit gain, or frequency of corrective and intrusive saccades. Patients with OCD, however, had smaller catch-up saccades during smooth pursuit than nonpsychiatric subjects. For Study 2, 12 subjects with OCD and 12 nonpsychiatric subjects were administered 2 different triangle wave stimuli with target velocities of 12 (0.2 Hz) deg per sec and 24 (0.4 Hz) deg per sec. Subjects with OCD and nonpsychiatric subjects did not significantly differ on any variable in the slow target velocity condition. When following 24-deg-per-sec targets, however, patients with OCD had significantly lower pursuit gain than the nonpsychiatric subjects. Results from Study 1 and 2 are consistent with the hypothesis that patients with OCD have a modest smooth pursuit deficit that is elicited only while following faster velocity targets.     

Correlation of Wisconsin Card Sorting Test performance with eye tracking in schizophrenia

The authors studied the relationship between performance on the Wisconsin Card Sorting Test and on the Trailmaking-B test and measures of smooth pursuit eye movements in 12 patients with chronic schizophrenia and 12 normal volunteers. They found that performance on the Wisconsin Card Sorting Test was significantly correlated with measures of smooth pursuit eye movements in schizophrenic patients but not in normal subjects. Trailmaking-B scores, however, were unrelated to smooth pursuit eye movements in either group.     

Failure of fixation suppression of caloric nystagmus and ocular motor abnormalities

Caloric nystagmus is substantially suppressed by visual fixation. The degree of suppression of caloric nystagmus is influenced by the condition of visual fixation. We studied the percent reduction in slow-phase velocity of caloric nystagmus by visual fixation and certain abnormalities in optokinetic nystagmus, smooth pursuit, and maintenance of ocular position of gaze in 38 patients with disorders of the CNS. The inability to suppress caloric nystagmus by visual fixation correlated with reduction in optokinetic nystagmus, deficit in smooth pursuit eye movements, and presence of gaze nystagmus. It seems probable that modulation of the vestibulo-ocular reflex is influenced by the same mechanisms that are concerned with optokinetic nystagmus, maintenance of ocular position of gaze, and smooth pursuit eye movements.     

Evidence from increased anticipation of predictive saccades for a dysfunction of fronto-striatal circuits in obsessive-compulsive disorder

In obsessive-compulsive disorder (OCD), a dysfunction of neuronal circuits involving prefrontal areas and the basal ganglia is discussed that implies specific oculomotor deficits. Performance during reflexive and predictive saccades, antisaccades and predictive smooth pursuit was compared between patients with OCD (n=22), patients with schizophrenia (n=21) and healthy subjects (n=24). Eye movements were recorded by infrared reflection oculography. In both patient groups, higher frequencies of anticipatory saccades with reduced amplitudes in the predictive saccade task were observed. Additionally, reduced smooth pursuit eye velocity and increased frequencies of saccadic intrusions during smooth pursuit as well as increased error rates in the antisaccade task were demonstrated for patients suffering from schizophrenia. Patients with OCD and schizophrenia revealed different patterns of oculomotor impairment: whereas increased anticipation of predictive saccades provides evidence for a dysfunction of the circuit between the frontal eye field and the basal ganglia in both groups, results from the antisaccade task imply additional deficits involving the dorsolateral prefrontal cortex in schizophrenic patients. Furthermore, the cortical network for smooth pursuit (especially the frontal eye field) is also assumed to be disturbed in schizophrenia.