Eye Movements In Schizophrenia Research Articles

Compromised Neural Circuit Dynamics Underlying Impaired Control of Eye Movements in Schizophrenia

Compromised Neural Circuit Dynamics Underlying Impaired Control of Eye Movements in Schizophrenia

In the eye of the beholder? Oxytocin effects on eye movements in schizophrenia

BackgroundIndividuals with schizophrenia have difficulty in extracting salient information from faces. Eye-tracking studies have reported that these individuals demonstrate reduced exploratory viewing behaviour (i.e. reduced number of fixations and shorter scan paths) compared to healthy controls. Oxytocin has previously been demonstrated to exert pro-social effects and modulate eye gaze during face exploration. In this study, we tested whether oxytocin has an effect on visual attention in patients with schizophrenia. MethodsNineteen male participants with schizophrenia received intranasal oxytocin 40UI or placebo in a double-blind, placebo-controlled, crossover fashion during two visits separated by seven days. They engaged in a free-viewing eye-tracking task, exploring images of Caucasian men displaying angry, happy, and neutral emotional expressions; and control images of animate and inanimate stimuli. Eye-tracking parameters included: total number of fixations, mean duration of fixations, dispersion, and saccade amplitudes. ResultsWe found a main effect of treatment, whereby oxytocin increased the total number of fixations, dispersion, and saccade amplitudes, while decreasing the duration of fixations compared to placebo. This effect, however, was non-specific to facial stimuli. When restricting the analysis to facial images only, we found the same effect. In addition, oxytocin modulated fixation rates in the eye and nasion regions. DiscussionThis is the first study to explore the effects of oxytocin on eye gaze in schizophrenia. Oxytocin had enhanced exploratory viewing behaviour in response to both facial and inanimate control stimuli. We suggest that the acute administration of intranasal oxytocin may have the potential to enhance visual attention in schizophrenia.

Paryakula drishti of Unmada: Deficits of smooth pursuit eye movements and anti-saccades in schizophrenia

Bhuta vidya (Ayurvedic psychiatry) is one of the eight specialties of Ayurveda. Unmada is a broad term which includes various psychiatric disorders described in modern psychiatry. The classification, etiology, pathogenesis, signs and symptoms, prognosis, and treatment of Unmada are available in all Ayurvedic classical texts. Abnormal eye movements such as “Paryakula drishti” (abnormal eye movements which denotes excitement or confusion or agitation)/“Chakshusho aakulata” (abnormal eye movements denotes confusion or perplexity)/“Chakshusho aswasthatvam” (abnormal eye movements) and “Chakshushoscha apasarpanam” (abnormal tracking) are mentioned among various signs and symptoms of Unmada. In Ayurveda, till date, no studies have been conducted, and no focus has been given on these abnormal eye movements of Unmada. The present study aims at understanding of these abnormal eye movements mentioned in Unmada with the help of modern research and literature. Abnormal smooth pursuit eye movements, decreased pursuit gain, increased saccadic frequency, increased anticipatory saccades, and anti-saccade errors are well-documented in schizophrenia patients. It seems that ancient Indian Ayurvedic sages had tremendous observational and clinical skills by which they were able to detect abnormal eye movements in the patients suffering from various psychiatric disorders thousands of years before. Various abnormal eye movements such as smooth pursuit eye movements deficits, abnormal saccadic eye movements, and other abnormal eye movements in schizophrenia resembles with “Paryakula drishti/Chakshusho aakulata/Chakshusho apasarpanam” of Unmada. Currently available research based on abnormal eye movements in schizophrenia supports the Ayurvedic view.

Efference Copy Failure during Smooth Pursuit Eye Movements in Schizophrenia

Abnormal smooth pursuit eye movements in patients with schizophrenia are often considered a consequence of impaired motion perception. Here we used a novel motion prediction task to assess the effects of abnormal pursuit on perception in human patients. Schizophrenia patients (n = 15) and healthy controls (n = 16) judged whether a briefly presented moving target ("ball") would hit/miss a stationary vertical line segment ("goal"). To relate prediction performance and pursuit directly, we manipulated eye movements: in half of the trials, observers smoothly tracked the ball; in the other half, they fixated on the goal. Strict quality criteria ensured that pursuit was initiated and that fixation was maintained. Controls were significantly better in trajectory prediction during pursuit than during fixation, their performance increased with presentation duration, and their pursuit gain and perceptual judgments were correlated. Such perceptual benefits during pursuit may be due to the use of extraretinal motion information estimated from an efference copy signal. With an overall lower performance in pursuit and perception, patients showed no such pursuit advantage and no correlation between pursuit gain and perception. Although patients' pursuit showed normal improvement with longer duration, their prediction performance failed to benefit from duration increases. This dissociation indicates relatively intact early visual motion processing, but a failure to use efference copy information. Impaired efference function in the sensory system may represent a general deficit in schizophrenia and thus contribute to symptoms and functional outcome impairments associated with the disorder.

Imagined motor action and eye movements in schizophrenia

Visual exploration and planning of actions are reported to be abnormal in schizophrenia. Most of the studies monitoring eye movements in patients with schizophrenia have been performed under free-viewing condition. The present study was designed to assess whether mentally performing an action modulates the visuomotor behavior in patients with schizophrenia and in healthy controls. Visual scan paths were monitored in eighteen patients with schizophrenia and in eighteen healthy controls. Participants performed two tasks in which they were asked either to (1) look at a scene on a computer screen (free viewing), or (2) picture themselves making a sandwich in front of a computer screen (active viewing). The scenes contained both task-relevant and task-irrelevant objects. Temporal and spatial characteristics of scan paths were compared for each group and each task. The results indicate that patients with schizophrenia exhibited longer fixation durations, and fewer fixations, than healthy controls in the free viewing condition. The patients' visual exploration improved in the active viewing condition. However, patients looked less at task-relevant objects and looked more at distractors than controls in the active viewing condition in which they were asked to picture themselves making a sandwich in moving their eyes to task-relevant objects on an image. These results are consistent with the literature on deficits in motor imagery in patients with schizophrenia and it extends the impairment to visual exploration in an action imagery task.

Effects of adjunct valproic acid on clinical symptoms and saccadic eye movements in schizophrenia

Valproic acid (VPA) has been suggested as a potential adjunct therapy in schizophrenia for the treatment of clinical symptoms and cognitive deficits. Here, we investigate the effects of VPA on clinical symptoms and saccadic eye movements while controlling for multiple medication effects. Remitted and first-episode schizophrenia patients taking haloperidol were given adjunct VPA for approximately 2 weeks and tested using a measure of clinical symptoms (Positive and Negative Syndrome Scale) and saccadic eye movement tasks over three testing periods. The effects of VPA were compared with schizophrenia patients medicated with equivalent doses of haloperidol alone (HAL group) and normal controls. Schizophrenia patients had higher error rates on the antisaccade task (AS task) compared with normal controls. Adjunct VPA did not affect AS task error rates but was associated with an increase in response times for both saccade and AS tasks, with a significantly greater and dose-dependent increase in response times for the AS task. There were no differences in clinical improvement between VPA and HAL schizophrenia patient groups when controlling for haloperidol medication state. These results suggest that adjuvant VPA therapy results in both sensorimotor and cognitive slowing but does not either help or further impair inhibitory control in schizophrenia, as measured by the elevated AS task errors.

COMT val158met genotype and smooth pursuit eye movements in schizophrenia

The association between the catechol-O-methyltransferase (COMT) val158met polymorphism (rs4680) and smooth pursuit eye movements (SPEM) was investigated in 110 schizophrenia patients and 96 controls. Patients had lower steady-state pursuit gain and made more frequent saccades than controls. Genotype was not associated with schizophrenia or SPEM, in either group or the combined sample. SPEM deficits in schizophrenia appear to be determined by genotypes other than rs4680, although the study may have lacked power to detect small effects.

Neuregulin-1 genotypes and eye movements in schizophrenia

Neuregulin-1 (NRG-1) is a putative susceptibility gene for schizophrenia but the neurocognitive processes that may involve NRG-1 in schizophrenia are unknown. Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes, which may be associated with brain dysfunctions underlying the pathophysiology of schizophrenia. The aim of this study was to investigate the associations of NRG-1 genotypes with AS and SPEM in schizophrenia patients and healthy controls. Patients (N = 113) and controls (N = 106) were genotyped for two NRG-1 single nucleotide polymorphisms (SNPs); SNP8NRG222662, a surrogate marker for the originally described Icelandic NRG-1 risk haplotype, and SNP8NRG243177, which has recently been associated with individual differences in brain function. Subjects underwent infrared oculographic assessment of AS and SPEM. The study replicates previous findings of impaired AS and SPEM performance in schizophrenia patients (all P < 0.005; all d = 0.5-1.5). SNP8NRG243177 risk allele carriers had marginally increased variability of AS spatial error (P = 0.050, d = 0.3), but there were no significant genotype effects on other eye movement variables and no significant diagnosis-by-genotype interactions. Generally, risk allele carriers (G allele for SNP8NRG222662 and T allele for SNP8NRG243177) had numerically worse performance than non-carriers on most AS and SPEM variables. The results do not suggest that NRG-1 genotype significantly affects AS and SPEM task performance. However, the power of the sample to identify small effects is limited and the possibility of a type II error must be kept in mind. Larger samples may be needed to reliably investigate such gene effects on oculomotor endophenotypes.

Catechol-O-Methyltransferase Val158Met Polymorphism and Antisaccade Eye Movements in Schizophrenia

The catechol-O-methyltransferase (COMT) enzyme catabolizes dopamine. The val(158)met single nucleotide polymorphism (rs4680) in the COMT gene has received considerable attention as a candidate gene for schizophrenia as well as for frontally mediated cognitive functions. Antisaccade performance is a good measure of frontal lobe integrity. Deficits on the task are considered a trait marker for schizophrenia. The aim of this study was to investigate the association of COMT val(158)met polymorphism with antisaccade eye movements in schizophrenia patients and healthy controls. Schizophrenia patients (N = 105) and healthy controls (N = 95) underwent infrared oculographic assessment of antisaccades. Subjects were genotyped for COMT val(158)met and divided into 3 groups according to genotype (val/val, val/met, and met/met). Patients displayed significantly more reflexive errors, longer and more variable latency, and lower amplitude gain than controls (all P < 0.02). A greater number of val(158) alleles was associated with shorter (P = 0.045) and less variable (P = 0.028) antisaccade latency and, nonsignificantly, with lower reflexive error rate (P = 0.056). None of these variables showed a group-by-genotype interaction (P > 0.1). There were no significant associations of genotype with measures of amplitude gain or spatial error (P > 0.2). The results suggest that COMT val(158) carrier status is associated with better performance on the antisaccade task. Possible explanations of this finding are discussed.

Genetic and neuroimaging studies of antisaccade eye movements in schizophrenia

Genetic and neuroimaging studies of antisaccade eye movements in schizophrenia

157 – Catechol- O-methyltransferase polymorphism and antisaccade eye movements in schizophrenia

157 – Catechol- O-methyltransferase polymorphism and antisaccade eye movements in schizophrenia

Different extraretinal neuronal mechanisms of smooth pursuit eye movements in schizophrenia: An fMRI study

Smooth pursuit eye movements (SPEM) are necessary to follow slowly moving targets while maintaining foveal fixation. In about 50% of schizophrenic patients SPEM velocity is reduced. In this study we were interested in identifying the cortical mechanisms associated with extraretinal processing of SPEM in schizophrenic patients. During condition A, patients and healthy subjects had to pursue a constantly visible target (10°/s). During condition B the target was blanked out for 1000 ms while subjects were instructed to continue SPEM. Eye movement data were assessed during scanning sessions by a limbus tracker. During condition A, reduced SPEM velocity in patients was associated with reduced activation of the right ventral premotor cortex and increased activation of the left dorsolateral prefrontal cortex, the right thalamus and the Crus II of the left cerebellar hemisphere. During condition B, SPEM velocity was reduced to a similar extent in both groups. While in patients a decrease in activation was observed in the right cerebellar area VIIIA, the activation of the right anterior cingulate, the right superior temporal cortex, and the bilateral frontal eye fields was increased. The results implicate that schizophrenic patients employ different strategies during SPEM both with and without target blanking than healthy subjects. These strategies predominantly involve extraretinal mechanisms.

Structural neural networks subserving oculomotor function in first-episode schizophrenia

Smooth pursuit and antisaccade abnormalities are well documented in schizophrenia, but their neuropathological correlates remain unclear. In this study, we used statistical parametric mapping to investigate the relationship between oculomotor abnormalities and brain structure in a sample of first-episode schizophrenia patients (n = 27). In addition to conventional volumetric magnetic resonance imaging, we also used magnetization transfer ratio, a technique that allows more precise tissue characterization. We found that smooth pursuit abnormalities were associated with reduced magnetization transfer ratio in several regions, predominantly in the right prefrontal cortex. Antisaccade errors correlated with gray matter volume in the right medial superior frontal cortex as measured by conventional magnetic resonance imaging but not with magnetization transfer ratio. These preliminary results demonstrate that specific structural abnormalities are associated with abnormal eye movements in schizophrenia.

Neurobiology of smooth pursuit eye movement deficits in schizophrenia: an fMRI study.

Smooth pursuit eye movements are abnormal in patients with schizophrenia. The investigators used functional magnetic resonance imaging (fMRI) to compare brain hemodynamic response during a smooth pursuit eye movement task in patients with schizophrenia and healthy comparison subjects. Fourteen patients with schizophrenia and 14 healthy comparison subjects performed a smooth pursuit eye movement task while undergoing 1.5-T fMRI. Echo-planar images from the blocked design were evaluated with both a whole-brain random-effects analysis and a region-of-interest analysis. Smooth pursuit deficits were assessed outside the fMRI apparatus by using infrared oculography and were assessed during scanning by evaluating echo-planar time-series data from the eyes. Compared to the healthy subjects, the patients with schizophrenia exhibited greater activity in both posterior hippocampi and the right fusiform gyrus during smooth pursuit eye movements. The region-of-interest analysis revealed subtle activity deficits in frontal and occipital regions in the patients with schizophrenia. Smooth pursuit deficits in the subjects with schizophrenia included lower gain (eye velocity relative to target velocity) and a higher percentage of total eye movements due to anticipatory saccades, compared with the healthy subjects. The observed group differences are consistent with evidence for diminished inhibitory function in the hippocampus as well as for a disturbance in a frontotemporal network subserving smooth pursuit eye movements in schizophrenia.

Functional MRI of visual exproration and eye movements in schizophrenia

Functional MRI of visual exproration and eye movements in schizophrenia

Pharmacological Studies of Smooth Pursuit and Antisaccade Eye Movements in Schizophrenia: Current Status and Directions for Future Research

Smooth pursuit (SPEM) and antisaccade eye movements have been studied to elucidate the genetics and the pathophysiology of schizophrenia. In recent years, a rapidly growing literature has emerged on pharmacological influences on eye movements. This review focuses on pharmacological studies of the SPEM and antisaccade tasks with relevance to schizophrenia and aims to answer the particular questions: (1) whether pharmacological compounds with relevance to the treatment or pathophysiology of schizophrenia affect performance, and (2) whether SPEM or antisaccade measures may be useful in the development of novel therapeutic targets for this illness. We conclude that (i) short- or medium-term typical antipsychotic treatment of schizophrenia patients has no or little effect on either measure, (ii) treatment with clozapine appears to impair SPEM, (iii) treatment with risperidone and 5-HT2 antagonists improves schizophrenia patients antisaccade error rate deficit, (iv) anticholiner gics, ofte n use d to contr ol extr apyra midal symptoms induc ed by typical a ntipsychotics, may w orsen pe rf ormance, ( v) be nzodiaze pines impa ir SPEM and antisacc ade per for ma nce in hea lthy individuals, (vi) nicotine, selfadministered via cigarette smoking or given via experimental procedures, improves SPEM and antisaccade performance, and (vii) SPEM has the potential to be a useful phenotype for the ketamine model of psychosis, with implications for antipsychotic drug development. Finally, we discuss methodological issues pertaining to the study of eye movements in pharmacological and genetic schizophrenia research and suggest that the SPEM and antisaccade tasks may be profitably used in the development of antipsychotic drugs. Keywords: smooth pursuit eye movements, antisaccade, schizophrenia, neuroleptic, antipsychotic, treatment, endophenotype, drug development

Effects of typical and atypical antipsychotic treatment on antisaccade and prosaccade eye movements in schizophrenia

Effects of typical and atypical antipsychotic treatment on antisaccade and prosaccade eye movements in schizophrenia

Exploratory eye movements in schizophrenia

It has been reported that patients with schizophrenia show restricted eye-scanning in comparison with normal controls; however, the precise mechanism underlying the limited eye movement pattern remains unknown. The purpose of this study was to determine the factors affecting restricted eye-scanning in schizophrenic patients by examining exploratory eye movements during demonstration of two different sizes of the S-shaped figure. The second purpose was to determine the effect of the instruction for performance on the restricted viewing pattern in patients with schizophrenia. Eye movements during demonstration of the S-shaped figure of the original or half size were examined in 15 patients with schizophrenia and 15 normal controls using an infrared eye-mark recorder. The patients showed lower search scores than control subjects for both sizes of the figure. The subjects were then instructed to compare a slightly modified figure with the original one. Lower responsive search scores were found for the patients when "fixation point" was defined as a point at which a gaze was held for at least 200 ms, while the patients and control subjects performed equally at the 100-ms setting. Direct instruction to scrutinize the S-shape abolished the difference in the search scores between patients and control subjects at both the 100-ms and 200-ms settings. These findings suggest that the size of the S-figure is not a factor of restricted eye movements, and that the direct instruction improves the visual performance in patients with schizophrenia.

The misclassification of blinks as saccades: Implications for investigations of eye movement dysfunction in schizophrenia

It is important to have a simple, accurate method for recording eye movements. Of the two popular approaches commonly adopted, electro-oculography (EOG) and infrared oculography (IROG), IROG is often accepted as the more accurate, and it is the method that is currently used most frequently to examine eye movements in schizophrenia. This study investigated whether the misclassification of blinks as saccades affects saccade rates when the presence of a blink is determined using only IROG recordings of eye position. Both vertical electro-oculography (VEOG), which can be used to objectively identify blinks, and IROG were recorded while 17 schizophrenia patients and 19 healthy controls were presented with sinusoidal stimuli. Of the blinks identified with the VEOG for the total group of participants, a substantial number (37%) were misclassified as catch-up and anticipatory saccades when only the IROG was used. Furthermore, in the schizophrenia group, but not in the healthy control group, the use of the IROG led to a significant misclassification of blinks as anticipatory saccades. Therefore, when IROG alone is used to identify blinks, the misclassification of blinks as saccades is likely to introduce measurement error into estimates of saccade rates, particularly estimates of anticipatory saccade rates in schizophrenia patients.

The misclassification of blinks as saccades: Implications for investigations of eye movement dysfunction in schizophrenia

It is important to have a simple. accurate method for recording eye movements. Of the two popular approaches commonly adopted, electro-oculography (EOG) and infrared oculography (IROG), IROG is often accepted as the more accurate, and it is the method that is currently used most frequently to examine eye movements in schizophrenia. This study investigated whether the misclassification of blinks as saccades affects saccade rates when the presence of a blink is determined using only IROG recordings of eye position. Both vertical electro-oculography (VEOG), which can be used to objectively identify blinks, and IROG were recorded while 17 schizophrenia patients and 19 healthy controls were presented with sinusoidal stimuli. Of the blinks identified with the VEOG for the total group of participants, a substantial number (37%) were misclassified as catch-up and anticipatory saccades when only the IROG was used. Furthermore, in the schizophrenia group, but not in the healthy control group, the use of the IROG led to a significant misclassification of blinks as anticipatory saccades. Therefore, when IROG alone is used to identify blinks, the misclassification of blinks as saccades is likely to introduce measurement error into estimates of saccade rates, particularly estimates of anticipatory saccade rates in schizophrenia patients.