Search

Deficits in metacognition, the ability to monitor one's own mental states, are key elements of the functional pathology of schizophrenia spectrum disorders. Little is known, however, about the integrity of metacognitive processes in subclinical schizotypy. The purpose of the present investigation was two-fold: First, we conducted a preregistered, systematic literature review to synthesize previous research efforts on the role of metacognition in schizotypy. Second, we investigated the relationship between self-reported dimensions of schizotypy and psychometric as well as behavioral measures of metacognition in a preregistered online study. A large sample (N = 330) completed a questionnaire battery and an episodic memory experiment; task-based metacognition was tapped via trial-by-trial confidence ratings. In keeping with findings from our literature review, higher schizotypy was associated with diminished introspective insight and an overly self-referential and maladaptive metacognitive style in metacognition questionnaires. Importantly, low task-based metacognitive efficiency was predictive of high levels of cognitive disorganization, whereas task-related overconfidence (i.e., increased metacognitive bias) was linked with positive schizotypy. Due to the comparatively small number of k = 20 studies meeting our inclusion criteria, the systematic literature review provides only preliminary indications for potential conclusions. Furthermore, control over potential disturbing influences in the experimental study was limited due to its online format. Overall, we provide evidence for specific metacognitive deficits in schizotypy and discuss a potential continuity of preserved and impaired aspects of metacognitive monitoring along the psychosis continuum. • We investigated the role of metacognitive processes in subclinical schizotypy. • We combined a systematic literature review with an experimental study. • Schizotypy was associated with less clarity of insight and a self-referential style. • Behaviorally assessed metacognitive efficiency predicted cognitive disorganization. [ABSTRACT FROM AUTHOR]

Background: Schizotypy, a putative schizophrenia endophenotype, has been associated with brain-structural variations partly overlapping with those in psychotic disorders. Variations in precuneus structure have been repeatedly reported, whereas the involvement of fronto-striatal networks – as in schizophrenia – is less clear. While shared genetic architecture is thought to increase vulnerability to environmental insults, beneficial factors like general intelligence might buffer their effect. Methods: To further investigate the role of fronto-striatal networks in schizotypy, we examined the relationship of voxel- and surface-based brain morphometry and a measure of schizotypal traits (Schizotypal Personality Questionnaire, with subscores Cognitive-Perceptual, Interpersonal, Disorganised) in 115 healthy participants [54 female, mean age (s.d.) = 27.57(8.02)]. We tested intelligence (MWT-B) as a potential moderator. Results: We found a positive association of SPQ Cognitive-Perceptual with putamen volume (p = 0.040, FWE peak level-corrected), moderated by intelligence: with increasing IQ, the correlation of SPQ Cognitive-Perceptual and striatal volume decreased (p = 0.022). SPQ Disorganised was positively correlated with precentral volume (p = 0.013, FWE peak level-corrected). In an exploratory analysis (p < 0.001, uncorrected), SPQ total score was positively associated with gyrification in the precuneus and postcentral gyrus, and SPQ Disorganised was negatively associated with gyrification in the inferior frontal gyrus. Conclusions: Our findings support the role of fronto-striatal networks for schizotypal features in healthy individuals, and suggest that these are influenced by buffering factors like intelligence. We conclude that protective factors, like general cognitive capacity, might attenuate the psychosis risk associated with schizotypy. These results endorse the idea of a continuous nature of schizotypy, mirroring similar findings in schizophrenia. [ABSTRACT FROM AUTHOR]

Gray's theory of personality postulates that fear and anxiety are distinct emotional systems with only the latter being sensitive to anxiolytic drugs. His work was mainly based on animal research, and translational studies validating his theory are scarce. Previous work in humans showed an influence of the benzodiazepine lorazepam on both systems, however, dependent on dosage (1 and 2 mg) and personality differences in negative emotionality. The present study aims to replicate these findings, and in addition tests the drug threshold effect by introducing a lower dosage of 0.5 mg lorazepam. Fifty healthy adults (23 males, agemean 22.40, SD ± 3.68) participated in an experimental threat-avoidance paradigm designed to dissociate risk assessment intensity (RAI, reflecting anxiety) and flight intensity (FI, reflecting fear) and completed two self-report questionnaires assessing facets of negative emotionality (Spielberger State Trait Anxiety Inventory and Fear Survey Schedule). In a randomized placebo-controlled within-subjects design, 0.5 and 1 mg of lorazepam were applied per os. Saccadic peak velocity was assessed by means of eye-tracking in order to control for sedating drug effects. Results showed the expected and specific anxiolytic effect of lorazepam on RAI, however, only in the 0.5 mg condition. FI was not influenced by lorazepam, and previous findings of interaction effects of lorazepam with self-reported negative emotionality could not be corroborated. Overall, this study demonstrates anxiolytic effects of lorazepam in dosages ≤1 mg in the absence of a drug effect on fear using a translational behavioural task. However, a putative moderating role of personality on defensive behaviour has to be clarified in future research. [ABSTRACT FROM AUTHOR]

In recent years there has been a surge of interest and corresponding accumulation of knowledge about the role of sleep disturbance in schizophrenia. In this review, we provide an update on the current status of experimentally controlled sleep deprivation (SD) as an experimental medicine model of psychosis, and also consider, given the complexity and heterogeneity of schizophrenia, whether this (state) model can be usefully combined with other state or trait model systems to more powerfully model the pathophysiology of psychosis. We present evidence of dose-dependent aberrations that qualitatively resemble positive, negative and cognitive symptoms of schizophrenia as well as deficits in a range of translational biomarkers for schizophrenia, including prepulse inhibition, smooth pursuit and antisaccades, following experimentally controlled SD, relative to standard sleep, in healthy volunteers. Studies examining the combination of SD and schizotypy, a trait model of schizophrenia, revealed only occasional, task-dependent superiority of the combination model, relative to either of the two models alone. Overall, we argue that experimentally controlled SD is a valuable experimental medicine model of schizophrenia to advance our understanding of the pathophysiology of the clinical disorder and discovery of more effective or novel treatments. Future studies are needed to test its utility in combination with other, especially state, model systems of psychosis such as ketamine. [ABSTRACT FROM AUTHOR]

While impairments in executive functions have been well established in major depressive disorder (MDD), specific deficits in proactive control have scarcely been studied so far. Proactive control refers to cognitive processes during anticipation of a behaviorally relevant event that facilitate readiness to react. In this study, cerebral blood flow responses were investigated in MDD patients during a precued antisaccade task requiring preparatory attention and proactive inhibition. Using functional transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 40 MDD patients and 40 healthy controls. In the task, a target appeared left or right of the fixation point 5 s after a cuing stimulus; subjects had to move their gaze to the target (prosaccade) or its mirror image position (antisaccade). Video-based eye-tracking was applied for ocular recording. A right dominant blood flow increase arose during prosaccade and antisaccade preparation, which was smaller in MDD patients than controls. Patients exhibited a higher error rate than controls for antisaccades but not prosaccades. The smaller blood flow response may reflect blunted anticipatory activation of the dorsolateral prefrontal and inferior parietal cortices in MDD. The patients' increased antisaccade error rate suggests deficient inhibitory control. The findings support the notion of impairments in proactive control in MDD, which are clinically relevant as they may contribute to the deficits in cognition and behavioral regulation that characterize the disorder. [ABSTRACT FROM AUTHOR]

The ability to inhibit inappropriate responses and suppress irrelevant information is a core feature of executive control. In this study, we provide a detailed analysis of prepotent response inhibition and interference in patients with schizophrenia. To further test the role of genetic factors and subclinical schizophrenia‐like traits, we additionally studied clinically unaffected, first‐degree relatives of schizophrenia patients and assessed dimensions of schizotypy in both relatives and healthy controls. Inhibition and interference control were assessed using a battery comprising the antisaccade, Stroop, stop signal, go/no‐go, flanker, and Simon tasks. Schizophrenia patients differed from both relatives and controls in making more errors on the antisaccade task and having longer response times on the Stroop task, especially the incongruent condition. Patients also had general, that is, condition independent, increases in reaction times on the go/no‐go and flanker tasks and made more errors on the flanker and Simon tasks, suggesting general performance impairments independent of inhibitory demand. Relatives were characterized by hypometric antisaccade amplitude gain despite normal prosaccades, suggesting a selective deficit in non‐standard sensorimotor transformations. Schizotypy was correlated with inhibitory performance across a number of tasks in both relatives and controls. Generally, these effects were independent of verbal intelligence levels. Overall, the findings point to rather selective impairments of inhibitory control in the schizophrenia spectrum and confirm a previously observed deficit in antisaccade spatial accuracy as an endophenotype of schizophrenia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Executive functions (EFs) comprise the updating, shifting and inhibition dimensions. According to the Unity and Diversity Model, the inhibition dimension is fully accounted for by a general EFs factor. This suggests that training of inhibition should transfer, in part, to updating and shifting. Therefore, we tested the effectiveness of a three-week inhibition training (high-conflict Stroop task) and explored near transfer effects to an untrained inhibition task (antisaccade task) and far transfer effects to untrained tasks demanding task-set shifting (number-letter-task), working memory updating (n-back task) and planning abilities (Stockings of Cambridge task). We employed a randomized pretest/treatment/posttest study design in n = 102 healthy young adults, assigned to an intensive Stroop training (n = 38), an active control condition (n = 34) or no training intervention (n = 30). In the Stroop training group, Stroop performance improved with practice, while performance in the active control group remained unchanged. The Stroop training group showed improvements in overall Stroop task performance from pretest to posttest, but we observed neither near nor far transfer effects. Additionally, specifically stronger gains on incongruent Stroop trials compared to congruent trials were observed in the Stroop training group when color bar trials were excluded from the pretest-posttest-analysis. Generally, there were substantial improvements from pretest to posttest independent of training condition in all transfer tasks. In sum, our data do not support the existence of transfer effects from inhibition training in healthy young adults. [ABSTRACT FROM AUTHOR]

Altered striatocortical functional connectivity has been suggested to be a trait marker of schizophrenia spectrum disorders, including schizotypal personality. In the present study, we examined the association between schizotypal personality traits and striatocortical functional connectivity in a sample of healthy adults. The German version of the Schizotypal Personality Questionnaire was obtained from N = 111 participants recruited from the general public. Resting-state functional magnetic resonance imaging scans were acquired at 3T. Six striatal seed regions in each hemisphere were defined and striatocortical resting-state functional connectivity (rsFC) as well as its lateralization indices was calculated. Regression analysis showed that schizotypy scores, especially from the positive dimension, were positively correlated with rsFC between ventral striatum and frontal cortex and negatively associated with rsFC between dorsal striatum and posterior cingulate. No significant associations were found between negative dimension schizotypy and striatocortical rsFC. We also found positive correlations between schizotypy total scores and lateralization index of right dorsal caudate and right rostral putamen. In conclusion, the present study extends previous evidence of altered striatocortical rsFC in the schizophrenia spectrum. The observed associations resemble in part the alterations observed in psychotic patients and their relatives, providing support for dimensionality from schizotypal personality to the clinical disorder. Hum Brain Mapp 39:288-299, 2018. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We developed a cued pro- and antisaccade paradigm (CPAP) to explore automatic components of sexual interest. Heterosexual participants (n = 32 women, n = 25 men) had to perform fast eye movements toward and away from sexually relevant or irrelevant stimuli across a congruent (i.e., prosaccade toward sexually relevant stimuli, antisaccade away from sexually irrelevant stimuli) and an incongruent condition (i.e., prosaccade toward sexually irrelevant stimuli, antisaccade away from sexually relevant stimuli). We hypothesized that pro- and antisaccade performance would be influenced by the sexual interest-specific relevance of the presented stimulus (i.e., nude female or male stimulus) and the instructed task (i.e., pro- or antisaccade) and, thus, differ meaningfully between conditions. Results for prosaccades toward sexually relevant stimuli in the congruent condition showed that error rates were lower and latencies were shorter compared with prosaccades toward sexually irrelevant stimuli in the incongruent condition, but only for male participants. In addition, error rates for antisaccades away from sexually irrelevant stimuli in the congruent condition were lower than for antisaccades away from sexually relevant stimuli in the incongruent condition, for both female and male participants. Latencies of antisaccades, however, did not differ between conditions. In comparison with established indirect sexual interest paradigms, the CPAP benefits from measuring highly automated processes less prone to deliberate control. To this end, the CPAP could be applied to explore the interplay of early automatic and deliberate components of sexual information processing. [ABSTRACT FROM AUTHOR]

Executive function impairments have been frequently observed in depressive disorders. Moreover, reduced heart rate variability (HRV) has repeatedly been described, especially in the high frequency band (i.e., respiratory sinus arrhythmia, RSA), suggesting lower vagal cardiac outflow. The study tested the hypothesis of involvement of low vagal tone in executive dysfunction in depression. In addition to RSA, HRV in the low frequency (LF) band was assessed. In 36 patients with depression and 36 healthy subjects, electrocardiography recordings were accomplished at rest and during performance of five executive function tasks (number-letter task, n-back task, continuous performance test, flanker task, and antisaccade task). Patients displayed increased error rates and longer reaction times in the task-switching condition of the number-letter task, in addition to increased error rates in the n-back task and the final of two blocks of the antisaccade task. In patients, both HRV parameters were lower during all experimental phases. RSA correlated negatively with reaction time during task-switching. This finding confirms reduced performance across different executive functions in depression and suggests that, in addition to RSA, LF HRV is also diminished. However, the hypothesis of involvement of low parasympathetic tone in executive dysfunction related to depression received only limited support. [ABSTRACT FROM AUTHOR]

Nicotine is a cholinergic agonist with known pro-cognitive effects in the domains of alerting and orienting attention. However, its effects on attentional top-down functions such as response inhibition and interference control are less well characterised. Here, we investigated the effects of 7 mg transdermal nicotine on performance on a battery of response inhibition and interference control tasks. A sample of N = 44 healthy adult non-smokers performed antisaccade, stop signal, Stroop, go/no-go, flanker, shape matching and Simon tasks, as well as the attentional network test (ANT) and a continuous performance task (CPT). Nicotine was administered in a within-subjects, double-blind, placebo-controlled design, with order of drug administration counterbalanced. Relative to placebo, nicotine led to significantly shorter reaction times on a prosaccade task and on CPT hits but did not significantly improve inhibitory or interference control performance on any task. Instead, nicotine had a negative influence in increasing the interference effect on the Simon task. Nicotine did not alter inter-individual associations between reaction times on congruent trials and error rates on incongruent trials on any task. Finally, there were effects involving order of drug administration, suggesting practice effects but also beneficial nicotine effects when the compound was administered first. Overall, our findings support previous studies showing positive effects of nicotine on basic attentional functions but do not provide direct evidence for an improvement of top-down cognitive control through acute administration of nicotine at this dose in healthy non-smokers. [ABSTRACT FROM AUTHOR]

The gene coding for the dopamine transporter (DAT), SLC6A3 , contains a 40-base pair variable number of tandem repeats (VNTR) polymorphism (rs28363170) in its 3′ untranslated region. This VNTR has been associated with attention deficit hyperactivity disorder (ADHD) and has been investigated in relation to cognition and brain function. Here, we report the results of a comprehensive meta-analysis with meta-regression examining the association of the VNTR with different domains of cognition in healthy adults. We extracted data from 28 independent studies and carried out meta-analyses for associations with working memory ( k = 10 samples, N = 1193 subjects), inhibition ( k = 8 samples, N = 829 subjects), executive functions including inhibition ( k = 10 samples, N = 984 subjects), attention ( k = 6 samples, N = 742 subjects) and declarative long-term memory ( k = 5 samples, N = 251 subjects). None of the investigated dimensions showed significant associations with the VNTR (all p > 0.26). Meta-regression including year of publication, gender, age, ethnicity and percentage of 10R-homozygotes similarly did not attain significance. We conclude that there is no evidence that rs28363170 may be a significant predictor of cognitive function in healthy adults. [ABSTRACT FROM AUTHOR]

Rationale: Most cognitive domains show only minimal improvement following typical or atypical antipsychotic treatments in schizophrenia, and some may even worsen. One domain that may worsen is procedural learning, an implicit memory function relying mainly on the integrity of the fronto-striatal system. Objectives: We investigated whether switching to atypical antipsychotics would improve procedural learning and task-related neural activation in patients on typical antipsychotics. Furthermore, we explored the differential effects of the atypical antipsychotics risperidone and olanzapine. Methods: Thirty schizophrenia patients underwent functional magnetic resonance imaging during a 5-min procedural (sequence) learning task on two occasions: at baseline and 7-8 weeks later. Of 30 patients, 10 remained on typical antipsychotics, and 20 were switched randomly in equal numbers to receive either olanzapine (10-20 mg) or risperidone (4-8 mg) for 7-8 weeks. Results: At baseline, patients (all on typical antipsychotics) showed no procedural learning. At follow-up, patients who remained on typical antipsychotics continued to show a lack of procedural learning, whereas those switched to atypical antipsychotics displayed significant procedural learning ( p = 0.001) and increased activation in the superior-middle frontal gyrus, anterior cingulate and striatum (cluster-corrected p < 0.05). These neural effects were present as a linear increase over five successive 30-s blocks of sequenced trials. A switch to either risperidone or olanzapine resulted in comparable performance but with both overlapping and distinct task-related activations. Conclusions: Atypical antipsychotics restore procedural learning deficits and associated neural activity in schizophrenia. Furthermore, different atypical antipsychotics produce idiosyncratic task-related neural activations, and this specificity may contribute to their differential long-term clinical profiles. [ABSTRACT FROM AUTHOR]

The pineal gland (PG) is a small interhemispheric brain structure that influences human physiology in many ways, most importantly via secretion of the hormone melatonin which is known to regulate sleep and wakefulness. Here, we systematically reviewed existing neuroimaging studies of PG structure, and/or melatonin release (MLT) in psychosis and mood disorders. Medline, PubMed, and Web of Science databases were searched (on 3 February 2023), yielding 36 studies (8 PG volume, 24 MLT). The findings showed smaller-than-normal PG volume in people with schizophrenia, regardless of symptom severity and illness stage; and smaller-than-normal PG volume in major depression, with some indication of this being present only in certain subgroups, or in those with high scores on the 'loss of interest' symptom. There was considerable evidence of lower-than-normal MLT as well as aberrant MLT secretion pattern in schizophrenia. A similar picture, though less consistent than that seen in schizophrenia, emerged in major depression and bipolar disorder, with some evidence of a transient lowering of MLT following the initiation of certain antidepressants in drug-withdrawn patients. Overall, PG and MLT aberrations appear to represent transdiagnostic biomarkers for psychosis and mood disorders, but further work is needed to establish their clinical correlates and treatment implications. [ABSTRACT FROM AUTHOR]

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 variancewas again trait determined. Trait changeswere 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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Large-scale study on relations between the Short UPPS-P and temporal discounting. • Impulsigenic traits are weakly yet significantly related to temporal discounting. • The data do not support the separation of Positive and Negative Urgency. • Lack of Premeditation appears to be central to impulsive personality. Impulsivity is an ill-defined umbrella term. Therefore, in addition to factor-analytic models, network models that characterize the relative positions of their components can offer novel insights. Here, we investigated the structure of impulsivity in 1000 participants using the Short UPPS-P Impulsive Behavior Scale and a temporal discounting task. Our results revealed an acceptable fit of a five-factor solution of the Short UPPS-P but question the separability of Positive and Negative Urgency. Additionally, Lack of Premeditation showed high closeness centrality and was – like Positive and Negative Urgency – significantly yet weakly related to temporal discounting. It remains to be investigated further to what extent Lack of Premeditation is a common cause or consequence of other impulsivity components. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rationale: Prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating, can be enhanced by nicotine. Moreover, the TT genotype of the nicotinic acetylcholine receptor (nAChR) α3-subunit ( CHRNA3) rs1051730 polymorphism has previously been associated with diminished PPI and nicotine dependence. Objectives: We tested whether this CHRNA3 polymorphism also modulates the nicotine-induced enhancement of PPI. Methods: We assessed the effect of nicotine on PPI, startle reactivity, and habituation in 52 healthy nonsmoking volunteers genotyped for CHRNA3 rs1051730 in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Additionally, cotinine plasma levels were measured. Results: Nicotine significantly enhanced PPI in TT homozygotes only and tended to worsen PPI in TC and CC carriers. Additionally, nicotine significantly reduced startle habituation. Conclusions: The present findings imply that the effect of nicotine on sensorimotor gating is modulated by nAChR α3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior. [ABSTRACT FROM AUTHOR]

Abstract: Detailed measurements of saccadic latency – the time taken to make an eye movement to a suddenly-presented visual target – have proved a valuable source of detailed and quantitative information in a wide range of neurological conditions, as well as shedding light on the mechanisms of decision, currently of intense interest to cognitive neuroscientists. However, there is no doubt that more complex oculomotor tasks, and in particular the antisaccade task in which a participant must make a saccade in the opposite direction to the target, are potentially more sensitive indicators of neurological dysfunction, particularly in neurodegenerative conditions. But two obstacles currently hinder their widespread adoption for this purpose. First, that much of the potential information from antisaccade experiments, notably about latency distribution and amplitude, is typically thrown away. Second, that there is no standardised protocol for carrying out antisaccade experiments, so that results from one laboratory cannot easily be compared with those from another. This paper, the outcome of a recent international meeting of oculomotor scientists and clinicians with an unusually wide experience of such measurements, sets out a proposed protocol for clinical antisaccade trials: its adoption will greatly enhance the clinical and scientific benefits of making these kinds of measurements. [Copyright &y& Elsevier]

Eye movements are sensitive indicators of pharmacological effects on sensorimotor and cognitive processing. Methylphenidate (MPH) is one of the most prescribed medications in psychiatry. It is increasingly used as a cognitive enhancer by healthy individuals. However, little is known of its effect on healthy cognition. Here we used oculomotor tests to evaluate the effects of MPH on basic oculomotor and executive functions. Twenty-nine males were given 20mg of MPH orally in a double-blind placebo-controlled crossover design. Participants performed visually-guided saccades, sinusoidal smooth pursuit, predictive saccades and antisaccades one hour post-capsule administration. Heart rate and blood pressure were assessed prior to capsule administration, and again before and after task performance. Visually-guided saccade latency decreased with MPH (p<0.004). Smooth pursuit gain increased on MPH (p<0.001) and number of saccades during pursuit decreased (p<0.001). Proportion of predictive saccades increased on MPH (p<0.004), specifically in conditions with predictable timing. Peak velocity of predictive saccades increased with MPH (p<0.01). Antisaccade errors and latency were unaffected. Physiological variables were also unaffected. The effects on visually-guided saccade latency and peak velocity are consistent with MPH effects on dopamine in basal ganglia. The improvements in predictive saccade conditions and smooth pursuit suggest effects on timing functions. [ABSTRACT FROM AUTHOR]

Objectives. Schizophrenia is associated with replicable grey matter volume reductions in fronto-temporo-limbic and subcortical regions. Psychometric schizotypy refers to a set of behavioural traits and cognitions thought to represent the subclinical manifestation of schizophrenia in the general population. While there is evidence of a continuum between schizophrenia and schizotypy at phenotypic, genetic and cognitive levels, no previous study has observed grey matter volume reductions associated with increased psychometric schizotypy levels in healthy individuals. Such evidence would provide further support for a relationship between non-clinical schizophrenia-like traits in the general population and the full-blown clinical condition of schizophrenia. Methods. We used magnetic resonance imaging to investigate the relationship between psychometric schizotypy and brain structure in 55 clinically unaffected and unmedicated volunteers. We performed a voxel-based morphometry analysis of grey matter volume data obtained at 1.5 Tesla. Results. Covarying for age and gender, higher scores of self-report positive schizotypy were significantly associated with reduced grey matter volume in medial prefrontal, orbitofrontal, and temporal cortical regions. Conclusions. These findings show that psychometric schizotypy in healthy individuals is associated with volume reductions in cortical areas known to be altered in schizophrenia, thereby providing neurobiological evidence of a continuum between schizotypy and schizophrenia. [ABSTRACT FROM AUTHOR]

Mean pupil size during fixation has been suggested to reflect interindividual differences in working memory and fluid intelligence. However, due to small samples with limited age range (17–35 years) and suboptimal light conditions in previous studies, these associations are still controversial and it is unclear whether they are observed at older ages. Therefore, we assessed whether interindividual differences in cognitive performance are reflected in pupil diameter during fixation and whether these associations are age‐dependent. We analyzed pupillometry and cognition data of 4560 individuals aged 30–95 years of the community‐based Rhineland Study. Pupillometry data were extracted from a one‐minute fixation task. The cognitive test battery included tests of oculomotor control, working memory, episodic verbal memory, processing speed, executive function, and crystallized intelligence. For data analysis, we used multivariable regression models. Working memory and global cognition were not associated with pupil diameter during fixation. Better processing speed performance was associated with larger pupil diameter during fixation. Associations between cognition and pupil diameter during fixation hardly varied with age, but pupil diameter during fixation declined linearly with age (adjusted decline: 0.33 mm per 10 years of age). There were no significant sex differences in pupil size. We conclude that interindividual differences in mean pupil diameter during fixation may partly reflect interindividual differences in the speed of processing and response generation. We could not confirm that interindividual differences in working memory and fluid intelligence are reflected in pupil size during fixation; however, our sample differed in age range from previous studies. Our study contributes to the intense debate on whether or not interindividual differences in working memory capacity and fluid intelligence are reflected in mean pupil size during fixation. In our large dataset of 4560 participants aged 30 to 95 years, we could not confirm that mean pupil size during fixation reflects interindividual differences in working memory capacity or fluid intelligence. However, our findings suggest that mean pupil diameter during fixation may inform about interindividual differences in levels of preparatory neural activity for motor responses. [ABSTRACT FROM AUTHOR]

Rationale: Nicotinergic agents are currently examined as possible pro-cognitive drugs for a variety of clinical conditions marked by cognitive deficits, such as attention deficit hyperactivity disorder (ADHD) or schizophrenia. The response to acute nicotine is heterogeneous across subjects and samples; however, only a few reliable predictors of response have been identified. Objectives: We tested the hypothesis that baseline performance level in cognitive control may be a predictor of the cognitive effects of nicotine. Methods: We tested 28 healthy Caucasian, male, non-smoking volunteers with the antisaccade task, an oculomotor measure of cognitive control. Participants were given a 7-mg nicotine patch in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Subjects were stratified into high and low performers based on their antisaccade error rate in the placebo condition (median split). Results: Nicotine tended to reduce response time variability of prosaccade latency ( p = 0.06). There was no main effect of nicotine on antisaccade error rate ( p = 0.31). However, nicotine significantly reduced antisaccade error rate in the low-accuracy probands while leaving performance of the high-accuracy probands unaffected (interaction, p < 0.05). Furthermore, we found a nicotine-induced reduction of response time variability of antisaccade latency at one target location in the low-performing group (interaction, p < 0.05). Conclusions: The present results demonstrate the importance of baseline performance differences for the effectiveness of pharmacological enhancement of cognitive control. More generally, the results suggest that stimulation of the nicotinic acetylcholine receptor system might be an effective way of improving cognition in people with poor cognitive performance, such as patients with ADHD or schizophrenia. [ABSTRACT FROM AUTHOR]

A fear of being rejected can cause perceptions of more insecurity and stress in close relationships. Healthy individuals activate the dorsal anterior cingulate cortex (dACC) when experiencing social rejection, while those who are vulnerable to depression deactivate the dACC presumably to downregulate salience of rejection cues and minimize distress. Schizotypal individuals, characterized by unusual perceptual experiences and/or odd beliefs, are more rejection sensitive than normal. We tested the hypothesis, for the first time, that individuals with high schizotypy also have an altered dACC response to rejection stimuli. Twenty-six healthy individuals, 14 with low schizotypy (LS) and 12 with high schizotypy (HS), viewed depictions of rejection and acceptance and neutral scenes while undergoing functional MRI. Activation maps in LS and HS groups during each image type were compared using SPM5, and their relation to participant mood and subjective ratings of the images was examined. During rejection relative to neutral scenes, LS activated and HS deactivated the bilateral dACC, right superior frontal gyrus, and left ventral prefrontal cortex. Across both groups, a temporo-occipito-parieto-cerebellar network was active during rejection, and a left fronto-parietal network during acceptance, relative to neutral scenes, and the bilateral lingual gyrus during rejection relative to acceptance scenes. Our finding of dACC-dorso-ventral PFC activation in LS, but deactivation in HS individuals when perceiving social rejection scenes suggests that HS individuals attach less salience to and distance themselves from such stimuli. This may enable them to cope with their higher-than-normal sensitivity to rejection. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Rationale: Working memory dysfunction is frequently observed in schizophrenia. The neural mechanisms underlying this dysfunction remain unclear, with functional neuroimaging studies reporting increased, decreased or unchanged activation compared to controls. Objectives: We investigated the neural correlates of spatial working memory in schizophrenia with particular consideration of effects of antipsychotic treatment and relation to performance levels in the patient group. Method: We used functional magnetic resonance imaging and studied the blood-oxygen-level-dependent (BOLD) response of 45 schizophrenia outpatients and 19 healthy controls during a parametric spatial n-back task. Results: Performance in both groups deteriorated with increasing memory load (0-back, 1-back, 2-back), but the two groups did not significantly differ in performance overall or as a function of load. Patients produced stronger BOLD signal in occipital and lateral prefrontal cortex during task performance than controls. This difference increased with increasing working memory load in the prefrontal areas. We also found that in patients with good task performance, the BOLD response in left prefrontal cortex showed a stronger parametric increase with working memory load than in patients with poor performance. Second-generation antipsychotics were independently associated with left prefrontal BOLD increase in response to working memory load, whereas first-generation antipsychotics were associated with BOLD decrease with increasing load in this area. Conclusions: Together, these findings suggest that in schizophrenia patients, normal working memory task performance may be achieved through compensatory neural activity, especially in well-performing patients and in those treated with second-generation antipsychotics. [ABSTRACT FROM AUTHOR]

In a large-scale meta-analysis, it has been recently shown that the transcription factor 4 (TCF4) gene is among the most prominent susceptibility genes for schizophrenia. Moreover, transgenic mice overexpressing TCF4 in the brain display a reduction of sensorimotor gating measured by prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI is heritable and has been established as an important translational endophenotype of schizophrenia. We therefore investigated the impact of the schizophrenia susceptibility gene TCF4 (rs9960767) on sensorimotor gating of the ASR in healthy humans and in patients with a schizophrenia spectrum disorder. We assessed PPI, startle reactivity, and habituation of the ASR in two independent samples. The first sample consisted of 107 healthy volunteers from London, UK. The second sample was a schizophrenia spectrum group (n = 113) of 73 schizophrenia patients and 40 individuals at high risk for schizophrenia from Bonn, Germany (total sample n=220). In both samples, PPI was strongly decreased in carriers of the schizophrenia risk allele C of the TCF4 gene (meta-analysis across both samples: p=0.00002), whereas startle reactivity and habituation were unaffected by TCF4 genotype. Sensorimotor gating is modulated by TCF4 genotype, indicating an influential role of TCF4 gene variations in the development of early information-processing deficits in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: There is strong evidence for significant contributions of genetic factors to the risk of schizophrenia. In the past 10 years, studies employing linkage and association approaches have identified multiple putative schizophrenia risk genes. For most of these, the evidence for association with schizophrenia remains weak and attempts of replication not always successful nor easy to interpret. Aim: To give an overview of new developments in genetic research of schizophrenia. Methods: The present literature on schizophrenia genetics was reviewed with special emphasis on new developments such as genome-wide association studies (GWAS), associations of copy number variations (CNVs) with schizophrenia and the role of endophenotypes in genetic research. Results: The first GWAS of schizophrenia have identified new putative candidate risk genes and opened avenues for investigating how multiple genes may act in functional biological pathways forming the genetic basis of schizophrenia and other complex diseases. There is growing evidence that rare de novo CNVs as well as some inherited CNVs contribute to the susceptibility to several neuropsychiatric disorders including schizophrenia. Schizophrenia endophenotypes, which possibly better represent biological phenomena than the complex clinical phenotype, are turning out to be helpful for investigating neurobiological pathways of putative risk genes. Conclusions: Recent studies suggest that individual common gene variants make relatively small contributions to risk of schizophrenia but some rare CNVs may be associated with much higher risk when present. Future studies employing new technologies for identifying common and rare risk markers are likely to deepen our understanding of the genetic architecture of schizophrenia. [ABSTRACT FROM AUTHOR]

It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition ( P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass ( r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Drugs that are clinically effective against generalized anxiety disorder preferentially alter rodent risk assessment behavior, whereas drugs that are clinically effective against panic disorder preferentially alter rodent flight behavior. The theoretical principle of "defensive direction" explains the pattern of associations between emotion and defensive behavior in terms of the differing functional demands arising from cautious approach to threat (anxiety) versus departure from threat (fear), offering the prospect that clinically important emotions may be explained using a single rubric of defense. We used a within-subjects, placebo-controlled, design to test this theory, measuring the effects of citalopram and lorazepam on the defensive behavior of 30 healthy adult male humans. We indexed human defensive behavior with a translation of an active avoidance task used to measure rodent defense and found that lorazepam significantly reduced the intensity of defensive behavior during approach to threat (hypothetically anxiety-related) but not departure from threat (hypothetically fear-related). Contrary to prediction, citalopram did not affect either form of defensive reaction. Since lorazepam is a drug with well established anxiety reducing properties, these data support the hypothesis that anxiety is an emotion elicited by threat stimuli that require approach. These data also contribute to the validation of a novel human analog of an established experimental model of rodent fear and anxiety. [ABSTRACT FROM AUTHOR]

Abstract: The present study used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms of nicotine effects on antisaccades (an oculomotor measure of the conflict between a reflexive response and a spatially complex volitional response) and prosaccades (involving reflexive overt attentional shifts). Given the known inter-individual variability in drug response we aimed to identify oculomotor variables and brain areas in which significant inter-individual heterogeneity in response to nicotine is observed. To do so we calculated within-session intraclass correlation (ICC) coefficients over measurements obtained before and after nicotine/placebo administration and reasoned that a significant reduction in ICC with nicotine compared to placebo would reflect the operation of significant inter-individual response heterogeneity. Thirteen light-to-moderate smokers and 11 non-smokers completed fMRI during antisaccades before and after subcutaneous injection of 12 μg/kg nicotine or saline placebo in a double-blind, randomised, cross-over design. All participants were healthy, right-handed males. Nicotine and placebo were given on separate occasions approximately 1 week apart with time of injection kept constant. Nicotine significantly reduced antisaccade latencies in both groups. At the level of brain function, during antisaccades the blood oxygen level dependent (BOLD) response in the left frontal eye field was non-significantly reduced by nicotine while it significantly increased following placebo in non-smokers, but there was no discernible effect in smokers. During prosaccades, it was found that deactivation areas (posterior cingulate gyrus and precuneus; right superior temporal gyrus) showed enhanced deactivations following nicotine administration in both groups. ICC analysis identified significant inter-individual response heterogeneity in antisaccade reflexive errors in smokers, and in a number of brain regions, particularly in non-smokers. These findings suggest that nicotine has beneficial effects at the cognitive level and leads to reductions in task-related activations and further decreases of BOLD in deactivation areas. The comparison of within-session ICCs across drug conditions suggests that the effects of nicotine are subject to inter-individual variability at behavioural and neural levels. [Copyright &y& Elsevier]

Abstract: Considerable research effort has focused on achieving a better understanding of the genetic correlates of individual differences in volumetric and morphological brain measures. The importance of these efforts is underlined by evidence suggesting that brain changes in a number of neuropsychiatric disorders are at least partly genetic in origin. The currently used methods to study these relationships are mostly based on single-genotype univariate analysis techniques. These methods are limited as multiple genes are likely to interact with each other in their influences on brain structure and function. In this paper we present a feasibility study where we show that by using kernel correlation analysis, with a new genotypes representation, it is possible to analyse the relative associations of several genetic polymorphisms with brain structure. The implementation of the method is demonstrated on genetic and structural magnetic resonance imaging (MRI) data acquired from a group of 16 healthy subjects by showing the multivariate genetic influence on grey and white matter. [Copyright &y& Elsevier]

Dehydration can affect brain structure which has important implications for human health. In this study, we measured regional changes in brain structure following acute dehydration. Healthy volunteers received a structural MRI scan before and after an intensive 90-min thermal-exercise dehydration protocol. We used two techniques to determine changes in brain structure: a manual point counting technique using MEASURE, and a fully automated voxelwise analysis using SIENA. After the exercise regime, participants lost (2.2% ± 0.5%) of their body mass. Using SIENA, we detected expansion of the ventricular system with the largest change occurring in the left lateral ventricle ( P = 0.001 corrected for multiple comparisons) but no change in total brain volume ( P = 0.13). Using manual point counting, we could not detect any change in ventricular or brain volume, but there was a significant correlation between loss in body mass and third ventricular volume increase ( r = 0.79, P = 0.03). These results show ventricular expansion occurs following acute dehydration, and suggest that automated longitudinal voxelwise analysis methods such as SIENA are more sensitive to regional changes in brain volume over time compared with a manual point counting technique. Hum Brain Mapp 2009. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The catechol-O-methyltransferase (COMT) val158met single nucleotide polymorphism (rs4680) has been shown to be associated with brain activation during a number of neurocognitive and emotional tasks. The present study evaluated genotypic associations with brain function during measurement of cognitive stability (prosaccades) and plasticity (antisaccades). A total of 36 healthy volunteers were genotyped for rs4680 and underwent functional magnetic resonance imaging (fMRI) at 1.5 T. Individuals with at least one val158 allele (val158 carriers, N=24) showed lower blood oxygen level-dependent (BOLD) response in ventromedial and dorsomedial prefrontal cortex during antisaccades compared to val158 noncarriers, whereas met158 homozygotes (N=12) showed lower BOLD response in a cluster in the posterior cingulate and precuneus during prosaccades compared to val158 carriers. These findings suggest that associations of COMT val158met genotype with brain function may be mediated by task characteristics. The findings may be compatible with a hypothesis on the role of COMT val158met genotype in tonic and phasic dopamine levels in brain and differential effects on cognitive measures of stability (eg prosaccades) and plasticity (eg antisaccades).Neuropsychopharmacology (2008) 33, 3046–3057; doi:10.1038/sj.npp.1301658; published online 30 January 2008 [ABSTRACT FROM AUTHOR]

Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes in genetic studies of schizophrenia. The Icelandic population lends itself ideally to genetic studies due to its ethnic homogeneity and well-documented genealogy. The primary aim of this study was to assess AS and SPEM performance in a large Icelandic sample. Additional aims were to investigate the relationship between AS and SPEM task performance and to assess internal consistency, within-session performance changes and effects of SPEM target velocity on performance. Patients with schizophrenia ( N = 118) and healthy controls ( N = 109) matched for age and gender underwent infrared oculographic assessment of AS and SPEM (at target velocities of 12°, 24° and 36°/s). On the AS task patients displayed significantly more reflexive errors, longer latency, increased intra-individual latency variability, and reduced amplitude gain compared to controls. On the SPEM task, patients had significantly lower velocity gain and more frequent saccades during pursuit at all velocities, but group differences in velocity gain increased with increasing target velocity. Internal consistency of performance was high for all variables in both groups (Cronbach’s alpha >0.77 for AS and >0.85 for SPEM) except for AS spatial error in patients (alpha = 0.38). A moderate association was found between AS and SPEM performance. By and large, patients and controls showed similar patterns of systematic within-session performance changes. Our findings confirm the existence of robust eye movement deficits in schizophrenia in a large sample. These measures may be studied as endophenotypes in future studies of potential schizophrenia risk genotypes in the genetically homogenous Icelandic population. [ABSTRACT FROM AUTHOR]

Previous research has suggested that there may be overlap between schizophrenia and attention-deficit hyperactivity disorder (ADHD). The relationship between schizotypal personality traits, ADHD features and polymorphisms was evaluated in dopamine-related genes. Thirty-one healthy, Caucasian men completed the Rust Inventory of Schizotypal Cognitions (RISC) and the ADHD Self-Report Scale (ASRS). Catechol-O-methyltransferase (COMT) Val158Met, dopamine receptors of the D3 type (DRD3) Ser9Gly, DRD4 variable number of tandem repeats (VNTR), and SLC6A3 VNTR polymorphisms were analyzed. RISC score was correlated with ASRS score ( r = 0.54, P = 0.003). COMT Met homozygotes had higher ASRS scores than Val homozygotes ( P = 0.005). These findings are consistent with evidence of overlap between schizophrenia and ADHD and support an involvement of COMT genotype in ADHD features. [ABSTRACT FROM AUTHOR]

The antisaccade task is a measure of volitional control of behavior sensitive to fronto-striatal dysfunction. Here we outline important issues concerning antisaccade methodology, consider recent evidence of the cognitive processes and neural mechanisms involved in task performance, and review how the task has been applied to study psychopathology. We conclude that the task yields reliable and sensitive measures of the processes involved in resolving the conflict between volitional and reflexive behavioral responses, a key cognitive deficit relevant to a number of neuropsychiatric conditions. Additionally, antisaccade deficits may reflect genetic liability for schizophrenia. Finally, the ease and accuracy with which the task can be administered, combined with its sensitivity to fronto-striatal dysfunction and the availability of suitable control conditions, may make it a useful benchmark tool for studies of potential cognitive enhancers. [ABSTRACT FROM AUTHOR]

Prepulse inhibition and the suppression of reflexive saccades on the antisaccade task are thought to tap inhibitory function. Reports of a lack of association between these measures suggest that they reflect different facets of inhibition. This study aimed to reexamine this relationship in a large sample and investigate the association of prepulse inhibition with oculomotor tasks that require inhibition of a reflexive saccade with lower concurrent processing demands than antisaccades, namely the oculomotor delayed response and fixation with distractors tasks. One hundred and seven healthy volunteers took part. Prepulse inhibition was uncorrelated with oculomotor performance. The error rate was highest for antisaccades, intermediate for the delayed response task, and lowest for fixation with distractors, and was correlated across tasks. These findings provide no evidence of a relationship between prepulse inhibition and oculomotor inhibition. Failure in suppressing reflexive saccades toward a peripheral target may represent a common inhibitory component underlying these oculomotor tasks. [ABSTRACT FROM AUTHOR]

Abstract: Individuals with schizophrenia, compared to healthy individuals, are known to exhibit deficient prepulse inhibition (PPI) of the startle response as well as reduced performance on the antisaccade task. There is evidence for genetic transmission of both PPI and antisaccadic abnormalities in schizophrenia. It has been suggested that PPI and antisaccade measures identify separate endophenotypes, on the basis of a lack of relationship between PPI and antisaccade deficits in patients with schizotypal personality disorder. However, given that patients with schizotypal personality disorder are unlikely to manifest all the abnormalities associated with schizophrenia, it is important to determine that there is no relationship present between these two abnormalities in people affected with schizophrenia. The main objective of this investigation therefore was to establish the lack of the association between PPI and antisaccade deficits in schizophrenia in two independent studies. Study 1 involved 39 patients with schizophrenia and 14 healthy controls and study 2 involved 35 patients with schizophrenia and 22 healthy controls. PPI (uninstructed paradigm) of the acoustically elicited startle (eye blink) was measured electromyographically. Antisaccadic eye movements (standard, non-overlap version) were measured using infrared oculography. Patients displayed reduced PPI and a lower percentage of correct antisaccades relative to healthy controls in both studies. As expected, no relationship occurred between PPI and the percentage of correct antisaccade responses in either group. It is concluded that PPI and antisaccade abnormalities in schizophrenia represent separate endophenotypes, reflecting the functions of different genetic aetiologies and different or only partially overlapping neural systems. [Copyright &y& Elsevier]

We previously reported that prosaccade amplitude gain and antisaccade error rate are correlated with cerebellar and posterior frontal grey matter volume, respectively. This study sought to replicate and extend these findings in a sample of 32 right-handed, healthy volunteers (14 males, 18 females). Participants underwent structural magnetic resonance imaging (MRI) at 1.5 T and an off-line eye movement assessment using infrared oculography at 500 Hz. Separate blocks of prosaccades and antisaccades were carried out (60 trials each). Optimised volumetric voxel-based morphometry (VBM) implemented in SPM99 was used to investigate the relationship of saccadic performance measures to regional grey matter volume, covarying for age. A significant negative correlation was obtained between prosaccade spatial error and grey matter volume in the right inferior cerebellar lobe (lobule VIIIB, extending into the vermis, centred at x = 11; y = −64; z = −61), indicating that more grey matter volume in this area was associated with better spatial accuracy. On the antisaccade task, the error rate was significantly negatively correlated with grey matter volume in the right middle frontal gyrus (Brodmann area 6) in an area anterior to the frontal eye field (centred at x = 27; y = 18; z = 50), indicating that more grey matter volume in this area was associated with fewer antisaccade errors. These findings extend our previous observations by identifying the relationship between brain structure and saccadic performance on a spatially highly localised scale and support the validity of structural neuroimaging methods in delineating the neural mechanisms underlying human oculomotor control. [Copyright &y& Elsevier]

We investigated the relationships of anti- and prosaccades with psychometric schizotypy. One aim was to estimate the role of negative emotionality and general psychopathology (i.e. neuroticism) in this relationship. 115 non-clinical volunteers underwent infrared oculographic assessment of antisaccades and prosaccades. Schizotypy was assessed with the Personality Syndrome Questionnaire (PSQ-80), the Rust Inventory of Schizotypal Cognitions (RISC), and Eysenck Personality Questionnaire-Revised (EPQ-R) Psychoticism. Higher positive schizotypy scores predicted increased antisaccade errors (RISC) and greater prosaccade spatial error (PSQ-80 Unreality). Greater thought disorder (PSQ-80 Activity) predicted shorter prosaccade latencies. EPQ-R Neuroticism was substantially correlated with schizotypy but was not related to saccadic measures and did not account for their relationship with schizotypy. We conclude that saccadic performance patterns in schizotypy are not due to negative emotionality or general psychopathology, but specific to schizophrenia spectrum signs and symptoms. [Copyright &y& Elsevier]

Objective: The authors investigated the structural brain correlates of antisaccade performance. Method: Magnetic resonance imaging was used to measure the volumes of the prefrontal, premotor, sensorimotor and occipitoparietal cortices as well as the caudate, thalamus, cerebellar vermis, and cerebrum in 20 first-episode Psychosis patients and 18 healthy comparison subjects, Antisaccades were recorded by using infrared oculography. Results: Groups significantly differed in terms of antisaccade error rate and amplitude gain and tended to differ in terms of latency but not brain region volumes. Premotor cortex volume predicted antisaccade error rate among comparison subjects, in the patient group, caudate volume was related to latency and amplitude gain, Negative symptoms, independent of structural volumes, predicted error rate. Conclusions: These findings point to altered structure-function relationships in first-episode psychosis. [ABSTRACT FROM AUTHOR]

Smooth pursuit eye movement (SPEM) and antisaccade deficits have been proposed as endophenotypes in the search for schizophrenia genes. We assessed these measures in 24 schizophrenia patients, 24 of their healthy siblings, and 24 healthy controls closely matched to the siblings. Between-group differences were assessed using a random effects regression model taking into account the relatedness between patients and siblings. Patients showed reduced SPEM gain, increased frequency of saccades during pursuit, increased antisaccade error rate, and reduced antisaccade gain compared to controls. Siblings performed intermediate, i.e. between patients and controls, on most measures, but were particularly characterised by reduced antisaccade gain. SPEM gain at one target velocity was significantly correlated between patients and siblings, highlighting the necessity of taking into account within-family correlations in the statistical analysis of between-group differences. It is concluded that subtle SPEM and antisaccade deficits are observed in clinically unaffected siblings of schizophrenia patients; these deficits may be useful markers of genetic liability to schizophrenia. [Copyright &y& Elsevier]

Smooth pursuit eye movement (SPEM) and antisaccade deficits are observed in the schizophrenia spectrum and have been used to study the pathophysiology as well as the genetic basis of this condition. The neurotransmitter acetylcholine has been implicated in a number of cognitive processes thought to underlie SPEM and antisaccade performance. This study investigates effects on eye movements of procyclidine, an anticholinergic drug often administered to schizophrenic patients. A total of 13 patients completed a double-blind placebo-controlled crossover design, receiving 15 mg procyclidine and placebo. Seven participants received procyclidine first and placebo second, six participants were tested in the reverse order. SPEM and antisaccade (as well as fixation and prosaccade) eye movements were recorded using infrared oculography. Results showed that procyclidine overall, relative to placebo, mildly worsened SPEM performance, as indicated by nonsignificantly reduced gain (p=0.08) and increased frequency of intrusive anticipatory saccades during pursuit (p=0.06). A significant interaction of group and order of administration indicated that procyclidine increased the rate of antisaccade reflexive errors only when administered first; the opposite pattern was observed when placebo was administered first, likely due to the operation of practice effects at second assessment. These findings indicate that acute administration of a clinically relevant dose of procyclidine leads to mild impairments in eye movement performance in schizophrenic patients, suggesting the need to consider this compound in oculomotor studies in schizophrenia. The action of this anticholinergic drug on oculomotor performance is consistent with the hypothesized role of the cholinergic system in the cognitive mechanisms of attention and working memory, processes thought to underlie SPEM and antisaccade performance. Effects of order of administration and practice on the antisaccade task suggest that these factors need to be taken into consideration in future pharmacological studies. [ABSTRACT FROM AUTHOR]

Abstract The present study investigated the reliability and susceptibility to practice effects of oculomotor tasks. Smooth pursuit, fixation, antisaccade, and prosaccade tasks were administered to 31 healthy participants to assess internal consistency (Cronbach's alpha) and within-session practice effects. Twenty-one of these participants were retested after an average interval of 57.86 days to assess temporal stability and between-session practice effects. Internal consistencies were high for most measures, with few within-session performance changes. Test–retest reliabilities of most measures were good. Between-session practice effects were most consistently observed on the antisaccade task, indicated by reduced error rate and improved spatial accuracy at retest. Magnitude of improvement on these measures was related to performance, indicating that poor performers benefited most from repeated assessment. These findings support the trait nature of oculomotor function and point to the need to take into consideration between-session practice effects on the antisaccade task in longitudinal studies. [ABSTRACT FROM AUTHOR]

This study used structural magnetic resonance imaging (MRI) to investigate associations between brain structure and saccadic eye movements. Seventeen healthy subjects underwent structural MRI and infra-red oculographic assessment of a reflexive saccade task. Volumes of prefrontal, premotor, and occipitoparietal cortex, caudate, thalamus, and cerebellar vermis were used as predictors in multiple regression with prosaccade gain as a dependent variable, controlling for whole-brain volume. Using voxel-based morphometry (VBM), gain was entered into correlational analysis with grey matter density. Regression analysis indicated that vermis volumes predicted prosaccade gain. VBM replicated this finding: gain was correlated with grey matter in the left cerebellar hemisphere and vermis. These findings agree with previous studies on the role of the cerebellar vermis in saccadic gain and support the validity of structural neuroimaging methods in elucidating the neural correlates of saccadic eye movements. [Copyright &y& Elsevier]

Performance on a putative psychophysical measure of information processing related to intelligence (Vickers' 1995 Frequency Accrual Speed Test, FAST) was assessed in relation to two psychometric measures of intelligence (Raven's Advanced Progressive Matrices and the Mill Hill vocabulary test). Participants (N = 57) completed the Eysenck Personality Questionnaire — Revised (EPQ-R), and performed the FAST task under either low (70 dB) or high (90 dB) levels of white noise. FAST correlated with Raven's (r = 0.56) and Mill Hill (r = 0.28), as expected. FAST total scores were not affected by personality or personality-by-noise interactions. However, a measure of consistency of FAST performance (i.e. the standard deviation) was correlated negatively with total FAST scores (r = -0.37) and positively with (EPQ-R) extraversion (r = 0.34). The results are discussed in terms of the validity of the FAST to explicate the information processing variables in psychometric intelligence. Copyright © 2001 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]