Saccadic system functioning among schizophrenia patients and their first-degree biological relatives.

In Study 1, 30 schizophrenia Ss and 27 nonpsychiatric comparison Ss were presented with a fixation task, a visually guided reflexive saccade (prosaccade) task, a predictive tracking task (0.4-Hz square wave), and an antisaccade task. The 2 groups did not differ on either the fixation or prosaccade tasks. Schizophrenia Ss had an increased number of errors on the antisaccade task and had decreased rightward visually guided saccade amplitudes during the predictive tracking task. In Study 2, 13 psychiatric comparison Ss and 32 1st-degree biological relatives of the schizophrenia Ss were compared with the schizophrenia Ss and a larger and older sample of nonpsychiatric Ss (n?=?33) on the predictive tracking and antisaccade tasks. The groups did not differ on predictive saccadic tracking. The schizophrenia Ss and their 1st-degree biological relatives made more errors on the antisaccade task than both the nonpsychiatric and psychiatric comparison groups (who did not significantly differ). Results are consistent with the notion that dysfunction of dorsolateral prefrontal cortex, caudate nucleus, or both is related to liability for schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Saccadic eye movements in families multiply affected with schizophrenia: the Maudsley Family Study

OBJECTIVE: Family studies have shown that abnormalities of smooth pursuit eye movement are increased in the adult relatives of schizophrenic probands as well as in the probands themselves. More recently, an inability of schizophrenic subjects to inhibit reflexive saccades reliably has been shown. This study aimed to test the hypothesis that the latter dysfunction is part of the extended schizophrenia phenotype. METHOD: With the use of infrared oculography, measurements of reflexive saccades and antisaccades were undertaken in 29 probands with schizophrenia, 50 of their nonpsychotic first-degree relatives, and 38 unrelated healthy volunteers. RESULTS: Probands, relatives, and healthy subjects showed no overall differences in the generation of reflexive saccades. However, in the antisaccade task, probands showed more saccadic distractibility when they were required to inhibit reflexive saccades. Analysis of corrective saccades showed that this was not due to failed comprehension or motivation. Relatives of the probands with high saccadic distractibility showed a higher distractibility rate than relatives of the probands with normal distractibility. Across all subjects, females showed a higher rate of distractibility errors than males. CONCLUSIONS: The ability to suppress reflexive saccades is an objective neurocognitive measure that is impaired in schizophrenic patients and in a proportion of their biological relatives. This antisaccade abnormality may be a vulnerability marker in a subset of schizophrenic patients and their families.     

Value of beat-to-beat blood pressure changes, detected by pulse transit time, in the management of the obstructive sleep apnoea/hypopnoea syndrome

BACKGROUND: Previous studies of oculomotor dysfunction in schizophrenia have tended to concentrate on abnormalities of smooth pursuit eye tracking in chronic medicated patients. We report the results of a study of smooth pursuit, reflexive and antisaccade performance in drug naive and antipsychotic treated first-episode schizophrenic patients. METHODS: Smooth pursuit and saccadic eye movements were recorded in 36 first-episode schizophrenic patients and 36 controls matched for age and estimated IQ. The schizophrenic patients were divided into drug-naive (N = 17) and antipsychotic treated groups (N = 19). RESULTS: Smooth pursuit velocity gain was significantly lower than controls only in the drug-naive patients. The treated patients did not differ significantly from either the controls or the untreated group. In an antisaccade paradigm both treated and drug-naive schizophrenic patients demonstrated an increased number of errors, but only drug-naive patients also demonstrated an increased latency in initiating correct antisaccades. CONCLUSIONS: These impairments are unlikely to be due to a generalized deficit in oculomotor function in the schizophrenic groups, as there were no differences between the groups in saccadic metrics on a reflexive saccade task. The results show that both smooth pursuit and saccadic abnormalities are present at the onset of schizophrenia and are integral to the disorder.     

What Is Perseverated in Schizophrenia? Evidence of Abnormal Response Plasticity in the Saccadic System.

Although perseveration is sometimes attributed to defective set switching, the authors have recently shown that set-switching is normal in schizophrenia. In this article, the authors tested for persistent states of the saccadic response system, rather than set perseveration. Schizophrenic and healthy subjects performed antisaccades and prosaccades. The authors analyzed for 3 carry-over effects. First, whereas the latency of the current saccade correlated with that of the prior saccade in both groups, the correlations under mixed-task conditions declined in healthy but not in schizophrenic subjects. Second, antisaccades in penultimate trials delayed upcoming saccades in schizophrenic but not in healthy subjects. Third, schizophrenic subjects were more likely to erroneously perseverate the direction of a prior antisaccade but not a prior prosaccade. The authors concluded that, in schizophrenia, the effects of correct antisaccades are persistent not weak. Saccades in schizophrenia are characterized by perseveration of antisaccade-induced changes in the saccadic response system rather than failures to switch task set. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decrease in saccadic performance after many visually guided saccadic eye movements in monkeys

PURPOSE: To investigate the influence of repeated saccades and of background illumination on the metrics and dynamics of visually guided targeting saccades. METHODS: Eye movements were measured by magnetic search coil technique in seven trained monkeys (Macaca mulatta) while they performed many visually guided saccades in the dark or in dim background light. RESULTS: After 2000 to 7000 saccades in the dark, peak eye velocity on the average decreased by 20%, saccadic gain decreased slightly by 4.5%, and saccadic latency increased by 15%. All parameters also showed increased variability. In contrast, when testing was done in dim light, there was little to no change in average saccadic metrics and latency. CONCLUSIONS: The changes in saccadic metrics and dynamics in the dark do not reflect a change of the ocular plant but may reflect a change in the cortical or cerebellar influences on the brain stem burst generator linked to the monkeys attentional state. Background light mostly prevents this change.     

Accuracy of visually and memory-guided antisaccades in man

Primary saccades to remembered targets are generally not precise, but rather undershoot target position. The major source of this saccadic undershoot may be (a) a memory-related process or (b) a poor spatial resolution in those processes which transfer the retinotopic target information into an intermediate memory-linked representation of space. The aim of this study was to investigate whether distortions of eye positions in the antisaccade task, which are characterized by inherent co-ordinate transformation processes, may completely account for the spatial inaccuracies of memory-guided antisaccades. The results show that the spatial inaccuracy of primary and secondary eye movements in the visually guided antisaccade task was comparable to that in the memory-guided antisaccade task. In both conditions, the direction error component was less dysmetric than the amplitude error component. Secondary eye movements were significantly corrective. This increase of eye position accuracy was achieved by reducing the amplitude error only. It is concluded from this study that at least some of the distortion of memory-guided saccades is due to inaccuracies in the sensorimotor co-ordinate transformations.     

Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist with psychotogenic and dissociative effects in healthy humans. These cognitive and perceptual effects in humans are reportedly reduced by benzodiazepine premedication. This study assessed the interactive effects of a ketamine (i.v. bolus of 0.26 mg/kg followed by an infusion of 0.65 mg/kg per hour) and lorazepam 2 mg., PO, in humans. Twenty-three healthy subjects completed 4 test days involving the oral administration of lorazepam or matched placebo 2 h prior to the i.v. infusion of ketamine or placebo. Ketamine: 1) produced behaviors similar to the positive and negative symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale (BPRS); 2) evoked perceptual alterations as measured by the Clinician-Administered Dissociative States Scale (CADSS); 3) impaired performance on the Wisconsin Card Sorting Test (WCST) and other tests sensitive to frontal cortical impairment; and 4) had amnestic effects. Lorazepam produced attention impairments, concrete proverb interpretations, and recall impairments. Lorazepam reduced ketamine-associated emotional distress and there was a non-significant trend for it to decrease perceptual alterations produced by ketamine. However, it failed to reduce many cognitive and behavioral effects of ketamine, including psychosis. Further, lorazepam exacerbated the sedative, attention-impairing, and amnestic effects of ketamine. There was no evidence of pharmacokinetic interaction between these medications. These data suggest that subhypnotic lorazepam and ketamine show a spectrum of interactive effects, ranging from antagonism to potentiation.     

Antisaccade task performance in questionnaire-identified schizotypes

Individuals who scored high on Perceptual Aberration-Magical Ideation Scales (Per-Mag; n = 90), the Social Anhedonia Scale (SocAnh; n = 39), and control participants (n = 89) were administered saccadic refixation (prosaccade) and saccadic suppression (antisaccade) tasks. Eye movements were scored in terms of error rates and latency. None of the groups differed in terms of their performance on the prosaccade task. Both the Per-Mag (p < 0.01) and SocAnh (p < 0.05) groups exceeded the controls in terms of mean antisaccade errors. The high-risk groups did not differ from each other. Eighteen of the Per-Mag individuals and 10 of the SocAnh individuals displayed deviant antisaccade performance. These findings are particularly interesting in light of suggestive evidence that antisaccade task deficits may serve as a marker of susceptibility to schizophrenia. It is hypothesized that the individuals who scored aberrantly on the Chapman scales and displayed antisaccade performance deficits are most likely to be at risk for the development of psychosis.     

Age differences in saccadic averaging.

Younger and older adults were asked to saccade to an orientation-defined target that was presented alone, with a more central distractor, or with a more peripheral distractor. Both age groups exhibited saccadic averaging that was more pronounced in the central distractor condition, wherein older adults had the larger effect. These results are relevant to questions of oculomotor control and also have implications for the study of age differences in other visually guided behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibitory inefficiency and failures of intention activation: Age-related decline in the control of saccadic eye movements.

Young and older adults' control of saccadic eye movements was compared using an antisaccade task, which requires the inhibition of a reflexive saccade toward a peripheral onset cue followed by an intentional saccade in the opposite direction. In 2 experiments, an age-related decline was found in the suppression of reflexive eye movements, as indicated by an increased proportion of saccades toward the cue, and a longer time needed to initiate correct antisaccades. The results from Experiment 2 suggested that older adults' slower antisaccades may be explained partly in terms of increased failures to maintain the cue-action representation at a sufficient activation level. The results suggest that the notion of selective preservation with age of the ability to inhibit spatial responses does not apply to the active inhibition of prepotent spatial responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ten years of experience with the modified Ross procedure

BACKGROUND: Abnormal performance on the antisaccade task suggests that patients with schizophrenia have difficulty with the inhibition of reflexive attentional shifts. The aim of the study was to investigate whether deficits in the inhibition of reflexive attentional shifts were specific to the oculomotor modality or whether they could also occur when attentional shifts were made without eye movements (e.g. covert attentional shifts). METHODS: Fifteen medicated patients with chronic schizophrenia and 15 matched controls performed the antisaccade task and the covert orientating task (COVAT) where the probability of targets appearing at the same location of a peripheral cue was varied so that voluntary and reflexive orientating systems had the same goal (80% probability of target and cued condition) or opposite goals (20% probability of target at cued location). A condition where only reflexive orientating was initiated was also included (50% probability of target at cued location). For each of these conditions the stimulus onset asynchrony (SOA) varied between 150 and 350 ms. RESULTS: Patients with schizophrenia showed normal latency and accuracy for visually guided saccades but increased error rates and latency on the antisaccade task. For the COVAT, patients with schizophrenia were unable to use voluntary orientating strategies to inhibit reflexive shifts of covert attention. On conditions where only reflexive orientating was required or when the goals of the reflexive and voluntary orientating systems were the same, patients with schizophrenia showed normal performance. CONCLUSIONS: These results suggest the reflexive orientating mode is normal in patients with chronic schizophrenia. However, these patients have a reduced ability to utilize the voluntary orientating mode to control or inhibit reflexive orientating. This impairment of voluntary control is evident for both overt and covert attentional shifts.     

Saccadic eye movement and working memory deficits following damage to human prefrontal cortex

A patient with a lesion confined largely to the right inferior frontal gyrus was found to be impaired on tests of spatial working memory and executive functioning. By contrast, his pattern recognition was good. The patient's selective impairments are consistent with the view that prefrontal cortex contributes to processes involved in spatial working memory. The patient was also tested on a range of oculomotor paradigms, some of which required the temporary suppression of a saccadic response. He was unable to suppress making contra- or ipsilesional reflexive glances to peripheral stimuli on the "anti-saccade" paradigm, but his performance improved on delayed saccade, memory-guided saccade and fixation tasks. Although reflexive glances were observed under these conditions they occurred more frequently in response to contralesional stimuli than ipsilesional ones. Furthermore, the patient had no difficulty in performing anti-point movements with his ipsilesional hand. Thus, his inability to suppress reflexive glances on the anti-saccade task is not due to a generalised problem of "distractibility". The patient's deficits are discussed in terms of models of anti-saccade generation and are related to recent findings regarding the role of prefrontal cortex in working memory and visual attention.     

Antisaccade performance predicted by neuronal activity in the supplementary eye field

The voluntary control of gaze implies the ability to make saccadic eye movements specified by abstract instructions, as well as the ability to repress unwanted orientating to sudden stimuli. Both of these abilities are challenged in the antisaccade task, because it requires subjects to look at an unmarked location opposite to a flashed stimulus, without glancing at it. Performance on this task depends on the frontal/prefrontal cortex and related structures, but the neuronal operations underlying antisaccades are not understood. It is not known, for example, how excited visual neurons that normally trigger a saccade to a target (a prosaccade) can activate oculomotor neurons directing gaze in the opposite direction. Visual neurons might, perhaps, alter their receptive fields depending on whether they receive a pro- or antisaccade instruction. If the receptive field is not altered, the antisaccade goal must be computed and imposed from the top down to the appropriate oculomotor neurons. Here we show, using recordings from the supplementary eye field (a frontal cortex oculomotor centre) in monkeys, that visual and movement neurons retain the same spatial selectivity across randomly mixed pro- and antisaccade trials. However, these neurons consistently fire more before antisaccades than prosaccades with the same trajectories, suggesting a mechanism through which voluntary antisaccade commands can override reflexive glances.     

Abnormal saccadic distractibility in patients with schizophrenia: a 99mTc-HMPAO SPET study

Recent research has shown that some patients with schizophrenia have a severe impairment in the suppression of reflexive saccadic eye movements in the ANTI-saccade task. This saccadic distractibility has previously been found in patients with lesions of dorsolateral prefrontal cortex, implicating an abnormality of prefrontal cortex. The objective of the present study was to determine the contribution of these and other areas to the ANTI-saccadic abnormality in schizophrenia by functional neuroimaging. Using 99mtechnetium-HMPAO high resolution multidetector single-photon emission tomography, regional cerebral blood flow (rCBF) during performance of the ANTI-saccade eye-movement task was compared, by statistical parametric mapping, in ten male schizophrenic patients on stable antipsychotic medication who had a high distractibility error rate on the task, and eight similar patients who had normal distractibility error rates. Compared with the normal error group, the patients with high error rates showed significantly decreased rCBF bilaterally, in the anterior cingulate, insula, and in left striatum. These same patients also had increased perseverative errors on the Wisconsin Card Sort Test.     

Parallel allocation of attention prior to the execution of saccade sequences.

In a series of 5 experiments, the allocation of attention prior to the execution of saccade sequences was examined by using a dual-task paradigm. In the primary task, participants were required to execute a sequence of 2 endogenous saccades. The secondary task was a forced-choice letter identification task. During the programming of the saccade sequences, letters were briefly presented at the saccade goals and at no-saccade locations. The results showed that performance was better for letters presented at any of the saccade goals than for letters presented at any of the no-saccade locations. The results support a spatial model that assumes that prior to the execution of a saccade sequence, attention is allocated in parallel to all saccade goals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prefrontal and cerebellar abnormalities in major depression: evidence from oculomotor studies

BACKGROUND: Neurobehavioral studies have identified multiple cognitive and motor system disturbances in depressed patients. Neuroimaging studies have identified abnormalities in neocortex, striatum, and cerebellar vermis that are probable causes of these impairments. METHODS: To further clarify the origins of motor and cognitive disturbances in major depression, unmedicated depressed inpatients (n = 29) and an age- and gendermatched healthy comparison group (n = 19) were tested with a battery of oculomotor tasks selected to assess the functional integrity of frontostriatal circuitry and the cerebellar vermis. RESULTS: Depressed patients demonstrated increased rates of response suppression errors on an antisaccade task, less accurate memory for spatial location information in a spatial delayed response task, dysmetric visually guided saccades, and increased rates of saccadic intrusions during visual fixation. CONCLUSIONS: These results provide quantitative documentation of significant disturbances in neurophysiological processes subserved by prefrontal cortex and the cerebellar vermis during episodes of major depression.     

Nucleotide sequences and functional characterization of two tobacco UAG suppressor tRNA(Gln) isoacceptors and their genes

The hypothesis was tested that peak velocity of saccadic eye movements in visual motor tasks varies with variables related to energy regulation. The hypothesis is based on the cognitive-energetical performance model of Sanders. An experimental paradigm was developed in which saccadic peak velocity of task-relevant eye movements is measured while a choice reaction task is carried out. Confounding factors of saccadic amplitude and movement direction were controlled. The task was designed in such a way that in each trial subjects performed a target saccade towards an imperative stimulus and a return saccade after the manual response back to the centre of the screen. For both types of saccades the experimental variables were foreperiod duration (short versus long), knowledge of results (with versus without), postsaccadic demand (low versus high) and time on task (five 30-min intervals). In two experiments, there are main and interaction effects of the task variables on peak saccadic velocity. Return saccades are slower than target saccades, but not in the case of high postsaccadic demand. Knowledge of results increases peak saccadic velocity, but more so for return than for target saccades. Time on task leads to a decrease in peak saccadic velocity, which is much stronger for return than for target saccades; furthermore this effect is more pronounced after short than after long foreperiods. Peak saccadic velocity is changed within seconds. The results support the hypothesis. Peak saccadic velocity of task related eye movements reflects energy regulation during task performance. The paradigm will be developed as a diagnostic tool in workload measurement.     

Understanding the function of visual short-term memory: Transsaccadic memory, object correspondence, and gaze correction.

Visual short-term memory (VSTM) has received intensive study over the past decade, with research focused on VSTM capacity and representational format. Yet, the function of VSTM in human cognition is not well understood. Here, the authors demonstrate that VSTM plays an important role in the control of saccadic eye movements. Intelligent human behavior depends on directing the eyes to goal-relevant objects in the world, yet saccades are very often inaccurate and require correction. The authors hypothesized that VSTM is used to remember the features of the current saccade target so that it can be rapidly reacquired after an errant saccade, a task faced by the visual system thousands of times each day. In 4 experiments, memory-based gaze correction was accurate, fast, automatic, and largely unconscious. In addition, a concurrent VSTM load interfered with memory-based gaze correction, but a verbal short-term memory load did not. These findings demonstrate that VSTM plays a direct role in a fundamentally important aspect of visually guided behavior, and they suggest the existence of previously unknown links between VSTM representations and the occulomotor system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distinguishing schizophrenic patients from healthy controls by quantitative measurement of eye movement parameters

BACKGROUND: Eye tracking dysfunction is a putative trait marker for susceptibility to schizophrenia; however, it cannot be recommended as an additional tool for the diagnosis of schizophrenia, due to low sensitivity and specificity. METHODS: To assess the diagnostic potentials of combinations of eye movement paradigms, four smooth pursuit experiments (1: constant velocity of 15 degrees/sec; 2 and 3: combination with either visual or auditory distractors; 4: constant velocity of 30 degrees/sec) and two saccadic eye movement experiments (1: reflexive saccades; 2: voluntary saccades) were conducted. Fourteen patients with residual schizophrenia and 17 healthy controls were studied. Two sets of discriminant analyses (each with the resubstitution and with the "leaving one out" method) were calculated. RESULTS: In the first set, all 10 characteristic variables were included, whereas for the second set, the three most powerful parameters were selected (two from smooth pursuit tasks and one from a voluntary saccade experiment). This procedure provided the best classification results, regarding concordance between clinical diagnoses and eye movement dysfunction (kappa = .67-.80). CONCLUSIONS: Schizophrenic patients of the residual subtype can be differentiated from healthy individuals with considerable criterion validity on the basis of paradigms from two different ocular motor systems.     

Apparent decrease in population clearance of theophylline: implications for dosage

Tthe antisaccade eye movement task, which has been linked to frontal lobe function, presents a target in one visual field and asks subjects to move their eyes to the same location in the opposite field. The task requires inhibition of the reflexive prosaccade to the cue, initiation of the antisaccade to the opposite field, and visuo-spatial memory of the cue location. Forty-two subjects from 19-79 years of age performed this task and a control task, visually guided saccades to the cue itself, to determine which functions are affected by aging. The time to initiate antisaccades increased linearly with age at a rate greater than the time to initiate visually guided saccades. This difference suggests that the processing time to inhibit the incorrect movement to the cue is selectively increased with age. Older subjects also made more incorrect prosaccadic movements to the cue, a finding consistent with the loss of inhibitory processing capacity. The accuracy of movements did not change, which suggests that visuo-spatial memory is unaffected by aging.