The network structure of schizotypy in the general population.

Schizotypal personality traits show similarity with schizophrenia at various levels of analysis. It is generally agreed that schizotypal personality is multidimensional; however, it is still debated whether impulsive nonconformity should be incorporated into theories and measurement of schizotypy. In addition, relatively little is known about the network structure of the four-dimensional model of schizotypal personality. To estimate the network structure of schizotypy, we used data from participants recruited from the community (N = 11,807) who completed the short version of the Oxford-Liverpool Inventory of Feelings and Experiences, a widespread self-report instrument that assesses the positive, negative, disorganised and impulsive domains of schizotypy. We performed community detection, then examined differences between communities in terms of centralities and compared the strength of edges within and between communities. We found communities that almost perfectly corresponded to the a priori-defined subscales (93% overlap, normalised mutual information = 0.74). Items in the disorganisation community had higher closeness centrality relative to items in the other communities (Cliff's Δs ranged from 0.55 to 0.83) and weights of edges within the disorganisation community were stronger as compared to the negative schizotypy and impulsive nonconformity communities (Cliff's Δs = 0.33). Our findings imply that the inclusion of impulsive nonconformity items does not dilute the classical three-factor structure of positive, negative and disorganised schizotypy. The high closeness centrality of disorganisation concurs with theories positing that cognitive slippage and associative loosening are core features of the schizophrenic phenotype.

Following Forrest Gump: Smooth pursuit related brain activation during free movie viewing.

Most fMRI studies investigating smooth pursuit (SP) related brain activity have used simple synthetic stimuli such as a sinusoidally moving dot. However, real-life situations are much more complex and SP does not occur in isolation but within sequences of saccades and fixations. This raises the question whether the same brain networks for SP that have been identified under laboratory conditions are activated when following moving objects in a movie. Here, we used the publicly available studyforrest data set that provides eye movement recordings along with 3 â€‹T fMRI recordings from 15 subjects while watching the Hollywood movie "Forrest Gump". All three major eye movement events, namely fixations, saccades, and smooth pursuit, were detected with a state-of-the-art algorithm. In our analysis, smooth pursuit (SP) was the eye movement of interest, while saccades were acting as the steady state of viewing behaviour due to their lower variability. For the fMRI analysis we used an event-related design modelling saccades and SP as regressors initially. Because of the interdependency of SP and content motion, we then added a new low-level content motion regressor to separate brain activations from these two sources. We identified higher BOLD-responses during SP than saccades bilaterally in MT+/V5, in middle cingulate extending to precuneus, and in the right temporoparietal junction. When the motion regressor was added, SP showed higher BOLD-response relative to saccades bilaterally in the cortex lining the superior temporal sulcus, precuneus, and supplementary eye field, presumably due to a confounding effect of background motion. Only parts of V2 showed higher activation during saccades in comparison to SP. Taken together, our approach should be regarded as proof of principle for deciphering brain activity related to SP, which is one of the most prominent eye movements besides saccades, in complex dynamic naturalistic situations.

Functional connectivity during smooth pursuit eye movements.

Smooth pursuit eye movements (SPEM) hold the image of a slowly moving stimulus on the fovea. The neural system underlying SPEM primarily includes visual, parietal, and frontal areas. In the present study, we investigated how these areas are functionally coupled and how these couplings are influenced by target motion frequency. To this end, healthy participants (n = 57) were instructed to follow a sinusoidal target stimulus moving horizontally at two different frequencies (0.2 Hz, 0.4 Hz). Eye movements and blood oxygen level-dependent (BOLD) activity were recorded simultaneously. Functional connectivity of the key areas of the SPEM network was investigated with a psychophysiological interaction (PPI) approach. How activity in five eye movement-related seed regions (lateral geniculate nucleus, V1, V5, posterior parietal cortex, frontal eye fields) relates to activity in other parts of the brain during SPEM was analyzed. The behavioral results showed clear deterioration of SPEM performance at higher target frequency. BOLD activity during SPEM versus fixation occurred in a geniculo-occipito-parieto-frontal network, replicating previous findings. PPI analysis yielded widespread, partially overlapping networks. In particular, frontal eye fields and posterior parietal cortex showed task-dependent connectivity to large parts of the entire cortex, whereas other seed regions demonstrated more regionally focused connectivity. Higher target frequency was associated with stronger activations in visual areas but had no effect on functional connectivity. In summary, the results confirm and extend previous knowledge regarding the neural mechanisms underlying SPEM and provide a valuable basis for further investigations such as in patients with SPEM impairments and known alterations in brain connectivity.NEW & NOTEWORTHY This study provides a comprehensive investigation of blood oxygen level-dependent (BOLD) functional connectivity during smooth pursuit eye movements. Results from a large sample of healthy participants suggest that key oculomotor regions interact closely with each other but also with regions not primarily associated with eye movements. Understanding functional connectivity during smooth pursuit is important, given its potential role as an endophenotype of psychoses.

Smooth pursuit eye movement deficits as a biomarker for psychotic features in bipolar disorder-Findings from the PARDIP study.

OBJECTIVES: Smooth pursuit eye movement deficits are an established psychosis biomarker across schizophrenia, schizoaffective and psychotic bipolar disorder (BPwP). Whether smooth pursuit deficits are also seen in bipolar disorder without psychosis (BPwoP) is unclear. Here we present data from the Psychosis and Affective Research Domains and Intermediate Phenotypes (PARDIP) study comparing bipolar patients with and without psychotic features. METHODS: Probands with BPwP (N = 49) and BPwoP (N = 36), and healthy controls (HC, N = 71) performed eye tracking tasks designed to evaluate specific sensorimotor components relevant for pursuit initiation and pursuit maintenance. RESULTS: While BPwoP did not differ from either BPwP or HC on initial eye acceleration, they performed significantly better than BPwP on early (P < .01) and predictive (P = .02) pursuit maintenance measures, both without differing from HC. BPwP were impaired compared to HC on initial eye acceleration, and on early and predictive pursuit maintenance (all P < .01). In contrast to the three pursuit measures, BPwP and BPwoP were both impaired on general neurocognitive assessments in relation to HC (both P < .001), without a significant difference between the two bipolar patient groups. CONCLUSIONS: Our findings support the model that impairments of sensorimotor and cognitive processing as required for early and later predictive smooth pursuit maintenance are relatively specific to those bipolar patients with a history of psychosis. This suggests that the neural circuitry for developing feed-forward predictive models for accurate pursuit maintenance is associated with the occurrence of psychotic features in bipolar patients. In contrast, generalized neuropsychological impairments did not differentiate the two bipolar patient groups.

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

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

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements.

INTRODUCTION: Nicotine and methylphenidate are putative cognitive enhancers in healthy and patient populations. Although they stimulate different neurotransmitter systems, they have been shown to enhance performance on overlapping measures of attention. So far, there has been no direct comparison of the effects of these two stimulants on behavioural performance or brain function in healthy humans. Here, we directly compare the two compounds using a well-established oculomotor biomarker in order to explore common and distinct behavioural and neural effects. METHODS: Eighty-two healthy male non-smokers performed a smooth pursuit eye movement task while lying in an fMRI scanner. In a between-subjects, double-blind design, subjects either received placebo (placebo patch and capsule), nicotine (7mg nicotine patch and placebo capsule), or methylphenidate (placebo patch and 40mg methylphenidate capsule). RESULTS: There were no significant drug effects on behavioural measures. At the neural level, methylphenidate elicited higher activation in left frontal eye field compared to nicotine, with an intermediate response under placebo. DISCUSSION: The reduced activation of task-related regions under nicotine could be associated with more efficient neural processing, while increased hemodynamic response under methylphenidate is interpretable as enhanced processing of task-relevant networks. Together, these findings suggest dissociable neural effects of these putative cognitive enhancers.

Facing competition: Neural mechanisms underlying parallel programming of antisaccades and prosaccades.

The antisaccade task is a prominent tool to investigate the response inhibition component of cognitive control. Recent theoretical accounts explain performance in terms of parallel programming of exogenous and endogenous saccades, linked to the horse race metaphor. Previous studies have tested the hypothesis of competing saccade signals at the behavioral level by selectively slowing the programming of endogenous or exogenous processes e.g. by manipulating the probability of antisaccades in an experimental block. To gain a better understanding of inhibitory control processes in parallel saccade programming, we analyzed task-related eye movements and blood oxygenation level dependent (BOLD) responses obtained using functional magnetic resonance imaging (fMRI) at 3T from 16 healthy participants in a mixed antisaccade and prosaccade task. The frequency of antisaccade trials was manipulated across blocks of high (75%) and low (25%) antisaccade frequency. In blocks with high antisaccade frequency, antisaccade latencies were shorter and error rates lower whilst prosaccade latencies were longer and error rates were higher. At the level of BOLD, activations in the task-related saccade network (left inferior parietal lobe, right inferior parietal sulcus, left precentral gyrus reaching into left middle frontal gyrus and inferior frontal junction) and deactivations in components of the default mode network (bilateral temporal cortex, ventromedial prefrontal cortex) compensated increased cognitive control demands. These findings illustrate context dependent mechanisms underlying the coordination of competing decision signals in volitional gaze control.

Sleep deprivation disrupts prepulse inhibition and induces psychosis-like symptoms in healthy humans.

Translational biomarkers, such as prepulse inhibition (PPI) of the acoustic startle response, are playing an increasingly important role in the development of antipsychotic drugs for schizophrenia and related conditions. However, attempts to reliably induce a PPI deficit by psychotomimetic drugs have not been successful, leaving an unmet need for a cross-species psychosis model sensitive to this widely studied surrogate treatment target. Sleep deprivation (SD) might be such a model as it has previously been shown to induce PPI deficits in rats, which could be selectively prevented with antipsychotic but not anxiolytic or antidepressant compounds. Here, in a first proof-of-concept study we tested whether SD induces a deficit in PPI and an increase in psychosis-like symptoms in healthy humans. In two counterbalanced sessions, acoustic PPI and self-reported psychosis-like symptoms (Psychotomimetic States Inventory) were measured in 24 healthy human volunteers after a normal night's sleep and after a night of total SD. SD decreased PPI (p = 0.001) without affecting the magnitude or habituation of the startle response (all p > 0.13). SD also induced perceptual distortions, cognitive disorganization, and anhedonia (all p < 0.02). Thus, extending previous rodent work, we conclude that SD, in combination with the PPI biomarker, might be a promising translational surrogate model for psychosis as this method represents a possibility to partially and reversibly mimic the pathogenesis of psychotic states.

Neural mechanisms of smooth pursuit eye movements in schizotypy.

Patients with schizophrenia as well as individuals with high levels of schizotypy are known to have deficits in smooth pursuit eye movements (SPEM). Here, we investigated, for the first time, the neural mechanisms underlying SPEM performance in high schizotypy. Thirty-one healthy participants [N = 19 low schizotypes, N = 12 high schizotypes (HS)] underwent functional magnetic resonance imaging at 3T with concurrent oculographic recording while performing a SPEM task with sinusoidal stimuli at two velocities (0.2 and 0.4 Hz). Behaviorally, a significant interaction between schizotypy group and velocity was found for frequency of saccades during SPEM, indicating impairments in HS in the slow but not the fast condition. On the neural level, HS demonstrated lower brain activation in different regions of the occipital lobe known to be associated with early sensory and attentional processing and motion perception (V3A, middle occipital gyrus, and fusiform gyrus). This group difference in neural activation was independent of target velocity. Together, these findings replicate the observation of altered pursuit performance in highly schizotypal individuals and, for the first time, identify brain activation patterns accompanying these performance changes. These posterior activation differences are compatible with evidence of motion processing deficits from the schizophrenia literature and, therefore, suggest overlap between schizotypy and schizophrenia both on cognitive-perceptual and neurophysiological levels. However, deficits in frontal motor areas observed during pursuit in schizophrenia were not seen here, suggesting the operation of additional genetic and/or illness-related influences in the clinical disorder.

Functional magnetic resonance imaging of sensorimotor transformations in saccades and antisaccades.

Saccades to peripheral targets require a direct visuomotor transformation. In contrast, antisaccades, saccades in opposite direction of a peripheral target, require more complex transformation processes due to the inversion of the spatial vector. Here, the differential neural mechanisms underlying sensorimotor control in saccades and antisaccades were investigated using functional magnetic resonance imaging (fMRI) at 3T field strength in 22 human volunteers. We combined a task factor (prosaccades: look towards target; antisaccades: look away from target) with a parametric factor of transformation demand (single vs. multiple peripheral targets) in a two-factorial block design. Behaviorally, a greater number of peripheral targets resulted in decreased spatial accuracy and increased reaction times in antisaccades. No effects were seen on the percentage of antisaccade direction errors or on any prosaccade measures. Neurally, a greater number of targets led to increased BOLD signal in the posterior parietal cortex (PPC) bilaterally. This effect was partially qualified by an interaction that extended into somatosensory cortex, indicating greater increases during antisaccades than prosaccades. The results implicate the PPC as a sensorimotor interface that is especially important in nonstandard mapping for antisaccades and point to a supportive role of somatosensory areas in antisaccade sensorimotor control, possibly by means of proprioceptive processes.

Aberrant inhibitory control as a transdiagnostic dimension of mental disorders - A meta-analysis of the antisaccade task in different psychiatric populations.

This meta-analysis examined inhibitory control performance in the antisaccade task across mental disorders. Following PRISMA guidelines, we analyzed data from k = 146 studies (n = 13,807 participants) on antisaccade performance. Effect sizes were estimated using random-effects models and restricted maximum-likelihood estimation, with robustness tests for study heterogeneity and publication bias. Most disorders displayed elevated error rates, with schizophrenia showing the greatest impairments, followed by autism spectrum disorder, bipolar disorder and attention deficit hyperactivity disorder. Small to medium impairments were also found in eating disorders, major depressive disorder, obsessive-compulsive disorder and substance use disorder. Results were robust against corrections for publication bias and largely unaffected by confounding variables. Prolonged latencies were observed in schizophrenia, attention deficit hyperactivity disorder, bipolar disorder and obsessive compulsive disorder, with smaller and less robust effect sizes. Results indicate inhibitory control deficits in the antisaccade task across mental disorders, especially evident for error rates. While present in most disorders, results imply varying degrees of impairments, ranging from small to large in effect sizes, with largest impairments in schizophrenia.

Latent state-trait and latent growth curve modeling of inhibitory control.

The reliability of inhibitory control task performance as well as the existence of an underlying unitary inhibitory construct have been questioned. The present study is the first to use a trait and state decomposition approach to formally quantify the reliability of inhibitory control and to examine its hierarchical structure. N = 150 participants carried out antisaccade, Eriksen flanker, go/nogo, Simon, stop-signal, and Stroop tasks on three occasions. By applying latent state-trait modeling and latent growth-curve modeling, reliability was estimated and divided into the amount of variance explained by trait effects and trait changes (consistency) and the amount of variance explained by situational effects and effects of Situation × Person interaction (occasion specificity). Mean reaction times for all tasks revealed excellent reliabilities (.89-.99). Importantly, on average, 82% of variance was accounted for by consistency while specificity was rather small. Although primary inhibitory variables revealed lower reliabilities (.51-.85), the majority of explained variance was again trait determined. Trait changes were observed for most variables and were strongest when comparing the first occasion to later ones. In addition, in some variables, those improvements were particularly high in initially underperforming subjects. An analysis of the construct of inhibition on trait level showed that communality between tasks was low. We conclude that most variables in inhibitory control tasks are mainly affected by stable trait effects, but there is only little evidence of a common, underlying inhibitory control construct at trait level. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neural Correlates of Smooth Pursuit Eye Movements in Schizotypy and Recent Onset Psychosis: A Multivariate Pattern Classification Approach.

Schizotypy refers to a set of personality traits that bear resemblance, at subclinical level, to psychosis. Despite evidence of similarity at multiple levels of analysis, direct comparisons of schizotypy and clinical psychotic disorders are rare. Therefore, we used functional magnetic resonance imaging (fMRI) to examine the neural correlates and task-based functional connectivity (psychophysiological interactions; PPI) of smooth pursuit eye movements (SPEM) in patients with recent onset psychosis (ROP; n = 34), participants with high levels of negative (HNS; n = 46) or positive (HPS; n = 41) schizotypal traits, and low-schizotypy control participants (LS; n = 61) using machine-learning. Despite strong previous evidence that SPEM is a highly reliable marker of psychosis, patients and controls could not be significantly distinguished based on SPEM performance or blood oxygen level dependent (BOLD) signal during SPEM. Classification was, however, significant for the right frontal eye field (FEF) seed region in the PPI analyses but not for seed regions in other key areas of the SPEM network. Applying the right FEF classifier to the schizotypal samples yielded decision scores between the LS and ROP groups, suggesting similarities and dissimilarities of the HNS and HPS samples with the LS and ROP groups. The very small difference between groups is inconsistent with previous studies that showed significant differences between patients with ROP and controls in both SPEM performance and underlying neural mechanisms with large effect sizes. As the current study had sufficient power to detect such differences, other reasons are discussed.

Saccadic suppression in schizophrenia.

About 40% of schizophrenia patients report discrete visual disturbances which could occur if saccadic suppression, the decrease of visual sensitivity around saccade onset, is impaired. Two mechanisms contribute to saccadic suppression: efference copy processing and backwards masking. Both are reportedly altered in schizophrenia. However, saccadic suppression has not been investigated in schizophrenia. 17 schizophrenia patients and 18 healthy controls performed a saccadic suppression task using a Gabor stimulus with individually adjusted contrast, which was presented within an interval 300 ms around saccade onset. Visual disturbance scores were higher in patients than controls, but saccadic suppression strength and time course were similar in both groups with lower saccadic suppression rates being similarly related to smaller saccade amplitudes. Saccade amplitudes in the saccadic suppression task were reduced in patients, in contrast to unaltered amplitudes during a saccade control task. Notably, smaller saccade amplitudes were related to higher visual disturbances scores in patients. Saccadic suppression performance was unrelated to symptom expression and antipsychotic medication. Unaltered saccadic suppression in patients suggests sufficiently intact efference copy processing and backward masking as required for this task. Instead, visual disturbances in patients may be related to restricted saccadic amplitudes arising from cognitive load while completing a task.

Mechanisms of smooth pursuit eye movements in schizotypy.

Several studies suggest that highly schizotypal individuals display a deficit in smooth pursuit eye movements (SPEM), which are considered an important biomarker of schizophrenia. In schizophrenia, abnormal SPEM is thought to be driven by impairments in motion perception. In schizotypy, the processes underlying reduced SPEM performance have not been examined so far, and there are no studies on motion perception deficits in schizotypy. Thus, in this registered report, we aimed to investigate whether motion perception is impaired in highly schizotypal individuals, and how it contributes to SPEM performance. On an exploratory basis, we were interested in the association between schizotypy and prediction, another mechanism underlying SPEM. To address this issue, participants with high total scores of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE short form) and control participants with low scores (N = 86 in each group) performed a standard sinusoidal SPEM task, random dot kinematograms to measure motion perception, and a blanking SPEM task to assess prediction abilities. Group comparisons as well as mediator analyses were carried out to identify whether motion perception or prediction are responsible for SPEM performance in schizotypy. We found reduced blanking SPEM performance in schizotypes compared to controls, but no group differences regarding sinusoidal SPEM and motion perception. Although no significant mediators were identified for SPEM performance in schizotypes, an exploratory analysis revealed an association between motion perception and SPEM gain in high, but not in low schizotypy. Our findings imply that despite the schizotypy-related impairment in prediction, motion perception seems to be a more important predictor of SPEM performance in schizotypes. A deficit in prediction that does not relate to SPEM performance suggests that protective factors (e.g., other cognitive processes) might operate in schizotypal individuals to maintain SPEM performance on a healthy level.

Effects of nicotine on smooth pursuit eye movements in healthy non-smokers.

RATIONALE: The non-selective nicotinic acetylcholine receptor (nAChR) agonist nicotine has been argued to improve attention via enhanced filtering of irrelevant stimuli. Here, we tested this hypothesis in the context of smooth pursuit eye movements (SPEMs), an oculomotor function previously shown to improve with nicotine in some but not all studies. OBJECTIVES: In order to test whether nicotine improves performance particularly when the inhibition of distracting stimuli is required, SPEM was elicited in conditions with or without peripheral distractors. Additionally, different target frequencies were employed in order to parametrically vary general processing demands on the SPEM system. METHODS: Healthy adult non-smokers (N = 18 females, N = 13 males) completed a horizontal sinusoidal SPEM task at different target frequencies (0.2 Hz, 0.4 Hz, 0.6 Hz) in the presence or absence of peripheral distractors in a double-blind, placebo-controlled, cross-over design using a 2 mg nicotine gum. RESULTS: Nicotine increased peak pursuit gain relative to placebo (p < .001), but an interaction with distractor condition (p = .001) indicated that this effect was most pronounced in the presence of distractors. Catch-up saccade frequency was reduced by nicotine (p = .01), particularly at higher target frequencies (two-way interaction, p = .04). However, a three-way interaction (p = .006) indicated that the reduction with nicotine was strongest at the highest target frequency (0.6 Hz) only without distractors, whereas in the presence of distractors, it was strongest at 0.4-Hz target frequency. There were no effects of nicotine on subjective state measures. CONCLUSIONS: Together, these findings support a role of both distractor inhibition and general processing load in the effects of nicotine on smooth pursuit.

Combining trait and state model systems of psychosis: The effect of sleep deprivation on cognitive functions in schizotypal individuals.

Model systems of psychosis play an important role in pathophysiology and drug development research. Schizotypal individuals display similar cognitive impairments as schizophrenia patients in several domains. Therefore, schizotypy may be interpreted as a trait model system of psychosis. In addition, experimentally controlled sleep deprivation is a putative state psychosis model that evokes subclinical psychosis-like states. We aimed to further validate these model systems by examining them in relation to central cognitive biomarkers of schizophrenia. Most of all, we were interested in investigating, for the first time, effects of their combination on cognitive function. Healthy subjects with high (N = 17) or low (N = 19) levels of schizotypy performed a cognitive task battery after one night of normal sleep and after 24 h of sleep deprivation. Sleep deprivation impaired performance in the go/nogo and n-back tasks relative to the normal sleep control condition. No differences between groups or interactions of group with sleep condition were found. The role of sleep deprivation as a model of psychosis is thus supported to some extent by impairments in inhibitory control. However, classical measures of cognition may be less able to detect deficits in schizotypy, in line with evidence of more basic information processing dysfunctions in schizotypy.

Association of Schizotypy With Dimensions of Cognitive Control: A Meta-Analysis.

Schizotypy is defined as a time-stable multidimensional personality trait consisting of positive, negative, and disorganized facets. Schizotypy is considered as a model system of psychosis, as there is considerable overlap between the 2 constructs. High schizotypy is associated with subtle but fairly widespread cognitive alterations, which include poorer performance in tasks measuring cognitive control. Similar but more pronounced impairments in cognitive control have been described extensively in psychosis. We here sought to provide a quantitative estimation of the effect size of impairments in schizotypy in the updating, shifting, and inhibition dimensions of cognitive control. We included studies of healthy adults from both general population and college samples, which used either categorical or correlative designs. Negative schizotypy was associated with significantly poorer performance on shifting (g = 0.32) and updating (g = 0.11). Positive schizotypy was associated with significantly poorer performance on shifting (g = 0.18). There were no significant associations between schizotypy and inhibition. The divergence in results for positive, negative, and disorganized schizotypy emphasizes the importance of examining relationships between cognition and the facets of schizotypy rather than using the overall score. Our findings also underline the importance of more detailed research to further understand and define this complex personality construct, which will also be of importance when applying schizotypy as a model system for psychosis.

Effects of lorazepam on saccadic eye movements: the role of sex, task characteristics and baseline traits.

BACKGROUND: Saccadic eye movements are controlled by a network of parietal, frontal, striatal, cerebellar and brainstem regions. The saccadic peak velocity is an established biomarker of benzodiazepine effects, with benzodiazepines reliably reducing the peak velocity. AIMS: In this study, we aimed to replicate the effects of benzodiazepines on peak velocity and we investigated effects on previously less studied measures of saccades. We also explored the roles of sex, task characteristics and the baseline variables age, intelligence and trait anxiety in these effects. METHOD: Healthy adults ( N = 34) performed a horizontal step prosaccade task under 1 mg lorazepam, 2 mg lorazepam and placebo in a double-blind, within-subjects design. RESULTS: We replicated the dose-dependent reduction in peak velocity with lorazepam and showed that this effect is stronger for saccades to targets at smaller eccentricities. We also demonstrated that this effect is independent of sex and other baseline variables. Lorazepam effects were widespread, however, occurring on mean and variability measures of most saccadic variables. Additionally, there were sex-dependent lorazepam effects on spatial consistency of saccades, indicating more adverse effects in females. CONCLUSIONS: We conclude that saccadic peak velocity is a sensitive and robust biomarker of benzodiazepine effects. However, lorazepam has pronounced effects also on other parameters of horizontal saccades. Sex-dependent drug effects on spatial consistency may reflect cerebellar mechanisms, given the role of the cerebellum in saccadic spatial accuracy.

Impaired Antisaccades in Obsessive-Compulsive Disorder: Evidence From Meta-Analysis and a Large Empirical Study.

Increasing evidence indicates that patients with obsessive-compulsive disorder (OCD) exhibit alterations in fronto-striatal circuitry. Performance deficits in the antisaccade task would support this model, but results from previous small-scale studies have been inconclusive as either increased error rates, prolonged antisaccade latencies, both or neither have been reported in OCD patients. In order to address this issue, we investigated antisaccade performance in a large sample of OCD patients (n = 169) and matched control subjects (n = 183). As impaired antisaccade performance constitutes a potential endophenotype of OCD, unaffected first-degree relatives of OCD patients (n = 100) were assessed, as well. Furthermore, we conducted a quantitative meta-analysis to integrate our data with previous findings. In the empirical study, OCD patients exhibited significantly increased antisaccade latencies, intra-subject variability (ISV) of antisaccade latencies, and antisaccade error rates. The latter effect was driven by errors with express latency (80-130 ms), as patients did not differ significantly from controls with regards to regular errors (>130 ms). Notably, unaffected relatives of OCD patients showed elevated antisaccade express error rates and increased ISV of antisaccade latencies, as well. Antisaccade performance was not associated with state anxiety within groups. Among relatives, however, we observed a significant correlation between antisaccade error rate and harm avoidance. Medication status of OCD patients, symptom severity, depressive comorbidity, comorbid anxiety disorders and OCD symptom dimensions did not significantly affect antisaccade performance. Meta-analysis of 10 previous and the present empirical study yielded a medium-sized effect (SMD = 0.48, p < 0.001) for higher error rates in OCD patients, while the effect for latencies did not reach significance owing to strong heterogeneity (SMD = 0.51, p = 0.069). Our results support the assumption of impaired antisaccade performance in OCD, although effects sizes were only moderately large. Furthermore, we provide the first evidence that increased antisaccade express error rates and ISV of antisaccade latencies may constitute endophenotypes of OCD. Findings regarding these more detailed antisaccade parameters point to potentially underlying mechanisms, such as early pre-stimulus inhibition of the superior colliculus.