Voluntary control of saccadic and smooth-pursuit eye movements in children with learning disorders

Eye movement is crucial to humans in allowing them to aim the foveae at objects of interest. We examined the voluntary control of saccadic and smooth-pursuit eye movements in 18 subjects with learning disorders (LDs) (aged 8–16) and 22 normal controls (aged 7–15). The subjects were assigned visually guided, memory-guided, and anti-saccade tasks, and smooth-pursuit eye movements (SPEM). Although, the LD subjects showed normal results in the visually guided saccade task, they showed more errors in the memory-guided saccade task (e.g. they were unable to stop themselves reflexively looking at the cue) and longer latencies, even when they performed correctly. They also showed longer latencies than the controls in the anti-saccade task. These results suggest that they find it difficult to voluntarily suppress reflexive saccades and initiate voluntary saccades when a target is invisible. In SPEM using step-ramp stimuli, the LD subjects showed lower open- and closed-loop gains. These results suggest disturbances of both acceleration of eye movement in the initial state and maintenance of velocity in minimizing retinal slip in the steady state. Recent anatomical studies in LD subjects have suggested abnormalities in the structure of certain brain areas such as the frontal cortex. Frontal eye movement-related areas such as the frontal eye fields and supplementary eye fields may be involved in these disturbances of voluntary control of eye movement in LDs.     

Target selection for pursuit and saccadic eye movements in humans

Eye movements were recorded from three subjects as they initiated tracking of a small circle ("target") moving leftward or rightward, above or below the horizontal meridian, either alone or in the presence of a small square ("distractor") moving leftward or rightward on the other side of the horizontal meridian. At the start of each trial, subjects were provided with either a "form" cue (always centrally positioned and having the circular shape and color of the upcoming moving target) or a "location" cue (a small white square positioned where the upcoming target would appear). The latency of pursuit increased in the presence of an oppositely moving distractor when subjects were provided the form cues but not when they were provided the location cues. The latency of saccades showed similar, but smaller, increases when subjects were given the form cues. On many trials with the form cues, pursuit started in the direction of the distractor and then reversed to follow the target. On these trials, the initial saccade often, but not always, also followed the distractor. These results indicate that the mechanisms of target selection for pursuit and saccades are tightly coordinated but not strictly yoked. The shared effects of the distractor on the latencies of pursuit and saccades probably reflect the common role of visual attention in filtering the inputs that guide these two types of eye movements. The differences in the details of the effects on pursuit and saccades suggest that the neural mechanisms that trigger these two movements can be independently regulated.     

Catecholamine depletion produces irrepressible saccadic eye movements in normal humans

To determine the effect of catecholamine depletion on ocular motor pathways in humans, we studied the eye movements of 3 normal subjects who received the drug metyrosine (alpha-methylparatyrosine). This drug temporarily depleted dopamine and norepinephrine, as measured by a reduction in the metabolite, 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG). Saccadic, pursuit, and vestibulo-ocular eye movements were recorded using infrared oculography with subjects both on placebo and on metyrosine. The most consistent effect observed with metyrosine was an increase in the amplitude and frequency of saccadic intrusions during fixation and pursuit. Two of the 3 subjects also had shortened time constants for the vestibulo-ocular reflex, attributable in part to the sedative effect of catecholamine depletion. The increase in saccadic intrusions implies that catecholamines modulate the activity of a subpopulation of suppressor motor neurons in the human brainstem.     

Effects of oxcarbazepine and carbamazepine on the central nervous system: computerised analysis of saccadic and smooth-pursuit eye movements

Oxcarbazepine (OXC) is a new anti-epileptic agent structurally related to carbamazepine (CBZ). OXC seems to have a similar efficacy and a better tolerability profile than CBZ. In the present study we compared the subclinical side-effects on the CNS of OXC and CBZ using a computerised analysis of saccadic and smooth-pursuit eye movements. Six healthy male volunteers (mean age 29 yrs) participated in the study, which was conducted by a double-blind cross-over design. Each subject was given a single dose of either CBZ 400 mg or OXC 600 mg (according to the random assignment) after which the drug effects on eye movements were evaluated. One week later, the trial was repeated using the other drug. The parametrisation of both saccadic and smooth-pursuit eye movements was carried out by measuring a series of performance parameters [e.g. the maximum saccade peak velocity (MSPV) and the typical target velocity (TTV)]. OXC was found to induce a lesser degree of alteration on the values of both MSPV (p = 0.07) and TTV (p less than 0.03) than CBZ. In particular, the TTV values were virtually unaffected by OXC administration, while the effects of CBZ on both variables were particularly evident at 8 and 10 h after dosing which correspond to the time at which the plasma concentrations of CBZ and of its 10,11-epoxide reach the peak. In conclusion, our preliminary results indicate that OXC induces negligible alterations, if any, on the eye movement parameters evaluated in our study.     

Cortical networks subserving pursuit and saccadic eye movements in humans: an FMRI study

High-field (3 Tesla) functional magnetic resonance imaging (MRI) was used to investigate the cortical circuitry subserving pursuit tracking in humans and compare it to that for saccadic eye movements. Pursuit performance, relative to visual fixation, elicited activation in three areas known to contribute to eye movements in humans and in nonhuman primates: the frontal eye field, supplementary eye field, and intraparietal sulcus. It also activated three medial regions not previously identified in human neuroimaging studies of pursuit: the precuneus and the anterior and posterior cingulate cortices. All six areas were also activated during saccades. The spatial extent of activation was similar for saccades and pursuit in all but two regions: spatial extent was greater for saccades in the superior branch of the frontal eye field and greater for pursuit in posterior cingulate cortex. This set of activations for smooth pursuit parallels the network of oculomotor areas characterized in nonhuman primates and complements recent studies showing that common cortical networks subserve oculomotor functions and spatial attention in humans.     

Multiple sclerosis: Cognition and saccadic eye movements

Ocular motor abnormalities are frequently reported in Multiple Sclerosis (MS), the most salient of which are well represented by the commonly used clinical measure, the EDSS. However, cognitive function, which is poorly represented by this scale, may also be ascertained from ocular motor measures, suggesting that an analysis of eye movements has the potential to extend and complement this more conventional measure. The generation of single and triple-step memory-guided saccades was investigated in 25 individuals with MS and a comparable number of neurologically healthy individuals matched for age and IQ. Experimental measures were correlated with a battery of neuropsychological tests evaluating attentional, working memory and executive processes, the cognitive domains most commonly compromised in MS. For single memory-guided saccades, MS patients were less accurate and generated more erroneous responses to non-target stimuli. Saccadic latencies were also prolonged. For triple-step memory-guided saccades, MS patients were less accurate and more variable. A number of significant correlations were revealed between measures of each of these characteristics and scores on the range of neuropsychological assessments. These ocular motor measures demonstrate considerable sensitivity with respect to evaluating cognitive function in MS, particularly working memory and inhibitory control processes. This suggests that they could represent the foundation of a user-friendly surrogate marker of disease severity and progression in MS.     

Early expression of a pathophysiological feature of schizophrenia: saccadic intrusions into smooth-pursuit eye movements in school-age children vulnerable to schizophrenia

OBJECTIVE: Neurodevelopmental hypotheses of schizophrenia propose that the responsible pathology occurs much earlier than the usual onset of illness in late adolescence. Nonspecific neurocognitive and behavioral deficits found in children vulnerable to schizophrenia support this hypothesis. This report describes early deficits in a putative genetic endophenotype, saccadic intrusions into smooth-pursuit eye movements (SPEM). METHOD: SPEM were recorded in 189 children aged 6-15 years: 49 children with schizophrenia, 60 nonpsychotic first-degree relatives, and 80 typically developing children. RESULTS: Children with schizophrenia demonstrated poorer gain and a significantly increased frequency of leading saccades and large anticipatory saccades; however, only leading saccades differentiated first-degree relatives from typical children. Admixture analysis indicates that 94% of children with schizophrenia, 50% of first-degree relatives, and 19% of typically developing children have abnormally increased frequencies of leading saccades. CONCLUSIONS: Typically developing young school-age children have a leading saccade phenotype similar to that of adults, suggesting this brain function is fully developed by early school-age years. The abnormal leading saccade phenotype, a schizophrenia-associated familial brain dysfunction, is present by 6 years of age, more than a decade before the highest risk for onset of psychosis. Treatment and prevention strategies will need to consider the early neurodevelopmental nature of schizophrenia.     

Saccadic and smooth-pursuit eye movements in deficit and non-deficit schizophrenia

We have analyzed eye movement performances in schizophrenics showing primary negative or deficit symptoms (n=16) and non-deficit schizophrenics (n=55), and compared them with those of controls (n=34) in order to study the relationships between negative symptoms and eye movement abnormalities. Patients were subtyped into deficit and non-deficit subgroups using the Schedule for the Deficit Syndrome. Three oculomotor paradigms were used: smooth pursuit, a reflexive saccade paradigm and an antisaccadic task.The smooth pursuit gain was significantly decreased (and the rate of catch-up saccades increased) in schizophrenics as compared with controls, but no difference was observed between patient groups. In the reflexive saccade paradigm, no difference was found between controls and patients, except for latency in deficit patients. In the antisaccade paradigm, the number of errors and the latency of successful antisaccades were significantly increased in schizophrenics as compared with controls. The latency of successful antisaccades in both directions was significantly increased in deficit patients as compared with non-deficit patients. The latency of rightward successful antisaccades was significantly increased as compared with the latency of leftward antisaccades in deficit patients only. However, when patients were classified into negative and non-negative groups using the PANSS, no difference was found in the antisaccade paradigm.Smooth pursuit impairment does not seem to depend on the primary enduring negative symptoms.In deficit schizophrenics, the abnormalities observed in the antisaccadic task are consistent with prefrontal dysfunction, and may suggest parietal lobe dysfunction as well.     

Slow saccadic eye movements in Wilson''s disease

This is the first reported case of Wilson's disease where a global defect of saccadic eye movements has been documented by electro-oculography. The defect of rapid eye movements is discussed in relation to current anatomical, pathological, and experimental work relating to the descending frontobulbar saccadic eye movement system. It is suggested that the caudate nucleus pathology in Wilson's disease might be responsible for the defect of saccadic movement by interrupting a descending polysynaptic pathway.     

Discharges of Purkinje cells in monkey's flocculus during smooth-pursuit eye movements and visual stimulus movements

Modulations in discharges of Purkinje cells (P cells) associated with movements of visual patterns were studied in the flocculus of monkeys trained to execute smooth-pursuit eye movements and to suppress optokinetic nystagmus. One class of P cells responded to the movements of visual stimulus regardless of whether the eyes remained stationary (produced retinal-slip velocity) or moved with the stimulus produced eye velocity). These P cells processed high-order information concerning the absolute velocity of stimulus movements and thereby the eye velocity had already been incorporated in the visual responses (visuomotor P cells). The other class of P cells responded to visual inputs resulting from the retinal slip (visual P cells). The majority of visual P cells (82%) also modulated their activities during smooth pursuit. When sinusoidal trackings were executed against a stationary visual background, various types of interactions occurred in the P-cell responses between the converging visual and oculomotor inputs. The type of interaction was related to the preferred direction for the P cell during eye movements and the side of the peripheral receptive field.     

Clinical examination of saccadic eye movements in hemianopia

We used two simple bedside tests of saccadic eye movements between two fingers as targets to study 23 hemianopic patients. With these tests, we could provide confirmation or, in malingering, exclusion of a hemianopia. Furthermore, the amount of ocular motor compensation for the loss of one half of the visual field could be estimated, and visual hemineglect was demonstrated. The findings in some cases with chronic homonymous hemianopia suggested "extrastriate vision."     

Applying a model of saccadic prediction to patients' saccadic eye movements

A mathematical model of eye tracking of periodic square wave target motion has previously been proposed. In this work the model was further studied with regard to saccadic response time to symmetrical square wave target motion in 6 patients with unilateral parietal lesions following cerebrovascular accidents. Three types of saccadic response time were noted. In patients with type I, saccades contralateral to the damaged hemisphere had similar characteristics to those found in ipsilateral direction, but with longer response time. In those with type II, the saccadic response time was about the same on movement in either direction for repetitive target cycle durations of 1.2 or 2.0 s. In patients with type III, the target motion could not be predicted, in either direction.     

Disturbed smooth pursuit and saccadic eye movements in schizophrenia

Smooth pursuit and saccadic eye movements of schizophrenic patients were examined. In a pendulum (0.5 Hz) tracking task schizophrenic inpatients had a slightly lower smooth pursuit gain than outpatients and controls, who showed no significant differences. The number of saccades, counter-saccades and velocity arrests occurring in a 20 s tracking epoque was the same in patients and controls, but patients made larger saccades. When tracking a stepping target by saccadic eye movements, schizophrenic inpatients, and to a lesser extent outpatients, exhibited longer reaction times than controls and had a higher incidence of "non-fixation" (saccades away from the target while the target is stationary). Schizophrenic patients also showed a significantly larger proportion of dysmetric saccades (undershooting the target). While similar changes of reaction time and non-fixation score were observed in manic-depressives and alcoholics, dysmetria was more often found in schizophrenics and possibly constitutes the expression of a specific impairment of attention.     

Cerebellar vermis involvement in monkey saccadic eye movements: Microstimulation

The cerebellar vermis (lobules V to VII) was focally stimulated (maximum current = 300 microA) through microelectrodes in alert monkeys trained to fixate on visual targets located at different positions in the eye movement field. Microstimulation of this area evoked saccades whose direction and amplitude were dependent on the spatial locus of the vermal point stimulated and on the position of the eye at the time of stimulation. Stimulation evoked saccades on most (70%) of the electrode penetrations. By alternatively stimulating and recording through the electrode as it advanced through the depth of the vermis, it was possible to map the threshold for evoking saccades along a penetration as well as to ascertain the type of tissue (white matter or Purkinje cell layer) situated at the stimulation points. On penetrations where saccades were evoked, there was generally one (90%) and sometimes two (10%) low-threshold region(s). These low-threshold regions were located in fiber tracks and not in the Purkinje or other cellular layers of the cerebellar cortex. The direction and size of the evoked saccades were dependent on position of the eye in the orbit. At a few sites, even the presence or the absence of an evoked saccade depended on the initial eye position. Postsaccadic drifts after termination of evoked saccades were also a common feature (50% of the tracks) associated with vermal microstimulation. The presence or absence as well as the direction of the postsaccadic drift were also dependent on initial eye position. These observations suggest that the vermal stimulations evoked saccades by the antidromic activation of mossy fiber afferent inputs that emanate from the brain stem saccadic burst generator. Furthermore, stimulation in this manner would actually bypass the cerebellar circuitry and produce saccades without the usual modifying influence of the cerebellum.     

Quantitative assessment of smooth-pursuit eye movements in healthy and epileptic subjects.

A quantitative electro-oculographic method was used to assess the impairment in smooth-pursuit and vestibulo-ocular reflex suppression eye movements in 12 epileptic patients and eight normal volunteers. Both types of eye movement were impaired by a factor of 40% in the epileptic patients, and the impairment was at least partly due to the treatment with phenytoin and phenobarbitone. There was a strong positive correlation between the performances in vestibulo-ocular reflex suppression and smooth-pursuit.     

Age-dependent changes in visually guided saccadic eye movements

Voluntary horizontal saccadic eye movements (SEM) were recorded in 148 drug free healthy subjects (15-75 years of age). None had history and/or objective evidences of CNS abnormalities. SEM recordings took place always at the same time of the day, after a standard lunch. Peak saccadic velocity (PSV), saccade latency (SL) and saccade accuracy (SA) were extracted for each saccade session. A negative linear correlation was found between SEM parameters (PSV, SA, SL) and age. Aged subjects showed a significant (p less than 0.01) elongation of the to locate the target, a significant (p less than 0.01) decrease in PSV and a significant (p less than 0.01) decrement in SA.     

Disturbed smooth pursuit and saccadic eye movements in schizophrenia

Summary Smooth pursuit and saccadic eye movements of schizophrenic patients were examined. In a pendulum (0.5 Hz) tracking task schizophrenic inpatients had a slightly lower smooth pursuit gain than outpatients and controls, who showed no significant differences. The number of saccades, counter-saccades and velocity arrests occuring in a 20 s tracking epoque was the same in patients and controls, but patients made larger saccades. When tracking a stepping target by saccadic eye movements, schizophrenic inpatients, and to a lesser extent outpatients, exhibited longer reaction times than controls and had a higher incidence of non-fixation (saccades away from the target while the target is stationary). Schizophrenic patients also showed a significantly larger proportion of dysmetric saccades (undershooting the target). While similar changes of reaction time and non-fixation score were observed in manic-depressives and alcoholics, dysmetria was more often found in schizophrenics and possibly constitutes the expression of a specific impairment of attention.     

Evoked potential augmenting-reducing in psychopaths and criminals with impaired smooth-pursuit eye movements

Previous studies that have assessed a stimulation-seeking theory of psychopathy are open to the criticism that psychopaths may lie on self-report questionnaires. The present study uses event-related potential (ERP) augmenting-reducing as a psychophysiological analog of stimulation-seeking in psychopaths to test this theory. It is also hypothesized that "schizoid" criminals, as defined by poor eye tracking, would show nonaugmenting/reducing, a profile characteristic of schizophrenia. Schizoid criminals were found to be characterized by nonaugmenting/reducing, but psychopaths were not found to be characterized by augmenting. It is concluded that stimulation-seeking is a viable theory of criminality but not of psychopathy, and that the etiological basis to schizoid criminality may differ substantially from criminality, per se.