Impaired Smooth Pursuit Eye Movements Research Articles

Istradefylline Improves Impaired Smooth Pursuit Eye Movements in Parkinson's Disease.

Patients with Parkinson's disease (PD) exhibit alterations in eye movement control, primarily diverse oculomotor deficits which include hypometric saccade and impaired smooth pursuit with reduced pursuit-gain necessitating catch-up saccades. The effects of dopaminergic treatment of PD on eye movements are controversial. Previous studies suggest that smooth pursuit eye movements (SPEMs) are not directly influenced by the dopaminergic system. The nondopaminergic drug istradefylline, a selective adenosine A2A receptor antagonist, reduces the OFF time and improves somatomotor function in levodopa-treated PD. Here, we investigated whether istradefylline improves SPEMs in PD, and determined whether oculomotor performance is associated with somatomotor performance. Using an infrared video eye tracking system, we quantified horizontal SPEMs in six patients with PD before and 4-8weeks after initiation of istradefylline administration. A further five patients with PD were tested before and after a 4-week interval without istradefylline to control for practice effects. We evaluated smooth pursuit gain (eye velocity/target velocity), accuracy of smooth pursuit velocity, and saccade rate during pursuitbefore and after istradefylline administration during the ON state. Patients received istradefylline by single daily oral administration at 20 to 40mg. Eye tracking data were obtained 4-8weeks after initiation of istradefylline administration. Istradefylline increased smooth pursuit gain and the accuracy of smooth pursuit velocity, and tended to decrease saccade rates during pursuit. Istradefylline ameliorated the oculomotor deficit in SPEM of patients with PD, although differences in somatomotor performance before and after istradefylline treatment were not significant during ON periods. The discrepancy observed between the oculomotor and somatomotor responses to istradefylline supports previous findings that SPEM is at least partially under nondopaminergic control.

Long-Term Effects of Low-Level Blast Exposure and High-Caliber Weapons Use in Military Special Operators.

Chronic low-level blast exposure has been linked with neurological alterations and traumatic brain injury (TBI) biomarkers. Impaired smooth-pursuit eye movements (SPEM) are often associated with TBI. The purpose of this study was to determine whether long-term operators of low-level blast exposure or high-caliber weapons use displayed oculomotor behaviors that differed from controls. Twenty-six members of an elite military unit performed a computerized oculomotor testing task using an eye tracker and completed a concussion assessment questionnaire. The participants were split into a blast exposure group and control group. The blast exposure group had a history of exposure to low-level blasts or high-caliber weapon use. The results revealed significant differences in SPEM, saccades, and fixations between the blast exposure group and control group. The blast exposure group’s eye movements were slower, stopped at more frequent points when following a target, traveled further from the target in terms of both speed and direction, and showed higher rates of variation and inefficiency. Poor oculomotor behavior correlated with a higher symptom severity on the concussion assessment questionnaire. Military special operators exposed to long-term low-level blasts or high-caliber weapons usage displayed an impaired oculomotor behavior in comparison to controls. These findings further our understanding of the impact of long-term low-level blast exposure on the oculomotor behavior of military special operators and may inform practical implications for military training.

Retinal and optic nerve degeneration in \u03b1-mannosidosis

Backgroundα-mannosidosis is a rare, autosomal-recessive, lysosomal storage disease caused by a deficient activity of α-mannosidase. Typical symptoms include intellectual, motor and hearing impairment, facial coarsening, and musculoskeletal abnormalities. Ocular pathologies reported previously were mainly opacities of the cornea and lens, strabismus, and ocular motility disorders. However, retinal and optic nerve degeneration have been rarely described.MethodsWe report ocular findings of 32 patients with α-mannosidosis. We particularly concentrated on retinal abnormalities which we supported by posterior segment examination, fundus photography, and Spectral-Domain optical coherence tomography (SD-OCT) imaging.ResultsTapeto-retinal degeneration with bone spicule formations in the peripheral retina or macular changes were seen in three patients (9.4%) on funduscopy; of these, two with optic nerve atrophy. Eight retinal images could be obtained by OCT or fundus photography; of these, six showed thinning of the outer retinal layers on OCT. Overall, optic nerve atrophy was seen in six patients (18.8%); of these, four with partial atrophy. Two patients had partial optic nerve atrophy with no retinal abnormalities on funduscopy. Cataract was seen in two (6.3%), corneal haze also in two patients (6.3%). Six patients (18.8%) had manifest strabismus, four (12.5%) nystagmus, and in five patients (15.6%) impaired smooth pursuit eye movements were seen.ConclusionOcular pathologies are not exclusively confined to opacities of the cornea and lens or strabismus and ocular motility disorders but tapeto-retinal degeneration and optic nerve atrophy may be a common feature in α-mannosidosis. OCT technology helps detecting early outer retinal thinning which can progress with age and potentially leads to vision loss over time.

Schizotypy and smooth pursuit eye movements as potential endophenotypes of obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.

Combining two model systems of psychosis: The effects of schizotypy and sleep deprivation on oculomotor control and psychotomimetic states.

Model systems of psychosis, such as schizotypy or sleep deprivation, are valuable in informing our understanding of the etiology of the disorder and aiding the development of new treatments. Schizophrenia patients, high schizotypes, and sleep-deprived subjects are known to share deficits in oculomotor biomarkers. Here, we aimed to further validate the schizotypy and sleep deprivation models and investigated, for the first time, their interactive effects on smooth pursuit eye movements (SPEM), prosaccades, antisaccades, predictive saccades, and measures of psychotomimetic states, anxiety, depression, and stress. To do so, n = 19 controls and n = 17 high positive schizotypes were examined after both a normal sleep night and 24 h of sleep deprivation. Schizotypes displayed higher SPEM global position error, catch-up saccade amplitude, and increased psychotomimetic states. Sleep deprivation impaired SPEM, prosaccade, antisaccade, and predictive saccade performance and increased levels of psychotomimetic experiences. Additionally, sleep deprivation reduced SPEM gain in schizotypes but not controls. We conclude that oculomotor impairments are observed in relation to schizotypy and following sleep deprivation, supporting their utility as biomarkers in model systems of psychosis. The combination of these models with oculomotor biomarkers may be particularly fruitful in assisting the development of new antipsychotic or pro-cognitive drugs.

Optokinetic nystagmus reflects perceptual directions in the onset binocular rivalry in Parkinson's disease.

Optokinetic nystagmus (OKN), the reflexive eye movements evoked by a moving field, has recently gained interest among researchers as a useful tool to assess conscious perception. When conscious perception and stimulus are dissociated, such as in binocular rivalry—when dissimilar images are simultaneously presented to each eye and perception alternates between the two images over time—OKN correlates with perception rather than with the physical direction of the moving field. While this relationship is well established in healthy subjects, it is yet unclear whether it also generalizes to clinical populations, for example, patients with Parkinson’s disease. Parkinson’s disease is a motor disorder, causing tremor, slow movements and rigidity. It may also be associated with oculomotor deficits, such as impaired saccades and smooth pursuit eye movements. Here, we employed short-duration, onset binocular rivalry (2 s trial of stimulus presentation followed by 1 s inter-trial interval) with moving grating stimuli to assess OKN in Parkinson’s disease patients (N = 39) and controls (N = 29) of a similar age. Each trial was either non-rivalrous (same stimuli presented to both eyes) or rivalrous, as in binocular rivalry. We analyzed OKN to discriminate direction of stimulus and perception on a trial-by-trial basis. Although the speed of slow-phase OKN was slower in the patients, discriminability of conscious perception based on OKN was comparable between the groups. Treatment with anti-Parkinson drugs and deep brain stimulation improved motor ability of patients, but did not impact on OKN. Furthermore, OKN-based measures were robust and their latencies were shorter than manual button-based measures in both groups and stimulus conditions. To our knowledge, our study is the first to demonstrate that OKN can be used as a reliable indicator of conscious perception in binocular rivalry even in Parkinson’s disease patients in whom impaired manual dexterity may render button-press reports less reliable.

Postural Ataxia in Cerebellar Downbeat Nystagmus: Its Relation to Visual, Proprioceptive and Vestibular Signals and Cerebellar Atrophy.

BackgroundThe cerebellum integrates proprioceptive, vestibular and visual signals for postural control. Cerebellar patients with downbeat nystagmus (DBN) complain of unsteadiness of stance and gait as well as blurred vision and oscillopsia.ObjectivesThe aim of this study was to elucidate the differential role of visual input, gaze eccentricity, vestibular and proprioceptive input on the postural stability in a large cohort of cerebellar patients with DBN, in comparison to healthy age-matched control subjects.MethodsOculomotor (nystagmus, smooth pursuit eye movements) and postural (postural sway speed) parameters were recorded and related to each other and volumetric changes of the cerebellum (voxel-based morphometry, SPM).ResultsTwenty-seven patients showed larger postural instability in all experimental conditions. Postural sway increased with nystagmus in the eyes closed condition but not with the eyes open. Romberg’s ratio remained stable and was not different from healthy controls. Postural sway did not change with gaze position or graviceptive input. It increased with attenuated proprioceptive input and on tandem stance in both groups but Romberg’s ratio also did not differ. Cerebellar atrophy (vermal lobule VI, VIII) correlated with the severity of impaired smooth pursuit eye movements of DBN patients.ConclusionsPostural ataxia of cerebellar patients with DBN cannot be explained by impaired visual feedback. Despite oscillopsia visual feedback control on cerebellar postural control seems to be preserved as postural sway was strongest on visual deprivation. The increase in postural ataxia is neither related to modulations of single components characterizing nystagmus nor to deprivation of single sensory (visual, proprioceptive) inputs usually stabilizing stance. Re-weighting of multisensory signals and/or inappropriate cerebellar motor commands might account for this postural ataxia.

Impairment of smooth pursuit eye movements in patients with multiple system atrophy and idiopathic Parkinson's disease

Objectives: It is well known that patients with multiple system atrophy of cerebellar type (MSA-C) show impaired smooth pursuit eye movements (SPEM) due to their cerebellar pathology. To what extent SPEM are also affected in other MSA subtypes or in idiopathic Parkinson's disease (IPD) is less clear. In this study, we investigated if quantitative measurements of SPEM may help to discriminate between subtypes of MSA as well as between MSA and IPD.

Eye movements and psychiatric disease.

During the past year a number of studies have been published on eye movement dysfunction in patients with psychiatric disease. According to the mainstream of modern neuropsychiatric research, these studies cover either genetic aspects or the results of pharmacological manipulation. A few studies addressed impaired smooth pursuit eye movements (eye tracking dysfunction) in unaffected relatives of psychiatric patients, and were important in excluding non-specific effects (e.g. medication) and isolating genetic predisposition to the disease. This predisposition could be demonstrated in families of schizophrenic patients irrespective of whether the index case was sporadic or familial. One large study demonstrated pathological distributions of various parameters of smooth pursuit eye movement performance in groups of schizophrenic patients and their relatives. However, another study challenged the specificity of eye tracking dysfunction as a trait marker for schizophrenia by showing that its prevalence was identical among relatives of patients with affective disorder and schizophrenia. Eye tracking dysfunction was associated with two gene polymorphisms that interfere with dopamine metabolism and are thus reasonable candidate genes for the predisposition to schizophrenia. The influence of nicotine and neuroleptic drugs on eye movement performance was studied in schizophrenic patients. Nicotine improved smooth pursuit performance in three studies, one of which attributed this finding to enhanced attention. Two groups of schizophrenic patients treated with two different atypical neuroleptic drugs, risperidone and olanzapine, did not differ in a battery of saccadic tasks. Eye movements provide an important tool to measure pharmacological effects in patients and unravel genetic traits in psychiatric disease.

視標追跡眼運動と半規管眼運動の相互作用について

Impaired smooth pursuit eye movements may be corrected by saccades to repair visual errors during an eye tracking test (ETT).However, in this study, most of the cases that showed a saccadic pattern during ETT demonstrated smooth eye movements in a pendular rotation test (PRT) with the eyes open and fixed at the stand still target in lightness due to interaction between the visuoocular and vestibuloocular systems. The incidence and character of the two kinds of induced eye movements in horizontal ETT and PRT with the eyes open were investigated.Investigated were thirty one cases among out-patients in the Neuro-Otological Clinic of Kitasato University Hospital in 1996. All cases showed saccadic patterns in ETT, fulfilling the following criteria: each half period to the right and left containing three or more saccades with a maximum amplitude of four or more degrees. Only 3 cases or 10% of the 31 patients showed saccadic pattern in PRT with the eyes open.The saccadic index (S.I.) (maximum amplitude multiplied by the number of saccades) was calculated in each case. The combined SI of both directions was between 75.8 to 100.6 in the 3 cases who had saccadic pattern in PRT with the eyes open. VOR gains remained in the low range (0.40 to 0.57). However, cases who showed high S.I. in ETT, but had smooth pursuit eye movement in PRT with the eyes open showed a high VOR gain. We concluded that most cases of saccadic pattern in ETT showed smooth eye movements in PRT with the eyes open and fixed at the target due to a high VOR gain, but in 10% of cases no increase was recorded due to a failure of vestibular compensation.

Dependence of impaired eye tracking on deficient velocity discrimination in schizophrenia.

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. 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. 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. 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.

Acquired Supranuclear Ocular Motor Paresis Following Cardiovascular Surgery

Acquired supranuclear ocular motor paresis is a rare disorder characterized by impaired saccadic and smooth pursuit eye movements in one or more directions of gaze. Vestibularly induced eye movements, however, are preserved. Six adult patients developed an acquired supranuclear ocular motor paresis following cardiopulmonary bypass surgery. Neuroimaging studies were normal in two patients and were consistent with small vessel ischemia in four patients. The mean cardiopulmonary bypass time was 132.3 min, and mean circulatory arrest time was 38.7 min; these were not outside established norms for this type of surgery. Patients undergoing cardiopulmonary bypass procedures with deep hypothermia are at risk for acquired supranuclear ocular motor paresis, but the development of this syndrome may not be predictable by duration of circulatory arrest or cardiopulmonary bypass times.

Smooth pursuit eye movements and neuropsychological impairments in schizophrenia.

Smooth pursuit eye movements (SPEM) and neuropsychological performance were examined in a sample of 29 drug-treated schizophrenic patients and 22 healthy controls. Patients had impairment in SPEM as well as in a wide range of neuropsychological tests (Wechsler Adult Intelligence Scale, Wisconsin Card Sorting Test. Finger Tapping, Reaction time, Selective attention, Trail-Making and Simultaneous Capacity). Performance indices were more affected than strategy-executive indices. Drug type (clozapine vs typical) and dose (chlorpromazine units) were not related to neuropsychological impairment among the patients. Indices from the whole range of tests accurately predicted a subjects' group identity (patient vs control). Impaired SPEM was predicted more accurately by tests assessing frontal functions. Seven patients, all men, had only marginal neuropsychological impairments.

The effects of remoxipride and chlorpromazine on eye movements and psychomotor performance in healthy volunteers

Fifteen healthy male volunteers received single doses of 100 mg immediate release remoxipride (IR), 150 mg controlled release remoxipride (CR), 50 mg chlorpromazine (CPZ), 2 mg lorazepam (LZ), and placebo in a randomised, five-period cross-over study. Both saccadic (SEM) and smooth pursuit eye movements (SPEM) as well as a battery of psychomotor performance tests were assessed at 1.5-h intervals over 9 h following drug administration. The areas under the response-time curves and the maximum effect during the study period were analysed by analysis of variance. The most consistent impairments were produced by LZ. The neuroleptics caused impairments to SEM, and tended to impair critical flicker fusion, continuous attention and both paced and unpaced versions of the digit-symbol substitution test as well as subjective measures of sedation. Only LZ impaired SPEM. Neither paced nor unpaced psychomotor tests distinguished between neuroleptics and benzodiazepines. The low therapeutic doses of IR and CR produced similar impairments to a sub-therapeutic dose of CPZ. Selectivity of pharmacological action does not appear to predict selectivity of effect on psychomotor function.

Evidence of impaired smooth pursuit eye movement performance in crack cocaine users

A recent single photon emission computed tomography (SPECT) brain imaging study of heavy cocaine abusers in their second week of abstinence reported a high frequency of focal perfusion abnormalities involving inferoparietal, temporal, and anterofrontal cortices and basal ganglia (Holman et al 1991). As the brain areas with perfusion detects described in this SPECT study are regarded as important in mediating various voluntary eye movements (Leichnetz and Goldberg 1988), the fbllowing study was carried out to compare the smooth pursuit eye movement (SPEM) performance of cocaine-dependent individuals to the SPEM performance of patients with schizophrenia as well as a population of normal subjects. Measurable SPEM disturbance is quite common in schizophrenia (Clementz and Sweeney 1990).

垂直性振子様眼球運動を呈した椎骨脳底動脈瘤の一症例

Acquired pendular continuous eye movement was observed in a 43-year-old male with vertebral basilar aneurysm. He complained of gait disturbance, numbness on extremities and vertical oscillopsia. Vertical pendular eye movements with frqeuencies ranging from 3to 4 Hz and amplitudes between 5 and 15 degrees with eye's open in the dark were recorded. This patient demonstrated impaired smooth pursuit eye movement and optokinetic nystagmus in the horizontal and vertical axis.The saccade velocity was reduced markedly.The vertebral-basilar aneurysm of 12 mm in a diameter was confirmed by CT and VAG at the level of the pons.Eight years after the onset of the initial symptoms, adduction disturbance in both eyes were developed and bilateral MLF syndrome revealed. At the time, vertical pendular eye movements were completely disappeared. From the findings of neurotological examinations, mechanism of vertical pendular eye movement was discussed.

Stimulus characteristics influence the gain of smooth pursuit eye movements in normal subjects

Impaired smooth pursuit eye movements are commonly believed to indicate a lesion of the central nervous system. Smooth pursuit performance, however, is strongly dependent on non-specific variables like cooperation, arousal and attentiveness. Therefore, disturbed smooth pursuit can be attributed either to lesions of the smooth pursuit system per se, or to the influence of non-controlled variables (non-structural disturbances). This renders the evaluation of smooth pursuit uncertain. In the present study we attempted to design a stimulus that yields smooth pursuit eye movements, which are not influenced by uncontrolled variations of state and input, for a better separation of structural lesions of the pursuit system and the effect of nonspecific variables. Our results suggest that a stimulus that leads to a centrally generated representation (percept) of motion is most suitable to elicit high gains of smooth pursuit (sigma pursuit), but only if attentiveness is optimal. Beta-motion (motion elicited by discrete steps of the target) or real target motion are capable to render the smooth pursuit performance optimal, even with low attentiveness, when the fixation point and its wider surroundings or enough discrete points in the neighbourhood move in the same direction in space.

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.

Clinical, psychophysiological, and neurological characteristics of volunteers with impaired smooth pursuit eye movements

Two hundred eighty-five volunteers from a community college were screened on campus for accuracy of their smooth pursuit eye movements (SPEM) by electrooculograph (EOG). Those volunteers with the least and the most accurate SPEM were recalled to the laboratory for a comprehensive evaluation of clinical and demographic characteristics, family history, neurological status, and psychophysiological and biological measures, including SPEM [repeat EOG test and infrared (IR) test], an electroencephalogram, auditory and visual evoked potentials, reaction time (RT), the continuous performance task (CPT), platelet monoamine oxidase (MAO), plasma amine oxidase, and dopamine-beta-hydroxylase (DBH). Low-accuracy SPEM was associated with social isolation, inadequate rapport, eccentricity, and a variety of related schizotypal or schizophrenia-like characteristics, but not with generalizedpsychopathology or other demographic/medical/ clinical history variables. Low-accuracy SPEM also was associated with neurological and psychophysiological abnormalities frequently observed in schizophrenic patients. These results suggest that impaired SPEM may reflect an underlying central nervous system dysfunction that is specifically associated with clinical and biological characteristics related to schizophrenia, even in the absence of overt schizophrenia.

Smooth pursuit eye movements in dementia of the Alzheimer type.

Smooth pursuit eye movements (SPEM) to a sinusoidally modulated target moving horizontally across a cathode ray tube screen were examined for 17 patients with dementia of the Alzheimer type (DAT) and for 14 age-matched control subjects. There were 3 target-motion conditions at frequencies representing varying ranges of target velocity. DAT patients differed from controls on all measures of smooth pursuit quality: their gain was reduced at high target velocities and lower target accelerations, they made more frequent directionally appropriate saccades and had more saccadic intrusions, they led the target with their eyes (phase lead) in all 3 conditions, and lag-adjusted cross-correlation coefficients, computed between digitized eye-movement and target signals, were lower among patients. The cross-correlation measure was most sensitive to between-group variability. These results suggest that the impaired SPEM observed in DAT patients reflect degeneration of cortical oculomotor centers, either through inappropriate saccadic intrusions in smooth pursuit as a result of physiologic disinhibition or through effects on attentional processes or both.