Jumping to conclusions in schizophrenia

Simon L Evans,1 Bruno B Averbeck,2 Nicholas Furl31School of Psychology, University of Sussex, Brighton, East Sussex, UK; 2Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA; 3Department of Psychology, Royal Holloway, University of London, Egham, Surrey, UKAbstract: Schizophrenia is a mental disorder associated with a variety of symptoms, including hallucinations, delusions, social withdrawal, and cognitive dysfunction. Impairments on decision-making tasks are routinely reported: evidence points to a particular deficit in learning from and revising behavior following feedback. In addition, patients tend to make hasty decisions when probabilistic judgments are required. This is known as “jumping to conclusions” (JTC) and has typically been demonstrated by presenting participants with colored beads drawn from one of two “urns” until they claim to be sure which urn the beads are being drawn from (the proportions of colors vary in each urn). Patients tend to make early decisions on this task, and there is evidence to suggest that a hasty decision-making style might be linked to delusion formation and thus be of clinical relevance. Various accounts have been proposed regarding what underlies this behavior. In this review, we briefly introduce the disorder and the decision-making deficits associated with it. We then explore the evidence for each account of JTC in the context of a wider decision-making deficit and then go on to summarize work exploring JTC in healthy controls using pharmacological manipulations and functional imaging. Finally, we assess whether JTC might have a role in therapy.Keywords: ketamine, decision making, delusions, fMRI, urn tas

Social deficits in schizophrenia : pinpointing illness-and task-related factors linked to impairments

La schizophrénie est une maladie invalidante caractérisée par d’importants déficits sociaux qui affecte la capacité de comprendre et d’interagir avec autrui. Plus précisément, des déficits de théorie de l’esprit, c’est-à-dire la capacité de déduire les états mentaux d’autres personnes, sont un facteur prédictif important du niveau de fonctionnement au sein de la communauté en schizophrénie. La délimitation des facteurs sous-jacents aux déficits sociaux dans la schizophrénie est donc cruciale pour améliorer les interventions. L’hétérogénéité de la présentation clinique de la schizophrénie peut influencer les habiletés sociales. Par exemple, plusieurs patients démontrent de l’anxiété sociale, et la présence de cette comorbidité peut influencer davantage leur intégration sociale. De plus, l’hétérogénéité des types de tâches utilisées pour mesurer les déficits sociaux, et notamment le degré de dépendance de ces tâches au contexte, peut affecter les déficits observés dans la schizophrénie. La présente thèse décrit trois études visant à cerner si ces composantes reliées à la pathologie et aux tâches jouent un rôle dans les déficits sociaux en schizophrénie. Cette souligne particulièrement le rôle de la théorie de l’esprit (l’habilité à inférer l’état mental d’autrui), puisque cette habilité a un lien important avec le fonctionnement en schizophrénie. Cette thèse démontre que le trouble d’anxiété social est une comorbidité prévalente dans la schizophrénie, liée à la fois à la représentation clinique de la schizophrénie et au rang social (i.e. comment ils se comparent aux autres vis-à-vis leurs attributs personnels (chapitre 1). Globalement chez les patients atteints de schizophrénie, il est démontré que le traitement du contexte est une composante importante reliée aux déficits de théorie de l’esprit (chapitre 2). De plus, des résultats d’analyse IRMf démontrent que les patients atteints de schizophrénie présentent des activations altérées dans des régions du cerveau, telles que la jonction temporopariétale droite et le cortex cingulaire postérieur, lors du traitement du contexte dans des scénarios sociaux et non sociaux (chapitre 2, chapitre 3). Plus précisément, le chapitre 4 souligne que les patients ont une capacité réduite à moduler les réseaux cérébraux à grande échelle en réponse à des types de contexte différents. Le traitement du contexte peut représenter un déficit fondamental en schizophrénie qui pourrait être une cible lors d’interventions futures visant à améliorer les capacités sociales. Globalement, cette thèse souligne l’importance de prendre en compte l’hétérogénéité à la fois dans la schizophrénie et dans les tâches de la théorie de l’esprit dans de futures recherches sur le traitement social de la schizophrénie, en soulignant spécifiquement le rôle important du trouble de l’anxiété sociale et du traitement du contexte.Schizophrenia is a highly disabling disorder characterized by significant social deficits that impair one’s ability to interact with and understand others. Specifically, impairments in Theory of Mind, i.e. the ability to infer the mental states of others, are an important predictor of community functioning in schizophrenia. Delineating the factors underlying social deficits in schizophrenia is thus crucial to developing improved treatment targets for functioning. Heterogeneity in the clinical presentation of schizophrenia may influence one’s socia l abilities. For instance, many patients also present with social anxiety, and this comorbid presentation may further affect their abilities to integrate in the social world. Additionally, heterogeneity in the types of tasks used to measure social deficits, and notably, the degree to which these tasks rely on context, may affect deficits observed in schizophrenia. The present thesis describes three studies that aim to pinpoint whether these illness- and task-related components play a role in social deficits in schizophrenia, with a particular focus on Theory of Mind abilities. This thesis demonstrates that social anxiety disorder is a prevalent comorbidity in schizophrenia related to both the clinical presentation of schizophrenia and to social rank (i.e. how they rank themselves compared to others on personal attributes; Chapter 1). In patients with schizophrenia overall, results also highlight that context processing is an important component related to deficits on Theory of Mind tasks (Chapter 2). Additionally, fMRI results demonstrate that patients with schizophrenia display altered activation in brain regions (e.g. right temporo-parietal junction, posterior cingulate cortex) during processing context in social and non-social scenarios (Chapter 2, Chapter 3). Specifically, Chapter 3 highlights that patients have a reduced ability to modulate large-scale brain networks in response to different types of context. Context processing may represent a core deficit in schizophrenia that could be a target in future interventions to improve social abilities. Overall, this thesis underlines the importance of considering heterogeneity in both schizophrenia and in Theory of Mind tasks in future research of social processing in schizophrenia, specifically highlighting the important role of social anxiety disorder and context processing

Cognitive and neural mechanisms underlying post-decision processing

Contested issues, such as climate change, can generate polarised and rigid views. A prominent source of entrenched beliefs is confirmation bias, where evidence against one’s position is selectively disregarded. Although an extensive literature has documented this altered processing of new information, the underlying cognitive, computational and neuronal mechanisms remain unknown. In this thesis, I explore the mechanisms underlying this altered processing of new information, its relation to broader societal attitudes, and finally I test an intervention to alleviate this cognitive bias. In a first set of studies, I combined human magnetoencephalography (MEG) with behavioural and neural modelling to identify the drivers of altered post-decision evidence integration. I show that high confidence in an initial decision leads to a striking modulation of post-decision neural processing, such that integration of confirmatory evidence is amplified while disconfirmatory evidence processing is abolished. This indicates that confidence shapes a selective neural gating for choice-consistent information, reducing the likelihood of changes of mind. Confirmation bias has received most attention for its potential contribution to societal polarization and entrenchment. Therefore, in a second set of studies, I tested whether cognitive alterations in post-decision evidence integration are related to broader societal attitudes, such as dogmatic and rigid political beliefs. I found that dogmatic participants showed a reduced sensitivity for disconfirming post-decision evidence (i.e. a stronger confirmation bias) and a reduced tendency to actively seek out corrective information. In a final study, I tested a metacognitive training procedure as a potential intervention to counteract confirmation bias. This training improved participants’ metacognitive ability and through this boosted their processing of post-decision evidence, both on a behavioural and neural level. These studies provide a novel mechanistic understanding of confirmation bias, exemplify the potential societal implications of altered post-decision processing and enabled an evidence-based intervention to counteract this cognitive bias

Investigation of hemispheric asymmetry in reasoning with HD-tDCS and fMRI

Studies on multiple patient groups suggest that reasoning has a hemispheric asymmetry component. Previously, we proposed that neural networks in the left hemisphere are driven toward increasing and maintaining certainty, while right frontal networks prioritize congruence between beliefs and evidence. We tested the predictions of this framework with two high definition transcranial direct current stimulation (HD-tDCS) experiments and one functional magnetic resonance imaging (fMRI) experiment. In both HD-tDCS studies, we aimed to induce (or amplify) hemispheric asymmetry in healthy participants as they completed novel reasoning tasks. Each participant completed three tDCS sessions: a LH-bias session, in which the anode was placed over the left inferior frontal gyrus (IFG; BA45) and the cathode over the right IFG; a RH-bias session, in which the anode was placed over the right IFG and the cathode over the left IFG; and a sham session, which served as a control. In the first HD-tDCS experiment, participants (N=26) completed a probabilistic inference task that required the integration of evidence and one’s prior background knowledge. Consistent with predictions, we found that the intensity of RH-bias stimulation was associated with 1) collecting more evidence, 2) adopting a higher threshold for stopping evidence collection, and 3) making less certain guesses than an ideal Bayesian updater during the evidence presentation. Contrary to predictions, we found that greater LH-bias intensity was associated with more evidence collection, and LH-bias stimulation was associated with greater belief backtracks after encountering conflicting evidence than RH-bias or sham stimulation. The second HD-tDCS experiment followed a similar stimulation protocol but used reasoning problems that were more deeply embedded in real-world contexts in order to create more salient belief-evidence conflicts. During each stimulation session, 24 participants 1) judged whether a criminal suspect was guilty or not guilty based on crime scene evidence, 2) judged whether or not to pass a law based on arguments in favor and in opposition to it, and 3) judged whether a news headline was real or fake. We found that RH-bias stimulation reduced belief polarization after conflict, which was consistent with our predictions. Similarly, when evidence conflicted participants’ strong beliefs, they backtracked on their beliefs more under RH-bias stimulation compared to sham stimulation and, albeit to a lesser extent, compared to LH-bias stimulation. Under RH-bias stimulation, participants were less likely to judge real news headlines as being real, which resulted in poorer discrimination of real vs. fake headlines compared to sham and LH-bias stimulation. Finally, in the fMRI experiment, we examined lateralization in frontal anatomical regions for contrasts that we predicted to be more left-lateralized or more right-lateralized. Participants (N=36) completed a modified version of the state guessing task that was used in the first tDCS experiment. Consistent with predictions, contrasts involving uncertainty and belief advances were generally more left-lateralized and contrasts involving conflicting evidence and belief backtracks were more right-lateralized. We show that HD-tDCS can alter belief updating in healthy individuals in a way that is consistent with the patient literature, but additional experiments are necessary to disentangle the causal relationships between different reasoning biases and neural activity in left and right frontal neural networks

Strategic control processes in episodic memory and beyond

The evaluation of past experience is influenced both by the strength of retrieved memories and factors in the immediate retrieval environment, including emphasised goals and cued expectations. However, the laboratory study of episodic memory has neglected such environmental influences, despite their overt contribution to real-world decision outcomes. The aim of this PhD thesis was to rectify this neglect, and clarify the interaction of memory evidence and environmental strategies in the service of strategic memory control. A related aim was to investigate whether control processes identified in the isolated domain of episodic memory in fact performed a more general or “cross-domain” function. An initial series of behavioural experiments (Experiments 1-3) elucidated an overlooked source of strategic bias in the standard recognition environment – implicit goal emphasis imparted by question format. Experiment 4 investigated whether the question bias was commonly enacted across different domains of evaluation, yielding modest evidence in favour of this underlying cross-domain function. Experiment 5 instantiated more explicit manipulation of goal emphasis and cued expectation, and recovered independent and opposing strategic effects of these two environmental factors, emerging across episodic and non-episodic domains. Experiment 6 employed a simultaneous EEG-fMRI approach to elucidate the neural correlates of memory control, identifying a modulation of the late positive event-related potential during the resolution of mnemonic conflict, which was sourced to BOLD variation in regions of the rostral cingulate zone and intraparietal sulcus. Experiment 7 used pupillometry to examine pupil-linked autonomic systems that have also been implicated in memory control, and isolated two distinct components of the dilation response evoked during environmental conflict – an “early amplitude” unexpected familiarity effect and a “trailing slope” uncertainty effect. The findings illuminate the cross-domain underpinnings of an adaptive memory control system, evidenced in behaviour and across different functional neuroimaging modalities, and across episodic and non-episodic domains of evaluation

Hierarchical Bayesian Inference in Psychosis

Schizophrenia is a severe mental illness that affects millions of people worldwide and can have a drastic impact on a patient’s life. The illness is characterised by symptoms such as hallucinations and delusions. In recent years, a powerful theoretical framework has been developed to understand better how such symptoms emerge, the predictive coding account of psychosis. In this thesis, I cast different symptoms of psychosis as instances of hierarchical Bayesian inference in a series of studies. The first study examined the question of how persecutory delusions emerge in early psychosis. We derived hypotheses based on previous literature and simulations and tested them empirically in a sample of 18 first-episode psychosis patients, 19 individuals at clinical high risk for psychosis (CHR) and 19 matched healthy controls (HC). Our results suggest that emerging psychosis may be accompanied by an altered perception of environmental volatility. In a second study, this modelling approach was applied to delusions more broadly in a large dataset including 261 patients with psychotic disorders and 56 HC to examine the relationship between delusions and reasoning biases that were previously reported in psychosis. The results of this study suggest that beliefs of patients with psychotic disorders were characterised by increased belief instability, which explained increased belief updating in light of disconfirmatory evidence. We also assessed the clinical utility of this approach by testing its ability to predict treatment response to a psychotherapeutic intervention and found that the parameters of the computational model were able to predict treatment outcome in individual patients. Lastly, in a final study, we modelled brain activity during an implicit sensory learning task in a third independent sample of 38 CHR, 18 early-illness schizophrenia patients, and 44 HC to assess the biological plausibility of this approach. Our results suggest that hierarchical precision-weighted prediction errors derived from the model modulate electroencephalography (EEG) amplitudes. Moreover, we found not only differences in the expression of precision-weighted prediction errors between schizophrenia patients and HC, but also between CHR, who later converted to a psychotic disorder, and non-converters. Jointly, this work demonstrates that this computational approach may not only be conceptually useful to understand the computational mechanisms underlying psychosis, but also clinically relevant and biologically plausible

The cybernetic Bayesian brain: from interoceptive inference to sensorimotor contingencies

Is there a single principle by which neural operations can account for perception, cognition, action, and even consciousness? A strong candidate is now taking shape in the form of “predictive processing”. On this theory, brains engage in predictive inference on the causes of sensory inputs by continuous minimization of prediction errors or informational “free energy”. Predictive processing can account, supposedly, not only for perception, but also for action and for the essential contribution of the body and environment in structuring sensorimotor interactions. In this paper I draw together some recent developments within predictive processing that involve predictive modelling of internal physiological states (interoceptive inference), and integration with “enactive” and “embodied” approaches to cognitive science (predictive perception of sensorimotor contingencies). The upshot is a development of predictive processing that originates, not in Helmholtzian perception-as-inference, but rather in 20th-century cybernetic principles that emphasized homeostasis and predictive control. This way of thinking leads to (i) a new view of emotion as active interoceptive inference; (ii) a common predictive framework linking experiences of body ownership, emotion, and exteroceptive perception; (iii) distinct interpretations of active inference as involving disruptive and disambiguatory—not just confirmatory—actions to test perceptual hypotheses; (iv) a neurocognitive operationalization of the “mastery of sensorimotor contingencies” (where sensorimotor contingencies reflect the rules governing sensory changes produced by various actions); and (v) an account of the sense of subjective reality of perceptual contents (“perceptual presence”) in terms of the extent to which predictive models encode potential sensorimotor relations (this being “counterfactual richness”). This is rich and varied territory, and surveying its landmarks emphasizes the need for experimental tests of its key contributions

Disadvantageous associations: Reversible spatial cueing effects in a discrimination task

Current theories describe learning in terms of cognitive or associative mechanisms. To assess whether cognitive mechanisms interact with automaticity of associative processes we devised a shape-discrimination task in which participants received both explicit instructions and implicit information. Instructions further allowed for the inference that a first event would precede the target. Albeit irrelevant to respond, this event acted as response prime and implicit spatial cue (i.e. it predicted target location). To modulate cognitive involvement, in three experiments we manipulated modality and salience of the spatial cue. Results always showed evidence for a priming effect, confirming that the first stimulus was never ignored. More importantly, although participants failed to consciously recognize the association, responses to spatially cued trials became either slower or faster depending on salience of the first event. These findings provide an empirical demonstration that cognitive and associative learning mechanisms functionally co-exist and interact to regulate behaviour

Is conscious perception a series of discrete temporal frames?

This paper reviews proposals that conscious perception consists, in whole or part, of successive discrete temporal frames on the sub-second time scale, each frame containing information registered as simultaneous or static. Although the idea of discrete frames in conscious perception cannot be regarded as falsified, there are many problems. Evidence does not consistently support any proposed duration or range of durations for frames. EEG waveforms provide evidence of periodicity in brain activity, but not necessarily in conscious perception. Temporal properties of perceptual processes are flexible in response to competing processing demands, which is hard to reconcile with the relative inflexibility of regular frames. There are also problems concerning the definition of frames, the need for informational connections between frames, the means by which boundaries between frames are established, and the apparent requirement for a storage buffer for information awaiting entry to the next frame