Overestimation of volatility in schizophrenia and autism? A comparative study using a probabilistic reasoning task.

BACKGROUND AND OBJECTIVES: A plethora of studies has investigated and compared social cognition in autism and schizophrenia ever since both conditions were first described in conjunction more than a century ago. Recent computational theories have proposed similar mechanistic explanations for various symptoms beyond social cognition. They are grounded in the idea of a general misestimation of uncertainty but so far, almost no studies have directly compared both conditions regarding uncertainty processing. The current study aimed to do so with a particular focus on estimation of volatility, i.e. the probability for the environment to change. METHODS: A probabilistic decision-making task and a visual working (meta-)memory task were administered to a sample of 86 participants (19 with a diagnosis of high-functioning autism, 21 with a diagnosis of schizophrenia, and 46 neurotypically developing individuals). RESULTS: While persons with schizophrenia showed lower visual working memory accuracy than neurotypical individuals, no significant group differences were found for metamemory or any of the probabilistic decision-making task variables. Nevertheless, exploratory analyses suggest that there may be an overestimation of volatility in subgroups of participants with autism and schizophrenia. Correlations revealed relationships between different variables reflecting (mis)estimation of uncertainty, visual working memory accuracy and metamemory. LIMITATIONS: Limitations include the comparably small sample sizes of the autism and the schizophrenia group as well as the lack of cognitive ability and clinical symptom measures. CONCLUSIONS: The results of the current study provide partial support for the notion of a general uncertainty misestimation account of autism and schizophrenia.

Psychosis and Psychotic-Like Symptoms Affect Cognitive Abilities but Not Motivation in a Foraging Task.

BACKGROUND AND OBJECTIVE: Goal-directed behavior is a central feature of human functioning. It requires goal appraisal and implicit cost-benefit analyses, i.e., how much effort to invest in the pursuit of a certain goal, against its value and a confidence judgment regarding the chance of attainment. Persons with severe mental illness such as psychosis often struggle with reaching goals. Cognitive deficits, positive symptoms restricting balanced judgment, and negative symptoms such as anhedonia and avolition may compromise goal attainment. The objective of this study was to investigate to what degree symptom severity is related to cognitive abilities, metacognition, and effort-based decision-making in a visual search task. METHODS: Two studies were conducted: study 1: N = 52 (healthy controls), and study 2: N = 46 (23 patients with psychosis/23 matched healthy controls). Symptoms were measured by the CAPE-42 (study 1) and the PANSS (study 2). By using a visual search task, we concomitantly measured (a) accuracy in short-term memory, (b) perceived accuracy by participants making a capture area or confidence interval, and (c) effort by measuring how long one searched for the target. Perseverance was assessed in trials in which the target was omitted and search had to be abandoned. RESULTS: Higher levels of positive symptoms, and having a diagnosis of psychosis, were associated with larger errors in memory. Participants adjusted both their capture area and their search investment to the error of their memory. Perseverance was associated with negative symptoms in study 1 but not in study 2. CONCLUSION: By simultaneously assessing error and confidence in one's memory, as well as effort in search, we found that memory was affected by positive, not negative, symptoms in healthy controls, and was reduced in patients with psychosis. However, impaired memory did not concur with overconfidence or less effort in search, i.e., goal directed behavior was unrelated to symptoms or diagnosis. Metacognition and motivation were neither affected by cognitive abilities nor by negative symptoms. Clinically, this could indicate that struggles with goal directed behavior in psychosis may not solely be dependent on primary illness factors.

A Bayesian model for cross-study differential gene expression.

In this paper we define a hierarchical Bayesian model for microarray expression data collected from several studies and use it to identify genes that show differential expression between two conditions. Key features include shrinkage across both genes and studies, and flexible modeling that allows for interactions between platforms and the estimated effect, as well as concordant and discordant differential expression across studies. We evaluated the performance of our model in a comprehensive fashion, using both artificial data, and a "split-study" validation approach that provides an agnostic assessment of the model's behavior not only under the null hypothesis, but also under a realistic alternative. The simulation results from the artificial data demonstrate the advantages of the Bayesian model. The 1 - AUC values for the Bayesian model are roughly half of the corresponding values for a direct combination of t- and SAM-statistics. Furthermore, the simulations provide guidelines for when the Bayesian model is most likely to be useful. Most noticeably, in small studies the Bayesian model generally outperforms other methods when evaluated by AUC, FDR, and MDR across a range of simulation parameters, and this difference diminishes for larger sample sizes in the individual studies. The split-study validation illustrates appropriate shrinkage of the Bayesian model in the absence of platform-, sample-, and annotation-differences that otherwise complicate experimental data analyses. Finally, we fit our model to four breast cancer studies employing different technologies (cDNA and Affymetrix) to estimate differential expression in estrogen receptor positive tumors versus negative ones. Software and data for reproducing our analysis are publicly available.

Merging two gene-expression studies via cross-platform normalization.

MOTIVATION: Gene-expression microarrays are currently being applied in a variety of biomedical applications. This article considers the problem of how to merge datasets arising from different gene-expression studies of a common organism and phenotype. Of particular interest is how to merge data from different technological platforms. RESULTS: The article makes two contributions to the problem. The first is a simple cross-study normalization method, which is based on linked gene/sample clustering of the given datasets. The second is the introduction and description of several general validation measures that can be used to assess and compare cross-study normalization methods. The proposed normalization method is applied to three existing breast cancer datasets, and is compared to several competing normalization methods using the proposed validation measures. AVAILABILITY: The supplementary materials and XPN Matlab code are publicly available at website: https://genome.unc.edu/xpn