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[Eye movement abnormalities as a sign for the diagnosis in Niemann-Pick disease type C].

BACKGROUND: Eye movement abnormalities in familial mental retardation syndrome should lead to the suspicion of a storage disorder, including Niemann Pick disease type C, Gaucher's disease, abetalipoproteinemia and Wilson's disease. The eye movement abnormalities in our two patients were suggestive of Niemann Pick disease type C, characterized by initial loss of voluntary vertical eye movements and subsequent loss of horizontal eye movements, with preservation of the vestibulo-ocular response. The characteristics of eye movements in storage disorders are different. In Gaucher's disease a progressive horizontal gaze palsy, in abetalipoproteinemia a particular type of internuclear ophthalmoplegia with nystagmus of the adducting eye and in Wilson's disease slowing of saccades may be observed. PATIENTS: We evaluated two mentally retarded sisters with unclear diagnosis at the age of 34 and 27 years. At the age of 24 and 21 a vertical gaze palsy led to the diagnosis of Parinaud syndrome. RESULTS: At the time of our examination both sisters were unable to perform voluntary horizontal or vertical saccades or pursuit eye movements. The vestibulo-ocular reflex was present in all directions. Optokinetic nystagmus and convergence were absent. This clinical picture led us to a suspicion of Niemann-Pick disease type C, confirmed by the presence of sea-blue histiocytes in the bone marrow biopsy. CONCLUSION: These cases demonstrate that the pattern of eye movement disorders in some syndromes associated with mental retardation can give important clues in the determination of the diagnosis.

Adult↗

MR-eyetracker: a new method for eye movement recording in functional magnetic resonance imaging.

We present a method for recording saccadic and pursuit eye movements in the magnetic resonance tomograph designed for visual functional magnetic resonance imaging (fMRI) experiments. To reliably classify brain areas as pursuit or saccade related it is important to carefully measure the actual eye movements. For this purpose, infrared light, created outside the scanner by light-emitting diodes (LEDs), is guided via optic fibers into the head coil and onto the eye of the subject. Two additional fiber optical cables pick up the light reflected by the iris. The illuminating and detecting cables are mounted in a plastic eyepiece that is manually lowered to the level of the eye. By means of differential amplification, we obtain a signal that covaries with the horizontal position of the eye. Calibration of eye position within the scanner yields an estimate of eye position with a resolution of 0.2 degrees at a sampling rate of 1000 Hz. Experiments are presented that employ echoplanar imaging with 12 image planes through visual, parietal and frontal cortex while subjects performed saccadic and pursuit eye movements. The distribution of BOLD (blood oxygen level dependent) responses is shown to depend on the type of eye movement performed. Our method yields high temporal and spatial resolution of the horizontal component of eye movements during fMRI scanning. Since the signal is purely optical, there is no interaction between the eye movement signals and the echoplanar images. This reasonably priced eye tracker can be used to control eye position and monitor eye movements during fMRI.

Brain↗

Target anticipation and impairment of smooth pursuit eye movements in schizophrenia.

A reduced gain of smooth pursuit eye velocity has frequently been reported in schizophrenic patients. With respect to predictable stimuli, this could be due to a deficit in predicting the target path. To determine this contribution to smooth pursuit eye movement performance, we analyzed the ocular smooth pursuit response to a sinusoidally moving target that was suddenly stopped after some cycles of regular movement. Horizontal eye movements were recorded with infrared reflection oculography in a group of 17 schizophrenic in-patients and 16 age-matched healthy subjects for controls. The patients exhibited a reduced gain of smooth pursuit velocity, but phase lag was not different from the control group. After the unpredictable stop of target movement, predictive sinusoidal smooth pursuit was maintained for 150 to 200 ms in both groups. The resulting maximal position and velocity error was larger in the patient group. In conclusion, schizophrenic patients were able to generate a normal anticipatory component of smooth pursuit and to switch it off in response to external demands. They showed, however, an increased velocity of anticipatory pursuit, which might be used to compensate for the primary deficit of smooth pursuit velocity frequently found in schizophrenics.

Adaptation, Physiological↗

3-D eye movement analysis.

This paper presents a novel three-dimensional (3-D) eye movement analysis algorithm for binocular eye tracking within virtual reality (VR). The user's gaze direction, head position, and orientation are tracked in order to allow recording of the user's fixations within the environment. Although the linear signal analysis approach is itself not new, its application to eye movement analysis in three dimensions advances traditional two-dimensional approaches, since it takes into account the six degrees of freedom of head movements and is resolution independent. Results indicate that the 3-D eye movement analysis algorithm can successfully be used for analysis of visual process measures in VR. Process measures not only can corroborate performance measures, but also can lead to discoveries of the reasons for performance improvements. In particular, analysis of users' eye movements in VR can potentially lead to further insights into the underlying cognitive processes of VR subjects.

Adult↗

Gain adaptation and phase dynamics of compensatory eye movements in mice.

The vestibulocerebellum is involved in the control of compensatory eye movements. To investigate its role in the learning and timing of motor behaviour, eye movements in normal and mutant mice were investigated for the first time with the use of search coils. Wild-type mice showed the ability to increase the gain of their vestibulo-ocular reflex by visuo-vestibular training. This adaptation did not occur in lurcher mice, a natural mouse mutant that completely lacks Purkinje cells. During the optokinetic reflex the phase (timing) of the eye movements of lurchers lagged behind that of wild-type littermates, whereas during the vestibulo-ocular reflex it led that of the wild types. Ablations of different parts of the vestibulocerebellum indicated that the flocculus is necessary for the adaptation and the phase-leading effects of the cerebellum, whereas the nodulus might contribute to its phase-lagging effects. We conclude that Purkinje cells in the vestibulocerebellum are necessary for both learning and timing of compensatory eye movements in mice, and that the flocculus and nodulus may play antagonistic roles in these processes. The present description of the basic principles of cerebellar eye-movement control opens up the possibility to investigate the mechanisms of this motor behaviour at the molecular level in genetically manipulated mutant mice.

Adaptation, Physiological↗

Effect of intravenous diazepam and thiopental on voluntary saccades and pursuit eye movements.

The effects of diazepam and thiopental on voluntary saccades and pursuit eye movements were tested in 9 volunteers, with an interval of at least 2 weeks between tests. One, 4 and 8 h after intravenous injection of diazepam (0.3 mg/kg) or thiopental (6.0 mg/kg), voluntary saccades and pursuit eye movements were tested and blood samples taken for analysis of drug concentration. As compared to results of tests without drugs, a significant reduction both of saccadic peak velocity and gain of pursuit eye movements was found 1 h after injection of either drug, but not after 4 and 8 h. The amplitude of saccades elicited with the 60 degrees stimulus was significantly reduced 1 h after injection of diazepam. Latency of saccades increased significantly up to 4 h after injection of either drug. No significant correlation was found between peak velocity of saccades and blood concentration of either thiopental or diazepam 1 h after administration. The present results confirm that in man saccades and pursuit eye movements are reduced by benzodiazepines and barbiturates, but provide no support for the previously described efficacy of saccades in monitoring the effect of benzodiazepines. It is hypothesized that diazepam and thiopental also induce reduction of voluntary saccades and pursuit eye movements via a general sedation of the central nervous system (CNS), besides having specific effects on CNS structures important to the performance of voluntary eye movements.

Adult↗

Effects of eye movements upon excitability of the superior colliculus in cats.

Influences of saccadic eye movements upon excitability of cat superior colliculus (SC) were examined in chronic cats carrying implanted electrodes and in encephale isole cats. Excitability of SC was assessed by recording orthodromic responses of SC (SC ortho-response) to electrical stimulation of the optic chiasm. The SC ortho-response consisted of four components; i.e. presynaptic T1 and postsynaptic C1, C2 and C3. Eye movements suppressed the first two components (T1 and C1) and enhanced the latter two (C2 and C3). Retinal impulses caused by movements of images were found responsible for suppression of T1 and C1: 1) This was seen when cats moved eyes seeing external objects in light. In dark, neither T1 nor C1 received any influence from eye movements. 2) By moving visual stimuli rapidly before eyes of paralysed cats the same suppression of T1 and C1 was obtained. Suppression of C1 was deemed as a postsynaptic sign of SC for saccadic suppression. In contrast to suppression of T1 and C1, enhancement of C2 and C3 was dependent upon a central factor: 1) Enhancement of C2 and C3 followed eye movements, independent of the ambient illumination. 2) Saccade-like movements of a slit of light in front of immobilized eyes never induced enhancement of C2 and C3. 3) PRF stimulation, effective to cause saccade-like eye movements, always elicited enhancement of C2 and C3, independent of the ambient condition and even after eyes had been immobilized. This phenomenon was interpreted as indicating that corollary discharges are sent to SC.

Animals↗

[Diagnosis of myasthenic eye signs. Clinical signs and electronystagmographical findings of saccadic eye movements (author's transl)].

The clinical eye signs of 31 myasthenic patients are presented and those signs important for an early diagnosis are then discussed: lid symptoms caused by fatigue (Simpson-test), characteristic lid twitches as well as alternating asymmetrical eye muscle pareses. The importance of an investigation with the tangent scale in the course of which tensilon is injected is pointed out. False diagnosis and differential diagnostic signs are then considered (disseminated sclerosis, aneeurysm, encephalitis, pseudopulbarparalysis). - Our electronystagmographical investigations of saccadic eye movements showed hypometric, alternating saccades with occasional nystagmuslike jerks. After Tensilon injection hypermetric saccades (overshoots) were observed which depended on a disproportion of the supranuclear oculomotor centers and the eye muscles. The "muscleparetic" nystagmus is a pathologically increased endposition nystagmus. The hypometric nystagmuslike jerks during a saccadic eye movement are caused by insufficient phasic innervation.

Adolescent↗

Rapid eye movement density shows trends across REM periods but is uncorrelated with NREM delta in young and elderly human subjects.

Saccade-like eye movements are the most prominent phasic component of rapid eye movement (REM) sleep. Eye movement density (EMD) appears to be negatively related to sleep depth. Thus, EMD is depressed by sleep deprivation. We sought to determine in 19 young normal (YN) and 19 elderly normal (EN) subjects: (a) whether EMD is correlated with delta EEG in baseline sleep; (b) whether EMD is increased by daytime naps; and (c) whether EMD patterns across sleep cycles differ in the two age groups. Subjects participated in four separate 2-day recording sessions, each consisting of a baseline night, a daytime nap, and post nap night. EMD was measured as 0.3-2 Hz integrated amplitude (IA)/20 s stage REM. EMD was not correlated with rate of non rapid eye movement (NREM) delta production (power/min) in the baseline sleep of either group. Changes in EMD and delta power/min on post nap nights also were uncorrelated. These data indicate that very strong changes in sleep depth (state) are required to overcome the individual stability (traits) of NREM delta and eye movement density. ANOVA for EMD across REM periods 1-4 showed a significant cycle effect and a significant age x cycle interaction. These effects were mainly due to YNs having depressed EMD in the first REM period, likely due to the low arousal level early in sleep in these subjects. Compared with waking saccades the saccade eye movements of REM sleep have received little investigation. Further study of these movements could shed new light on neurophysiology of REM sleep. Such studies might also be clinically useful because the density of these movements appears to be related to depression and (independently) to cognitive function in individuals with brain impairment.

Adult↗

Deficits in smooth-pursuit eye movements after muscimol inactivation within the primate's frontal eye field.

To evaluate smooth-pursuit (SP) function in the primate frontal eye field (FEF), microinjections of muscimol, a gamma-aminobutyric acid (GABA) agonist, were used to reversibly deactivate physiologically characterized sites in FEF. SP was severely impaired by deactivation at sites in the FEF's smooth eye movement region (FEFsem) located in the fundus and posterior bank of the macaque monkey's arcuate sulcus. These SP deficits were apparent immediately after the muscimol injection and persisted for several hours but recovered by the next day. SP was most drastically and consistently impaired for directions similar to the injected site's elicited smooth eye movement direction or to the optimal SP direction for its neuronal responses. Targets moving in these directions, usually ipsilateral to the injected hemisphere, were tracked primarily with saccades after the muscimol injection, the peak SP velocity being only 10-30% of preinjection velocity. SP in other directions, including contralateral, was less strongly affected. Initial SP acceleration in response to target motion onset was also significantly diminished, generally by approximately the same proportion as peak SP velocity. In contrast, saccades were largely unaffected by muscimol injections in FEFsem; nor was there an immediate effect on SP when control sites in the saccadic region of FEF (FEFsac) were deactivated, although a SP deficit often appeared 30-60 min after FEFsac injections, possibly reflecting diffusion of muscimol into neighboring FEFsem. These reversible SP deficits produced by muscimol inactivation within FEFsem are similar to permanent deficits caused by large aspiration lesions of FEF and indicate that inclusion of FEFsem is the critical factor determining whether FEF lesions impair SP. The severity of the reversible deficits found here indicates how extremely critical FEFsem is for normal highgain SP.

Animals↗

The influence of repetitive eye movements on vergence performance.

We measured the peak velocity of convergence eye movement responses in four normal subjects before and after a large number of either repetitive vergence or repetitive saccadic eye movements. A 20% decrease in the mean value of peak velocity was observed in vergence responses after 100 repetitive step vergence eye movements. However, 100 cycles of slow sinusoidal vergence tracking did not induce any notable change in vergence dynamics. Five hundred repetitive saccadic eye movements also caused an approximately 20% decrease in peak velocity. The reduction in peak velocity was related to the number of repetitions for both vergence and saccadic fatiguing stimuli. The frequency of occurrence of double-vergences was also used as an index to monitor the influence of repetitive eye movements on convergence performance. Results showed that repetitive step convergence movements could double, or even triple, the frequency of the occurrence of double-vergence responses, while slow sinusoidal vergence tracking or repetitive saccades had no influence on the frequency of response doubles.

Convergence, Ocular↗

An area for vergence eye movement in primate frontal cortex.

To view objects at different distances, humans rely on vergence eye movements to appropriately converge or diverge the eyes and on ocular accommodation to focus the object. Despite the importance of these coordinated eye movements (the 'near response') very little is known about the role of the cerebral cortex in their control. As near-response neurons exist within the nucleus reticularis tegmenti pontis, which receives input from the frontal eye field region of frontal cortex, and this cortical region is known to be involved in saccadic and smooth-pursuit eye movements, we propose that a nearby region might play a role in vergence and ocular accommodation. Here we provide evidence from rhesus monkeys that a region of frontal cortex located immediately anterior to the saccade-related frontal eye field region is involved in vergence and ocular accommodation, and in the sensorimotor transformations required for these eye movements. We conclude that the macaque frontal cortex is involved in the control of all voluntary eye movements, and suggest that the definition of the frontal eye fields should be expanded to include this region.

Accommodation, Ocular↗

Saccadic eye movements in determination of the residual effects of the benzodiazepines.

Saccadic eye movements and the volunteers' subjective assessments were used in the determination of the residual effects of a single high evening dose of flunitrazepam 2 mg, midazolam 30 mg, and lorazepam 2.5 mg as well as in that of placebo. Sleep inducing and maintaining effects were subjectively assessed, too. Both flunitrazepam 2 mg, midazolam 30 mg, and lorazepam 2.5 mg possessed sleep inducing and increasing effects (n = 9), but in the number of nocturnal awakenings and quality of sleep no significant differences between placebo and the active medications were reported. Flunitrazepam 2 mg and lorazepam 2.5 mg produced distinct subjective residual effects thus differing from placebo and midazolam 30 mg. Despite this, saccadic eye movement recording could further differentiate midazolam 30 mg from placebo in this respect 10 hours after drug intake. After three repeated 2 mg evening doses, flunitrazepam accumulated in the serum of the volunteers (n = 6), but the effect on saccadic eye movements as well as subjective side effects began to decrease already after one day's treatment. Thus, saccadic eye movement recording proved to be a useful tool in determining the residual effects and development of tolerance of benzodiazepines. No correlation was detected between the serum levels (radioreceptor assay) and saccadic eye movement recordings or subjective residual sequelae.

Benzodiazepines↗

Interactions between cholinergic and GABAergic neurotransmitters in and around the locus coeruleus for the induction and maintenance of rapid eye movement sleep in rats.

The noradrenergic "REM-off" neurons in the locus coeruleus cease firing, whereas some cholinergic and non-cholinergic "REM-on" neurons increase firing during rapid eye movement sleep. A reciprocal interaction between these neurons was proposed. However, acetylcholine did not inhibit neurons in the locus coeruleus. Nevertheless, since GABA levels increase during rapid eye movement sleep and picrotoxin injections into the locus coeruleus reduced rapid eye movement sleep, it was hypothesized that GABA in the locus coeruleus might play an intermediary inhibitory role for rapid eye movement sleep regulation. Therefore, the effects of GABA or carbachol (a mixed cholinergic agonist receptor) alone, as well as an agonist of one in presence of an antagonist of the other, in the locus coeruleus were investigated on sleep-wakefulness and rapid eye movement sleep. The cholinergic agonist carbachol increased, while the muscarinic antagonist receptor scopolamine decreased, the frequency of induction of rapid eye movement sleep per hour. In contrast, GABA and picrotoxin increased and decreased, respectively, the duration of rapid eye movement sleep per episode. However, when carbachol was injected in the presence of picrotoxin or GABA was injected in the presence of scopolamine, the effect of GABA or picrotoxin was dominant. Microinjection of both scopolamine and picrotoxin in combination reduced both the frequency of initiation as well as the duration per episode of rapid eye movement sleep. From these results we suggest that in the locus coeruleus cholinergic input modulates the frequency of induction of rapid eye movement sleep and this action is mediated through GABA interneurons, whereas the length of rapid eye movement sleep per episode is maintained by the presence of an optimum level of GABA. A model of neural connections for initiation and maintenance of rapid eye movement sleep is proposed and discussed.

Acetylcholine↗

Dopamine D3 receptor (DRD3) gene polymorphism is associated with the intensity of eye movement disturbances in schizophrenic patients and healthy subjects.

Altered dopamine neurotransmission and eye movement disturbances have been implicated in the pathogenic process of schizophrenia. So far, molecular genetic studies have shown little association between schizophrenia and polymorphism of any dopamine receptor or transporter genes except for some findings concerning D3 receptor (DRD3) gene. Eye movement disturbances occur in a majority of patients with schizophrenia and in a proportion of their first-degree relatives and they have been suggested as a phenotypic marker in genetic studies of this illness. Here we report an association between the Ser9Gly polymorphism of the DRD3 gene and the intensity of eye movement disturbances (fixation and smooth pursuit) observed in 119 schizophrenic patients and in 94 unrelated healthy control subjects. In schizophrenic patients, the mean intensity of both kinds of eye movement disturbances was highest in individuals with the Ser-Ser genotype, significantly lower in Ser-Gly and lowest in the Gly-Gly genotype. The Ser-Ser genotype was more prevalent in patients with a higher intensity of both fixation (58.1 vs 23.9% P < 0.001) and smooth pursuit disturbances (52.3 vs 25.8%, P < 0.02) and the Ser-Gly genotype frequency was lower in patients with higher fixation disturbances (37.0 vs 60.9%, P < 0.02). In control subjects, the genotype frequency Ser-Ser was higher in subjects with any degree of eye movement disturbances compared to subjects without such disturbances both for fixation and smooth pursuit performance (81.0 vs 50.7%, P < 0.05 and 79.2 vs 50.0%, P < 0.05, respectively). In control subjects the frequency of Ser-Gly was lower in the first group, for either fixation or smooth pursuit, compared to normal performers (9.5 vs 43.8%, P < 0.01 and 8.3 vs 45.7, P < 0.005, respectively). We suggest that the DRD3 Ser9Gly polymorphism may be a contributing factor to the performance of eye movements used as a phenotypic marker of schizophrenia.

Adolescent↗

Eye movements during sleep in weightlessness.

The number of eye movements during sleep increased during the first sleep period in zero gravity but returned to normal by the second night. These rapid-eye-movement functions in flight may be the first variations of an oscillatory system. The ratio of the higher and lower eye movement frequencies oscillates within normal-gravity limits.

Eye Movements↗

[Disorders of eye movements in degenerative diseases of the nervous system].

Eye movement disorders detected by oculography indicate abnormal function of specific brain areas involved in the motor control. Registration of conjugate eye movement can be very useful diagnostic tool to study neurodegenerative disorders of the brain. In some conditions oculographic registration may reveal eye movement abnormalities in subclinical stages of the disease.

Alzheimer Disease↗

Eye movement abnormalities in systemic lupus erythematosus.

OBJECTIVE: To describe eye movement abnormalities in patients with systemic lupus erythematosus (SLE). DESIGN: Between January 1, 1970, and June 30, 1995, 113 patients with a clinical diagnosis of SLE were examined. Of these, 33 had ocular motor abnormalities and a diagnosis of SLE as defined by the revised criteria of the American College of Rheumatology. SETTING: Patients hospitalized on the wards of the Los Angeles County-University of Southern California Medical Center, Los Angeles. SUBJECTS: Thirty-three patients, 82% women, ranging in age from 19 to 58 years (mean, 33.5 years). The average duration of SLE was 3.5 years, and 10 patients had been symptomatic for 5 years or longer. RESULTS: Of 55 ocular motor signs, 33 involved limitation of eye movements or abnormal eye position at rest; abnormal spontaneous eye movements occurred 12 times; ptosis was seen in eight patients and psychogenic signs in two. Sixteen patients (48%) had brain-stem infarcts; 11 had other known causes, including three with meningitis, two with hysteria, and one each with ocular myositis, pseudotumor cerebri, both ocular myositis and pseudotumor cerebri, Guillain-Barré syndrome, hyperosmolality, and hypoxic encephalopathy. In four patients with isolated sixth nerve palsies and two with isolated ptosis, the cause remained unknown. CONCLUSIONS: Ocular motor signs in SLE are uncommon and often transitory. When present, they help to ascertain the location, and often the cause, of neurologic involvement.

Adult↗