A. Ermakova, Nimrod Gileadi, F. Knolle, A. Justicia, R. Anderson, P. Fletcher, M. Moutoussis, G. Murray
{"title":"Cost Evaluation During Decision-Making in Patients at Early Stages of Psychosis","authors":"A. Ermakova, Nimrod Gileadi, F. Knolle, A. Justicia, R. Anderson, P. Fletcher, M. Moutoussis, G. Murray","doi":"10.1101/225920","DOIUrl":"https://doi.org/10.1101/225920","url":null,"abstract":"Jumping to conclusions during probabilistic reasoning is a cognitive bias reliably observed in psychosis, and linked to delusion formation. Although the reasons for this cognitive bias are unknown, one suggestion is that psychosis patients may view sampling information as more costly. However, previous computational modelling has provided evidence that patients with chronic schizophrenia jump to conclusion because of noisy decision making. We developed a novel version of the classical beads-task, systematically manipulating the cost of information gathering in four blocks. For 31 individuals with early symptoms of psychosis and 31 healthy volunteers, we examined the numbers of ‘draws to decision’ when information sampling had no, a fixed, or an escalating cost. Computational modelling involved estimating a cost of information sampling parameter and a cognitive noise parameter. Overall patients sampled less information than controls. However, group differences in numbers of draws became less prominent at higher cost trials, where less information was sampled. The attenuation of group difference was not due to floor effects, as in the most costly block participants sampled more information than an ideal Bayesian agent. Computational modelling showed that, in the condition with no objective cost to information sampling, patients attributed higher costs to information sampling than controls (Mann-Whiney U=289, p=0.007), with marginal evidence of differences in noise parameter estimates (t=1.86 df=60, p=0.07). In patients, individual differences in severity of psychotic symptoms were statistically significantly associated with higher cost of information sampling (rho=0.6, p=0.001) but not with more cognitive noise (rho=0.27, p=0.14); in controls cognitive noise predicted aspects of schizotypy (preoccupation and distress associated with delusion-like ideation on the Peters Delusion Inventory). Using a psychological manipulation and computational modelling, we provide evidence that early psychosis patients jump to conclusions because of attributing higher costs to sampling information, not because of being primarily noisy decision makers.","PeriodicalId":72664,"journal":{"name":"Computational psychiatry (Cambridge, Mass.)","volume":"97 1","pages":"18 - 39"},"PeriodicalIF":0.0,"publicationDate":"2018-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91079595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christoph Metzner, Tuomo Mäki-Marttunen, B. Zurowski, V. Steuber
{"title":"Modules for Automated Validation and Comparison of Models of Neurophysiological and Neurocognitive Biomarkers of Psychiatric Disorders: ASSRUnit—A Case Study","authors":"Christoph Metzner, Tuomo Mäki-Marttunen, B. Zurowski, V. Steuber","doi":"10.1162/cpsy_a_00015","DOIUrl":"https://doi.org/10.1162/cpsy_a_00015","url":null,"abstract":"The characterization of biomarkers has been a central goal of research in psychiatry over the last years. While most of this research has focused on the identification of biomarkers, using various experimental approaches, it has been recognized that their instantiations, through computational models, have great potential to help us understand and interpret these experimental results. However, the enormous increase in available neurophysiological and neurocognitive as well as computational data also poses new challenges. How can a researcher stay on top of the experimental literature? How can computational modeling data be efficiently compared to experimental data? How can computational modeling most effectively inform experimentalists? Recently, a general scientific framework for the generation of executable tests that automatically compare model results to experimental observations, SciUnit, has been proposed. Here we exploit this framework for research in psychiatry to address the challenges mentioned. We extend the SciUnit framework by adding an experimental database, which contains a comprehensive collection of relevant experimental observations, and a prediction database, which contains a collection of predictions generated by computational models. Together with appropriately designed SciUnit tests and methods to mine and visualize the databases, model data, and test results, this extended framework has the potential to greatly facilitate the use of computational models in psychiatry. As an initial example, we present ASSRUnit, a module for auditory steady-state response deficits in psychiatric disorders.","PeriodicalId":72664,"journal":{"name":"Computational psychiatry (Cambridge, Mass.)","volume":"2 1","pages":"74-91"},"PeriodicalIF":0.0,"publicationDate":"2017-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1162/cpsy_a_00015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43198656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wilson Wen Bin Goh, Judy Chia-Ghee Sng, Jie Yin Yee, Yuen Mei See, Tih-Shih Lee, Limsoon Wong, Jimmy Lee
{"title":"Can Peripheral Blood-Derived Gene Expressions Characterize Individuals at Ultra-high Risk for Psychosis?","authors":"Wilson Wen Bin Goh, Judy Chia-Ghee Sng, Jie Yin Yee, Yuen Mei See, Tih-Shih Lee, Limsoon Wong, Jimmy Lee","doi":"10.1162/CPSY_a_00007","DOIUrl":"10.1162/CPSY_a_00007","url":null,"abstract":"<p><p>The ultra-high risk (UHR) state was originally conceived to identify individuals at imminent risk of developing psychosis. Although recent studies have suggested that most individuals designated UHR do not, they constitute a distinctive group, exhibiting cognitive and functional impairments alongside multiple psychiatric morbidities. UHR characterization using molecular markers may improve understanding, provide novel insight into pathophysiology, and perhaps improve psychosis prediction reliability. Whole-blood gene expressions from 56 UHR subjects and 28 healthy controls are checked for existence of a consistent gene expression profile (signature) underlying UHR, across a variety of normalization and heterogeneity-removal techniques, including simple log-conversion, quantile normalization, gene fuzzy scoring (GFS), and surrogate variable analysis. During functional analysis, consistent and reproducible identification of important genes depends largely on how data are normalized. Normalization techniques that address sample heterogeneity are superior. The best performer, the unsupervised GFS, produced a strong and concise 12-gene signature, enriched for psychosis-associated genes. Importantly, when applied on random subsets of data, classifiers built with GFS are \"meaningful\" in the sense that the classifier models built using genes selected after other forms of normalization do not outperform random ones, but GFS-derived classifiers do. Data normalization can present highly disparate interpretations on biological data. Comparative analysis has shown that GFS is efficient at preserving signals while eliminating noise. Using this, we demonstrate confidently that the UHR designation is well correlated with a distinct blood-based gene signature.</p>","PeriodicalId":72664,"journal":{"name":"Computational psychiatry (Cambridge, Mass.)","volume":"1 ","pages":"168-183"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1162/CPSY_a_00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36379764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Neural Model of Empathic States in Attachment-Based Psychotherapy.","authors":"David Cittern, Abbas Edalat","doi":"10.1162/CPSY_a_00006","DOIUrl":"10.1162/CPSY_a_00006","url":null,"abstract":"<p><p>We build on a neuroanatomical model of how empathic states can motivate caregiving behavior, via empathy circuit-driven activation of regions in the hypothalamus and amygdala, which in turn stimulate a mesolimbic-ventral pallidum pathway, by integrating findings related to the perception of pain in self and others. On this basis, we propose a network to capture states of personal distress and (weak and strong forms of) empathic concern, which are particularly relevant for psychotherapists conducting attachment-based interventions. This model is then extended for the case of self-attachment therapy, in which conceptualized components of the self serve as both the source of and target for empathic resonance. In particular, we consider how states of empathic concern involving an other that is perceived as being closely related to the self might enhance the motivation for self-directed bonding (which in turn is proposed to lead the individual toward more compassionate states) in terms of medial prefrontal cortex-mediated activation of these caregiving pathways. We simulate our model computationally and discuss the interplay between the bonding and empathy protocols of the therapy.</p>","PeriodicalId":72664,"journal":{"name":"Computational psychiatry (Cambridge, Mass.)","volume":"1 ","pages":"132-167"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36379763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Theoretical Framework for Evaluating Psychiatric Research Strategies.","authors":"Kentaro Katahira, Yuichi Yamashita","doi":"10.1162/CPSY_a_00008","DOIUrl":"10.1162/CPSY_a_00008","url":null,"abstract":"<p><p>One of the major goals of basic studies in psychiatry is to find etiological mechanisms or biomarkers of mental disorders. A standard research strategy to pursue this goal is to compare observations of potential factors from patients with those from healthy controls. Classifications of individuals into patient and control groups are generally based on a diagnostic system, such as the <i>Diagnostic and Statistical Manual of Mental Disorders (DSM)</i> or the <i>International Classification of Diseases</i> (<i>ICD</i>). Several flaws in these conventional diagnostic-based approaches have been recognized. The flaws are primarily due to the complexity in the relation between the pathogenetic factors (causes) and disorders: The current diagnostic categories may not reflect the underlying etiological mechanisms. To overcome this difficulty, the National Institute of Mental Health initiated a novel research strategy called Research Domain Criteria (RDoC), which encourages studies to focus on the neurobiological mechanisms and core aspects of behavior rather than to rely on traditional diagnostic categories. However, how RDoC can improve research in psychiatry remains a matter of debate. In this article, we propose a theoretical framework for evaluating psychiatric research strategies, including the conventional diagnostic category-based approaches and the RDoC approach. The proposed framework is based on the statistical modeling of the processes of how the disorder arises from pathogenetic factors. This framework provides the statistical power to quantify how likely relevant pathogenetic factors are to be detected under various research strategies. On the basis of the proposed framework, we can discuss which approach performs better in different types of situations. We present several theoretical and numerical results that highlight the advantages and disadvantages of the strategies. We also demonstrate how a computational model is incorporated into the proposed framework as a generative model of behavioral observations. This demonstration highlights how the computational models contribute to designing psychiatric studies.</p>","PeriodicalId":72664,"journal":{"name":"Computational psychiatry (Cambridge, Mass.)","volume":"1 ","pages":"184-207"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1162/CPSY_a_00008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36379765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Steven M Silverstein, Docia L Demmin, James A Bednar
{"title":"Computational Modeling of Contrast Sensitivity and Orientation Tuning in First-Episode and Chronic Schizophrenia.","authors":"Steven M Silverstein, Docia L Demmin, James A Bednar","doi":"10.1162/CPSY_a_00005","DOIUrl":"10.1162/CPSY_a_00005","url":null,"abstract":"<p><p>Computational modeling is a useful method for generating hypotheses about the contributions of impaired neurobiological mechanisms, and their interactions, to psychopathology. Modeling is being increasingly used to further our understanding of schizophrenia, but to date, it has not been applied to questions regarding the common perceptual disturbances in the disorder. In this article, we model aspects of low-level visual processing and demonstrate how this can lead to testable hypotheses about both the nature of visual abnormalities in schizophrenia and the relationships between the mechanisms underlying these disturbances and psychotic symptoms. Using a model that incorporates retinal, lateral geniculate nucleus (LGN), and V1 activity, as well as gain control in the LGN, homeostatic adaptation in V1, lateral excitation and inhibition in V1, and self-organization of synaptic weights based on Hebbian learning and divisive normalization, we show that (a) prior data indicating <i>increased</i> contrast sensitivity for low-spatial-frequency stimuli in first-episode schizophrenia can be successfully modeled as a function of reduced retinal and LGN efferent activity, leading to overamplification at the cortical level, and (b) prior data on <i>reduced</i> contrast sensitivity <i>and</i> broadened orientation tuning in chronic schizophrenia can be successfully modeled by a combination of reduced V1 lateral inhibition and an increase in the Hebbian learning rate at V1 synapses for LGN input. These models are consistent with many current findings, and they predict several relationships that have not yet been demonstrated. They also have implications for understanding changes in brain and visual function from the first psychotic episode to the chronic stage of illness.</p>","PeriodicalId":72664,"journal":{"name":"Computational psychiatry (Cambridge, Mass.)","volume":"1 ","pages":"102-131"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36379761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andra Mihali, Allison Young, L. Adler, Michael M. Halassa, W. Ma
{"title":"A Low-Level Perceptual Correlate of Behavioral and Clinical Deficits in ADHD","authors":"Andra Mihali, Allison Young, L. Adler, Michael M. Halassa, W. Ma","doi":"10.1101/199216","DOIUrl":"https://doi.org/10.1101/199216","url":null,"abstract":"In many studies of attention-deficit hyperactivity disorder (ADHD), stimulus encoding and processing (per-ceptual function) and response selection (executive function) have been intertwined. To dissociate deficits in these functions, we introduced a task that parametrically varied low-level stimulus features (orientation and color) for fine-grained analysis of perceptual function. It also required participants to switch their attention between feature dimensions on a trial-by-trial basis, thus taxing executive processes. Furthermore, we used a response paradigm that captured task-irrelevant motor output (TIMO), reflecting failures to use the correct stimulus-response rule. ADHD participants had substantially higher perceptual variability than Controls, especially for orientation, as well as higher TIMO. In both ADHD and Controls, TIMO was strongly affected by the switch manipulation. Across participants, the perceptual variability parameter was correlated with TIMO, suggesting that perceptual deficits are associated with executive function deficits. Based on perceptual variability alone, we were able to classify participants into ADHD and Controls with a mean accuracy of about 77%. Participants’ self-reported General Executive Composite score correlated not only with TIMO but also with the perceptual variability parameter. Our results highlight the role of perceptual deficits in ADHD and the usefulness of computational modeling of behavior in dissociating perceptual from executive processes.","PeriodicalId":72664,"journal":{"name":"Computational psychiatry (Cambridge, Mass.)","volume":"137 1","pages":"141 - 163"},"PeriodicalIF":0.0,"publicationDate":"2017-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80986703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Steven M Silverstein, Michael Wibral, William A Phillips
{"title":"Implications of Information Theory for Computational Modeling of Schizophrenia.","authors":"Steven M Silverstein, Michael Wibral, William A Phillips","doi":"10.1162/CPSY_a_00004","DOIUrl":"https://doi.org/10.1162/CPSY_a_00004","url":null,"abstract":"<p><p>Information theory provides a formal framework within which information processing and its disorders can be described. However, information theory has rarely been applied to modeling aspects of the cognitive neuroscience of schizophrenia. The goal of this article is to highlight the benefits of an approach based on information theory, including its recent extensions, for understanding several disrupted neural goal functions as well as related cognitive and symptomatic phenomena in schizophrenia. We begin by demonstrating that foundational concepts from information theory-such as Shannon information, entropy, data compression, block coding, and strategies to increase the signal-to-noise ratio-can be used to provide novel understandings of cognitive impairments in schizophrenia and metrics to evaluate their integrity. We then describe more recent developments in information theory, including the concepts of infomax, coherent infomax, and coding with synergy, to demonstrate how these can be used to develop computational models of schizophrenia-related failures in the tuning of sensory neurons, gain control, perceptual organization, thought organization, selective attention, context processing, predictive coding, and cognitive control. Throughout, we demonstrate how disordered mechanisms may explain both perceptual/cognitive changes and symptom emergence in schizophrenia. Finally, we demonstrate that there is consistency between some information-theoretic concepts and recent discoveries in neurobiology, especially involving the existence of distinct sites for the accumulation of driving input and contextual information prior to their interaction. This convergence can be used to guide future theory, experiment, and treatment development.</p>","PeriodicalId":72664,"journal":{"name":"Computational psychiatry (Cambridge, Mass.)","volume":"1 ","pages":"82-101"},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1162/CPSY_a_00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35961856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Yousefi, Darin D Dougherty, Emad N Eskandar, Alik S Widge, Uri T Eden
{"title":"Estimating Dynamic Signals From Trial Data With Censored Values.","authors":"Ali Yousefi, Darin D Dougherty, Emad N Eskandar, Alik S Widge, Uri T Eden","doi":"10.1162/CPSY_a_00003","DOIUrl":"10.1162/CPSY_a_00003","url":null,"abstract":"<p><p>Censored data occur commonly in trial-structured behavioral experiments and many other forms of longitudinal data. They can lead to severe bias and reduction of statistical power in subsequent analyses. Principled approaches for dealing with censored data, such as data imputation and methods based on the complete data's likelihood, work well for estimating fixed features of statistical models but have not been extended to dynamic measures, such as serial estimates of an underlying latent variable over time. Here we propose an approach to the censored-data problem for dynamic behavioral signals. We developed a state-space modeling framework with a censored observation process at the trial timescale. We then developed a filter algorithm to compute the posterior distribution of the state process using the available data. We showed that special cases of this framework can incorporate the three most common approaches to censored observations: ignoring trials with censored data, imputing the censored data values, or using the full information available in the data likelihood. Finally, we derived a computationally efficient approximate Gaussian filter that is similar in structure to a Kalman filter, but that efficiently accounts for censored data. We compared the performances of these methods in a simulation study and provide recommendations of approaches to use, based on the expected amount of censored data in an experiment. These new techniques can broadly be applied in many research domains in which censored data interfere with estimation, including survival analysis and other clinical trial applications.</p>","PeriodicalId":72664,"journal":{"name":"Computational psychiatry (Cambridge, Mass.)","volume":"1 ","pages":"58-81"},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1162/CPSY_a_00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35962433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}