Abnormal negative feedback processing in first episode schizophrenia: evidence from an oculomotor rule switching task

Background. Previous studies have shown that patients with schizophrenia are impaired on executive tasks, where positive and negative feedbacks are used to update task rules or switch attention. However, research to date using saccadic tasks has not revealed clear deficits in task switching in these patients. The present study used an oculomotor ‘ rule switching ’ task to investigate the use of negative feedback when switching between task rules in people with schizophrenia. Method. A total of 50 patients with first episode schizophrenia and 25 healthy controls performed a task in which the association between a centrally presented visual cue and the direction of a saccade could change from trial to trial. Rule changes were heralded by an unexpected negative feedback, indicating that the cue-response mapping had reversed. Results. Schizophrenia patients were found to make increased errors following a rule switch, but these were almost entirely the result of executing saccades away from the location at which the negative feedback had been presented on the preceding trial. This impairment in negative feedback processing was independent of IQ. Conclusions. The results not only confirm the existence of a basic deficit in stimulus–response rule switching in schizophrenia, but also suggest that this arises from aberrant processing of response outcomes, resulting in a failure to appropriately update rules. The findings are discussed in the context of neurological and pharmacological abnormalities in the conditions that may disrupt prediction error signalling in schizophrenia

The Ultimate Halo Mass in a LCDM Universe

In the far future of an accelerating LCDM cosmology, the cosmic web of large-scale structure consists of a set of increasingly isolated halos in dynamical equilibrium. We examine the approach of collisionless dark matter to hydrostatic equilibrium using a large N-body simulation evolved to scale factor a = 100, well beyond the vacuum--matter equality epoch, a_eq ~ 0.75, and 53/h Gyr into the future for a concordance model universe (Omega_m ~ 0.3, Omega_Lambda ~ 0.7). The radial phase-space structure of halos -- characterized at a < a_eq by a pair of zero-velocity surfaces that bracket a dynamically active accretion region -- simplifies at a > 10 a_eq when these surfaces merge to create a single zero-velocity surface, clearly defining the halo outer boundary, rhalo, and its enclosed mass, mhalo. This boundary approaches a fixed physical size encompassing a mean interior density ~ 5 times the critical density, similar to the turnaround value in a classical Einstein-deSitter model. We relate mhalo to other scales currently used to define halo mass (m200, mvir, m180b) and find that m200 is approximately half of the total asymptotic cluster mass, while m180b follows the evolution of the inner zero velocity surface for a < 2 but becomes much larger than the total bound mass for a > 3. The radial density profile of all bound halo material is well fit by a truncated Hernquist profile. An NFW profile provides a somewhat better fit interior to r200 but is much too shallow in the range r200 < r < rhalo.Comment: 5 pages, 3 figures, submitted to MNRAS letter

Impaired conscious and preserved unconscious inhibitory processing in recent onset schizophrenia

Background. Impairments in inhibitory function have been found in studies of cognition in schizophrenia. These have been linked to a failure to adequately maintain the task demands in working memory. As response inhibition is known to occur in both voluntary and involuntary processes, an important question is whether both aspects of response inhibition are specifically impaired in people with schizophrenia. Method. The subjects were 33 patients presenting with a first episode of psychosis (27 with schizophrenia and six with schizo-affective disorder) and 24 healthy controls. We administered two motor response tasks: voluntary response inhibition was indexed by the stop-signal task and involuntary response inhibition by the masked priming task. We also administered neuropsychological measures of IQ and executive function to explore their associations with response inhibition. Results. Patients with schizophrenia compared to healthy controls showed significantly increased duration of the voluntary response inhibition process, as indexed by the stop-signal reaction time (SSRT). By contrast, there were no group differences on the pattern of priming on the masked priming task, indicative of intact involuntary response inhibition. Neuropsychological measures revealed that voluntary response inhibition is not necessarily dependent on working memory. Conclusions. These data provide evidence for a specific impairment of voluntary response inhibition in schizophrenia

Stability of the Autism Diagnostic Interview—Revised from Pre-School to Elementary School Age in Children with Autism Spectrum Disorders

This study examined the stability of scores on the ADI-R from pre-school to elementary school age in children with autism spectrum disorders (ASD). Participants were 35 children who, at T1, all had a clinical diagnosis of ASD. On initial assessment (mean age 3.5 years; SD 0.6), all met ADI-R algorithm criteria for autism. ADI-R assessments were repeated at follow up (FU; mean age 10.5 years; SD 0.8). Changes in ADI-R total, domain and ADI-R algorithm item scores were assessed. Twentyeight children continued to score above the ADI-R cut-off for autism at FU, although significant decreases in ADI-R domain and item scores were also found. In conclusion, while classification of children according to ADI-R criteria, generally remained stable between pre-school and elementary school age, many children demonstrated significant improvements in symptom severity

Cognitive tests used in chronic adult human randomised controlled trial micronutrient and phytochemical intervention studies

In recent years there has been a rapid growth of interest in exploring the relationship between nutritional therapies and the maintenance of cognitive function in adulthood. Emerging evidence reveals an increasingly complex picture with respect to the benefits of various food constituents on learning, memory and psychomotor function in adults. However, to date, there has been little consensus in human studies on the range of cognitive domains to be tested or the particular tests to be employed. To illustrate the potential difficulties that this poses, we conducted a systematic review of existing human adult randomised controlled trial (RCT) studies that have investigated the effects of 24 d to 36 months of supplementation with flavonoids and micronutrients on cognitive performance. There were thirty-nine studies employing a total of 121 different cognitive tasks that met the criteria for inclusion. Results showed that less than half of these studies reported positive effects of treatment, with some important cognitive domains either under-represented or not explored at all. Although there was some evidence of sensitivity to nutritional supplementation in a number of domains (for example, executive function, spatial working memory), interpretation is currently difficult given the prevailing 'scattergun approach' for selecting cognitive tests. Specifically, the practice means that it is often difficult to distinguish between a boundary condition for a particular nutrient and a lack of task sensitivity. We argue that for significant future progress to be made, researchers need to pay much closer attention to existing human RCT and animal data, as well as to more basic issues surrounding task sensitivity, statistical power and type I error

A High Throughput Workflow Environment for Cosmological Simulations

The next generation of wide-area sky surveys offer the power to place extremely precise constraints on cosmological parameters and to test the source of cosmic acceleration. These observational programs will employ multiple techniques based on a variety of statistical signatures of galaxies and large-scale structure. These techniques have sources of systematic error that need to be understood at the percent-level in order to fully leverage the power of next-generation catalogs. Simulations of large-scale structure provide the means to characterize these uncertainties. We are using XSEDE resources to produce multiple synthetic sky surveys of galaxies and large-scale structure in support of science analysis for the Dark Energy Survey. In order to scale up our production to the level of fifty 10^10-particle simulations, we are working to embed production control within the Apache Airavata workflow environment. We explain our methods and report how the workflow has reduced production time by 40% compared to manual management.Comment: 8 pages, 5 figures. V2 corrects an error in figure

The Mean and Scatter of the Velocity Dispersion-Optical Richness Relation for maxBCG Galaxy Clusters

The distribution of galaxies in position and velocity around the centers of galaxy clusters encodes important information about cluster mass and structure. Using the maxBCG galaxy cluster catalog identified from imaging data obtained in the Sloan Digital Sky Survey, we study the BCG-galaxy velocity correlation function. By modeling its non-Gaussianity, we measure the mean and scatter in velocity dispersion at fixed richness. The mean velocity dispersion increases from 202+/-10 km/s for small groups to more than 854+/-102 km/s for large clusters. We show the scatter to be at most 40.5+/-3.5%, declining to 14.9+/-9.4% in the richest bins. We test our methods in the C4 cluster catalog, a spectroscopic cluster catalog produced from the Sloan Digital Sky Survey DR2 spectroscopic sample, and in mock galaxy catalogs constructed from N-body simulations. Our methods are robust, measuring the scatter to well within one-sigma of the true value, and the mean to within 10%, in the mock catalogs. By convolving the scatter in velocity dispersion at fixed richness with the observed richness space density function, we measure the velocity dispersion function of the maxBCG galaxy clusters. Although velocity dispersion and richness do not form a true mass-observable relation, the relationship between velocity dispersion and mass is theoretically well characterized and has low scatter. Thus our results provide a key link between theory and observations up to the velocity bias between dark matter and galaxies.Comment: 25 pages, 15 figures, 2 tables, published in Ap

Dissociation of long-term verbal memory and fronto-executive impairment in first-episode psychosis

Background: Verbal memory is frequently and severely affected in schizophrenia and has been implicated as a mediator of poor clinical outcome. Whereas encoding deficits are well demonstrated, it is unclear whether retention is impaired. This distinction is important because accelerated forgetting implies impaired consolidation attributable to medial temporal lobe (MTL) dysfunction whereas impaired encoding and retrieval implicates involvement of prefrontal cortex. Method: We assessed a group of healthy volunteers (n=97) and pre-morbid IQ- and sex-matched first-episode psychosis patients (n=97), the majority of whom developed schizophrenia. We compared performance of verbal learning and recall with measures of visuospatial working memory, planning and attentional set-shifting, and also current IQ. Results: All measures of performance, including verbal memory retention, a memory savings score that accounted for learning impairments, were significantly impaired in the schizophrenia group. The difference between groups for delayed recall remained even after the influence of learning and recall was accounted for. Factor analyses showed that, in patients, all variables except verbal memory retention loaded on a single factor, whereas in controls verbal memory and fronto-executive measures were separable. Conclusions: The results suggest that IQ, executive function and verbal learning deficits in schizophrenia may reflect a common abnormality of information processing in prefrontal cortex rather than specific impairments in different cognitive domains. Verbal memory retention impairments, however, may have a different aetiology

A new generation computerised metacognitive cognitive remediation programme for schizophrenia (CIRCuiTS): a randomised controlled trial

Background: Cognitive remediation (CR) is a psychological therapy which improves cognitive and social functioning in people with schizophrenia. It is now being implemented within routine clinical services and mechanisms of change are being explored. We designed a new generation computerised CR programme, CIRCuiTS, to enhance strategic and metacognitive processing, with an integrated focus on the transfer of cognitive skills to daily living. This large trial tested its feasibility to be delivered in therapist-led and independent sessions, and its efficacy for improved cognitive and social functioning. Methods: A two arm single blind randomised superiority trial comparing CIRCuiTS plus treatment-as-usual (TAU) with TAU alone in 93 people with a diagnosis of schizophrenia. Cognitive, social functioning and symptom outcomes were assessed at pre- and post-therapy and three months later. Results: 85% adhered to CIRCuiTS, completing a median of 28 sessions. There were significant improvements in visual memory at post-treatment (p=0.009) and follow-up (p=0.001), and a trend for improvements in executive function at post-treatment (p=0.056) in favour of the CIRCuiTS group. Community function was also differentially and significantly improved in the CIRCuiTS group at post-treatment (p=0.003) but not follow-up, and was specifically predicted by improved executive functions. Conclusions: CIRCuiTS was beneficial for improving memory and social functioning. Improved executive functioning emerges as a consistent predictor of functional gains and should be considered an important CR target to achieve functional change. A larger-scale effectiveness trial of CIRCuiTS is now indicated