The Influence of Maternal Schizotypy on the perception of Facial Emotional Expressions during Infancy: an Event-Related Potential Study.

Parenting directly affects the developmental and clinical outcomes of children. How parental personality relates to perceptual and cognitive mechanisms during early development is not clear. For parents with traits of the personality dimension schizotypy, would their infant display brain responses similar to those on the schizophrenia-spectrum? This study investigates whether maternal personality influences early social-cognitive awareness during the first 6 postnatal months. Schizotypy is a dimension of personality within the general population. If deficits contribute to the development of schizophrenia-spectrum disorders by influencing the development of symptom-like characteristics, they may be observable in neurotypical individuals with schizotypal characteristics. Parents and their infants were shown standardised positive and negative faces and event-related potential responses were assessed. It was hypothesised that the infants of schizotypic mothers would display differential Negative-central event-related potentials for the happy and fearful expressions when compared to infants of non-schizotypic mothers. Results support prior literature; indicating 6-month-old infants allocate more attentional resources to fearful when contrasted to happy faces. The adult cohort displays this same ability. In addition, schizotypic mothers displayed comparable amplitudes for both expressions in comparison to the control mothers who exhibited larger amplitudes towards the fearful compared to the happy expression. Infants of schizotypic mothers did not show a greater sensitivity to facial expressions at 6-months, but schizotypic mothers showed a generalised response towards facial expressions compared to the typical P600 response illustrated by the control mothers. The present study suggests that development in the higher cognitive domains, such as the allocation of attention to novel stimuli, are not affected at 6 months of age by maternal personality related to schizotypy when examined at the group level. Implications for personality development, maternal-infant interactions and cognitive neuroscience methodologies are discussed.

The Effects of Previous Error and Success in Alzheimer's Disease and Mild Cognitive Impairment.

This work investigated in Alzheimer's disease dementia (AD), whether the probability of making an error on a task (or a correct response) was influenced by the outcome of the previous trials. We used the antisaccade task (AST) as a model task given the emerging consensus that it provides a promising sensitive and early biological test of cognitive impairment in AD. It can be employed equally well in healthy young and old adults, and in clinical populations. This study examined eye-movements in a sample of 202 participants (42 with dementia due to AD; 65 with mild cognitive impairment (MCI); 95 control participants). The findings revealed an overall increase in the frequency of AST errors in AD and MCI compared to the control group, as predicted. The errors on the current trial increased in proportion to the number of consecutive errors on the previous trials. Interestingly, the probability of errors was reduced on the trials that followed a previously corrected error, compared to the trials where the error remained uncorrected, revealing a level of adaptive control in participants with MCI or AD dementia. There was an earlier peak in the AST distribution of the saccadic reaction times for the inhibitory errors in comparison to the correct saccades. These findings revealed that the inhibitory errors of the past have a negative effect on the future performance of healthy adults as well as people with a neurodegenerative cognitive impairment.

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.

Parsing cognition in schizophrenia using saccadic eye movements: a selective overview.

Eye movements provide a behavioural measure of sensorimotor processing and higher cognitive functions of the brain. With the development of novel paradigms that can be used for the study of various cognitive operations, saccadic eye movements in particular, have become increasingly popular. Patients with schizophrenia have neurocognitive impairments that can be readily investigated with these paradigms. From animal, human lesion and neuroimaging studies, the cerebral centres underlying saccadic eye movements have been identified. The areas of the prefrontal cortex include the dorsolateral prefrontal cortex, the frontal eye fields, the supplementary eye fields, and the anterior cingulate cortex. Pathology of saccadic eye movements, therefore, provides information on the functional status of the underlying neural circuitry in brain disorders such as schizophrenia. In this paper, we evaluate: (i) methodological considerations that are central to the design and application of saccadic paradigms; (ii) brain activation that is associated with saccadic paradigms; (iii) recent findings in healthy subjects and schizophrenic patients; (iv) saccadic abnormalities in other psychiatric and neurological disorders and in individuals at risk for developing schizophrenia.

Cognition and the inhibitory control of saccades in schizophrenia and Parkinson's disease.

Historically, various lines of evidence have converged on the view that the brain expends much of its neural resources on inhibiting its own activity in a critical step towards the cognitive control of behaviour. The loss of inhibitory control is widely reported in neurological and psychiatric disorders; however, the consequences of reduced inhibition in terms of wider cognitive effects on cognitive control operations such as planning, abstract thought, working memory and the ability to appreciate the perspective of others ('theory of mind') has been widely overlooked. The antisaccade paradigm examines the conflict between a prepotent stimulus that produces a powerful urge to fixate the target, and the overriding goal to 'look' in the opposite direction. In this chapter we illustrate how this paradigm is increasingly used to explore the relationship of inhibitory control and cognition in Parkinson's disease, schizophrenia and healthy participants. Evidence is presented that is consistent with the theory of cognitive inhibition as a distinct process that can be dissociated from working memory. We conclude that the inhibitory control of saccadic eye movement should be studied in the wider context of cognitive operations.

Short and long term effects of antipsychotic medication on smooth pursuit eye tracking in schizophrenia.

RATIONALE: Smooth pursuit abnormalities have been observed in antipsychotic naive first-episode patients, suggesting that they are intrinsic to the illness. However, it is not clear whether these abnormalities are as severe as those observed in more chronic patients. In addition, although research suggests that there are no short-term effects of conventional antipsychotic medication, the effects of long-term antipsychotic medication on smooth pursuit eye movements are relatively unknown. OBJECTIVES: To determine the short and long term effects of antipsychotic medication on the smooth pursuit performance of first-episode and chronic patients with schizophrenia. METHODS: We compared the smooth pursuit performance of antipsychotic-treated and untreated first-episode and chronic schizophrenic patients with healthy controls using a comprehensive range of performance measures. This included velocity gain, the number, type and size of intrusive and corrective saccades, and the average time between the change in direction of the target and the change in direction of the eye movement, a measure of subjects' ability to predict target movement. RESULTS: Chronic schizophrenic patients had significantly reduced velocity gain, took longer to respond to the change in target direction and made more catch-up saccades than both first-episode schizophrenic patients and controls. First-episode patients were impaired relative to controls only on the measure of velocity gain. There were no differences between antipsychotic-naive and treated first-episode patients. Antipsychotic-free chronic patients were significantly less impaired on velocity gain than matched continuously treated chronic patients. These results were not influenced by group differences in age and symptom severity. CONCLUSIONS: These results show that: 1) the main index of smooth pursuit, velocity gain, is impaired early in the course of schizophrenia; 2) whereas velocity gain is unaffected by short-term (weeks) medication, it is worsened by chronic (years) treatment; 3) other indices of smooth pursuit, catch-up saccades and ability to predict target movement, are adversely influenced by illness chronicity rather than medication.

Abnormalities of predictive saccades in Parkinson's disease.

Saccades of patients with mild Parkinson's disease (PD) are said to be abnormal in the absence of a concurrently visible target or when they are part of a rapid sequence of eye movements. We tested this hypothesis using a predictive saccade paradigm in which target visibility is withdrawn for a period. Three rates of target alternation were used (0.25 Hz, 0.5 Hz and 1.0 Hz). Withdrawal of target visibility brought out the extremes of primary saccade gain for both the controls and the patients with PD, most undershoot being displayed at the lowest frequency, whereas the gain was greatest at the highest frequency, actually overshooting the target location. These results demonstrate that the spatial error of parkinsonian saccades does not invariably take the form of hypometria when part of a rapid sequence of eye movements.

Saccadic eye movements in essential blepharospasm.

To provide evidence of an organic pathology for essential (idiopathic) blepharospasm, reflex saccadic eye movements in response to randomly stepped visual targets were assessed in seven affected patients and seven age-matched controls using the magnetic scleral search coil technique. The results indicate a significant prolongation in latency and a reduction in gain of horizontal saccades, and an increase in latency and reduction of peak velocity of large downward saccades. These findings suggest an organic component to the aetiology of blepharospasm, the pathology of which also appears to involve the oculomotor system. The pattern of the oculomotor disorder does not allow specific localisation but is consistent with the underlying pathology being localised in the basal ganglia.

Expression of versican mRNA is developmentally regulated in the brain of the embryonic chick and the developing rat.

RNA prepared from the brains of chick embryos at 12 days of incubation contained a 12-kb transcript that hybridized with a cDNA probe for the aggregating proteoglycan versican. No transcripts were detected in the brains of newborn rats while, at 3 days of postnatal development, three sizes of transcripts were present. None were detected in the 6-day old brain and, at later stages, the smallest transcript predominated.

Spatial and temporal effects of spatial attention on human saccadic eye movements.

A spatial cueing paradigm was used to (a) investigate the effects of attentional orienting on spatial and temporal parameters of saccadic eye movements and (b) examine hypotheses regarding the hierarchical programming of saccade direction and amplitude. On a given trial, the subjects were presented with one of three peripheral cues: a "valid" cue provided correct information, a "neutral" cue no information and an "invalid" cue incorrect information about the location of the subsequent target (the cue was valid on about 50% of the trials). 100 or 500 msec after the cue onset (stimulus onset asynchrony, SOA), the eye movement target was presented at one of six possible locations (from -11.25 degrees to +11.25 degrees, at 3.75 degrees spacing). The results showed a significant effect of cueing on saccade latencies at the 100 msec, but no effect at the 500 msec SOA. The cueing benefits were restricted to the cued location; no other locations within the cued or uncued hemi-field were facilitated. The invalid trial latencies showed: (a) no advantage for targets on the same side as the cue relative to the opposite side, (b) no advantage for targets more proximal to the cue and (c) no advantage for targets sharing the same eccentricity as the cue. In a second experiment, subjects responded to the target by giving a simple manual response [simple reaction time (RT)] while keeping the eyes stationary. The results showed a significant cueing effect on simple RTs both at the 100 msec and, in contrast to saccadic eye movements, the 500 msec SOA. There were specific benefits for targets at the cued location relative to other targets within the same and opposite hemi-fields. Further, in contrast to saccades, there was a general advantage for targets within the same ("cued") hemi-field over targets in the opposite hemi-field. These findings suggest that, for saccadic eye movements (overt orienting), direction and amplitude are programmed holistically; whereas in covert orienting (with eyes stationary), motor parameters (e.g. for directed hand movements) are programmed in a more hierarchical fashion.

Increase in saccadic peak velocity with increased frequency of saccades in man.

Twelve normal subjects (aged 22-80 yr, mean 47 yr) performed three blocks of 20 saccades made to LED targets stepped back and forth. The first and last blocks were performed at a (slow) rate of 0.18 Hz, while the middle block was performed at the faster rate of 1.15 Hz. Mean saccadic amplitude was unaffected by saccade rate, but latency and duration became shorter at the higher frequency. Most interestingly, the peak velocity increased by approx. 6% when saccades were performed at the higher rate. This increase was statistically significant, even after normalization for saccade amplitude. That saccadic frequency may affect saccadic peak velocity must be considered as a potential variable when analysing saccades.

Basement membrane lectin binding sites are decreased in the esophageal endoderm during the arrival of presumptive muscle mesenchyme in the developing asteroid Pisaster ochraceus.

Basement membranes (BMs) of vertebrates and invertebrates have been shown to contain glycoproteins and proteoglycans, which include oligosaccharides and glycosaminoglycans. Lectin binding sites were characterized in the BM of gastrulating embryos of the starfish, Pisaster ochraceus. In early and mid-gastrulae, the fluorescein isothiocyanate (FITC)-lectin conjugates of concanavalin A (Con A) and wheat germ agglutinin (WGA) reveal the presence of mannose/glucose and glucosamine/sialic acid residues in the BM of all regions of the embryos. However, in the late gastrula embryo, an apparent reduction of these components is observed over the esophageal BM. Ultrastructural studies using the lectin-gold conjugates Con A, Limax flavus agglutinin (LFA), specific for sialic acid, and Dolichos biflorus agglutinin (DBA), specific for galactosamine, demonstrate that most mannose/glucose and galactosamine-containing residues lie in the lamina densa, whereas most sialic acid residues are located over the lamina lucida. In addition, a statistical analysis of lectin binding in the late gastrula embryo reveals that the amount of labelling with both Con A and LFA is significantly reduced in the esophageal region, suggesting that mannose/glucose and sialic acid residues are reduced in this region. These results confirm the observations of the FITC-lectin studies described above. They also confirm earlier studies that demonstrated a difference in BM morphology of the esophageal region (Crawford, '88). Mesenchyme cells, some of which arise from the forming coeloms (Crawford, '90), and which may represent a distinct population, colonize exclusively on this esophageal BM, where they later differentiate into muscle. Quantitative differences in BM glycoconjugates may act to direct the presumptive muscle cells to the region of the esophagus.

Multi-stepping saccadic sequences in humans.

A number of paradigms are reported in which multi-stepping saccadic sequences (MSS) are reliably elicited in normal subjects. It was observed that MSS are consistently associated with a prolongation of the initial saccade latency. Further experiments show that this phenomenon is validated across a number of independent eye movement tasks. However, the probability of MSS occurring is reduced when temporal constraints are imposed on the latency of the response. An interpretation of these task-elicited MSS in terms of the neural mechanisms controlling voluntary saccades is proposed.

Transient motion of visual texture delays saccadic eye movements.

Neurophysiological research has established that a transient stimulus, spatially located outside the receptive field of visual cells, can activate some cells and inhibit firing in others. However, the significance of this phenomenon for behavioural responses in man is unclear. This study investigated the effect of a transient peripheral event on the initiation of saccadic eye movements to a luminance increment. In Experiment 1 human saccadic eye movements to targets that varied in luminance were compared on 'shift' trials, in which the saccadic target was timed to coincide with a step displacement of a vertical grating in the background, and on 'no-shift' trials, when the background remained stationary. The results showed a significant delay in mean saccadic latencies on 'shift trials' compared to 'no-shift' trials. Saccadic latencies were reduced in both conditions with increasing target intensity. Measurement of visual sensitivity showed a small non-significant increase in thresholds in the background 'shift' condition. A second experiment manipulated visuo-temporal information by varying both target duration and intensity. This experiment revealed significant effects of target duration and signal intensity on saccadic latency; and a 3-way interaction showing that saccades suffered the greatest delay in the background 'shift' condition at the lowest duration and intensity targets. These results show that the peripheral motion of visual texture delays the programming of saccadic eye movements and there is a particularly marked effect for targets of low signal strength.

Type, location and role of glycosaminoglycans in cloned differentiated chick retinal pigmented epithelium.

In clonal culture, colonies of 3-4 week old chick retinal pigmented epithelial cells exhibit Alcian Blue positive extracellular matrix (ECM) material on the surface of the cells. Alcian blue positive ECM is located between undifferentiated cells at the edges of the disc-shaped colonies and beneath the differentiated cells in the colony center. The latter material is associated with the basement membrane. The staining properties suggest that glycosaminoglycans (GAG) are present in these regions. Extraction of GAG from homogenates of colonies, followed by electrophoresis on cellulose acetate strips, results in three bands with mobilities similar to those of hyaluronic acid, heparan sulfate, and chondroitin sulfate, respectively. All three bands label with [3H]glucosamine, and the last two also label with [35S]sulfate. The composition appeared to differ when colonies were grown in different media. Digestion of the GAG preparations with various enzymes suggests that bands II and III represent heparan sulfate and chondroitin sulfate, respectively, in colonies grown in Ham's F10g medium. The composition of band I is as yet undetermined. In minimal Eagle's medium (MEM), bands I and III consisted of hyaluronic acid and chondroitin sulfate, respectively, while band II had properties suggestive of a copolymer of heparan sulfate and an unidentified GAG. Cells release only one [3H]glucosamine-labelled GAG into the medium. This material has a mobility similar to hyaluronic acid and is digested by Streptomyces hyaluronidase, suggesting that it is hyaluronic acid. Staining with Alcian Blue at different pH suggests that it may represent the material associated with the upper surface of the cells. Some of the ECM located between the undifferentiated cells and associated with the basement membrane in the differentiated regions of the colonies stains with Alcian Blue at pH 1.0 and 0.2 suggesting that it may contain GAGs found in bands I and II. Colonies treated with medium containing 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of GAG synthesis, for 48 hr showed a reduced Alcian Blue staining of the ECM in the undifferentiated regions. After 72 hr of treatment with DON, the undifferentiated cells had detached from the plate, whereas the differentiated cells remained intact. The results suggest that the GAG may be involved in cellular adhesion, particularly of the undifferentiated cells.

Unilateral reversal of smooth pursuit and optokinetic nystagmus.

A patient is presented who has had three six-month episodes of oscillopsia over the last eight years. During the episodes, abnormal smooth pursuit and optokinetic nystagmus were noted, but there were no other abnormalities. Oculography during the most recent episode demonstrated that when tracking from right to left, the patient's smooth pursuit was reversed. There are several features of the case which suggest that the aetiology may be a form of congenital nystagmus. A possible alternative mechanism whereby such an abnormality might arise as an acquired lesion is discussed.

The perception of real and illusory motion in schizophrenia.

An illusion of rapid movement is normally perceived when an attentional cue (such as a peripheral flash) preceeds the onset of a line. The movement is perceived as receding away from the cue. This study investigated how this illusion was perceived by people with schizophrenia. Nineteen participants with schizophrenia and 26 healthy matched controls were presented with a series of real, illusory, no motion or combined real and illusory motion stimuli at various target speeds. Detection thresholds were measured to determine the reliability of motion perception. The participants with schizophrenia were not distinguished from the control group in the perception of real motion. However, the motion detection curves for the schizophrenia group revealed a reduction in the perceptual effect of illusory motion in comparison to controls. The findings revealed that people with schizophrenia may be less easily deceived by illusory motion in comparison to healthy participants.