Altered Perception of Environmental Volatility During Social Learning in Emerging Psychosis.

Paranoid delusions or unfounded beliefs that others intend to deliberately cause harm are a frequent and burdensome symptom in early psychosis, but their emergence and consolidation still remains opaque. Recent theories suggest that overly precise prediction errors lead to an unstable model of the world providing a breeding ground for delusions. Here, we employ a Bayesian approach to test for such an unstable model of the world and investigate the computational mechanisms underlying emerging paranoia. We modelled behaviour of 18 first-episode psychosis patients (FEP), 19 individuals at clinical high risk for psychosis (CHR-P), and 19 healthy controls (HC) during an advice-taking task designed to probe learning about others' changing intentions. We formulated competing hypotheses comparing the standard Hierarchical Gaussian Filter (HGF), a Bayesian belief updating scheme, with a mean-reverting HGF to model an altered perception of volatility. There was a significant group-by-volatility interaction on advice-taking suggesting that CHR-P and FEP displayed reduced adaptability to environmental volatility. Model comparison favored the standard HGF in HC, but the mean-reverting HGF in CHR-P and FEP in line with perceiving increased volatility, although model attributions in CHR-P were heterogeneous. We observed correlations between perceiving increased volatility and positive symptoms generally as well as with frequency of paranoid delusions specifically. Our results suggest that FEP are characterised by a different computational mechanism - perceiving the environment as increasingly volatile - in line with Bayesian accounts of psychosis. This approach may prove useful to investigate heterogeneity in CHR-P and identify vulnerability for transition to psychosis.

Predictive processing: Layer-specific prediction error signals in human cortex.

A new study leveraging advances in high-field fMRI provides evidence that superficial cortical layers in humans play a crucial role in signaling prediction errors, a finding that is consistent with the predictive processing framework.

Predictive Processing: A Circuit Approach to Psychosis.

Predictive processing is a computational framework that aims to explain how the brain processes sensory information by making predictions about the environment and minimizing prediction errors. It can also be used to explain some of the key symptoms of psychotic disorders such as schizophrenia. In recent years, substantial advances have been made in our understanding of the neuronal circuitry that underlies predictive processing in cortex. In this review, we summarize these findings and how they might relate to psychosis and to observed cell type-specific effects of antipsychotic drugs. We argue that quantifying the effects of antipsychotic drugs on specific neuronal circuit elements is a promising approach to understanding not only the mechanism of action of antipsychotic drugs but also psychosis. Finally, we outline some of the key experiments that should be done. The aims of this review are to provide an overview of the current circuit-based approaches to psychosis and to encourage further research in this direction. Expected final online publication date for the Annual Review of Neuroscience, Volume 47 is July 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Sensory processing in humans and mice fluctuates between external and internal modes.

Perception is known to cycle through periods of enhanced and reduced sensitivity to external information. Here, we asked whether such slow fluctuations arise as a noise-related epiphenomenon of limited processing capacity or, alternatively, represent a structured mechanism of perceptual inference. Using 2 large-scale datasets, we found that humans and mice alternate between externally and internally oriented modes of sensory analysis. During external mode, perception aligns more closely with the external sensory information, whereas internal mode is characterized by enhanced biases toward perceptual history. Computational modeling indicated that dynamic changes in mode are enabled by 2 interlinked factors: (i) the integration of subsequent inputs over time and (ii) slow antiphase oscillations in the impact of external sensory information versus internal predictions that are provided by perceptual history. We propose that between-mode fluctuations generate unambiguous error signals that enable optimal inference in volatile environments.

Efficacy and acceptability of third-wave psychotherapies in the treatment of depression: a network meta-analysis of controlled trials.

Introduction: In recent decades, various new psychotherapy approaches have been developed in an effort to overcome issues of non-response, referred to as "third-wave psychotherapies." How third-wave therapies perform in comparison to each other, to classical CBT, or other common comparators in the treatment of depression has not yet been systematically assessed. Methods: We firstly determined the scope of the term "third-wave" by conducting a systematic search. The identified approaches were then used as search terms for the systematic review and network meta-analysis (NMA). We searched MEDLINE, CENTRAL, PsychINFO and Web of Science from inception until 31 July 2022. We assessed randomized controlled trials comparing third-wave psychotherapies to each other, CBT, treatment as usual (TAU), medication management, active control conditions, or waitlist (WL) in adult populations with depressive disorders. The treatments included were acceptance and commitment therapy, behavioral activation, cognitive behavioral analysis system of psychotherapy, dialectical behavioral therapy, mindfulness-based cognitive therapy, meta-cognitive therapy, positive psychotherapy and schema therapy. The primary outcome was depression severity (efficacy) at study endpoint, and the secondary outcome was all-cause discontinuation (acceptability). This review was registered in PROSPERO, identifier CRD42020147535. Results: Of 7,971 search results, 55 trials were included in our NMA (5,827 patients). None of the third-wave therapies were more efficacious than CBT but most were superior to TAU [standardized mean differences (SMD) ranging between 0.42 (95% CI -0.37; 1.19) and 1.25 (0.48; 2.04)]. Meta-cognitive therapy (MCT) was more efficacious than three other third-wave therapy approaches. None of the third-wave treatments were more acceptable than WL or CBT. Twenty-seven percent of the trials were rated as low risk of bias. Confidence in the evidence was largely low according to GRADE. Inconsistency emerged for a small number of comparisons. Interpretations: Third-wave therapies are largely efficacious and acceptable alternatives to CBT when compared to TAU, with few differences between them. The evidence so far does not point toward superiority or inferiority over CBT. Patient-level research may offer possibilities for tailoring individual psychotherapies to the needs of individual patients and future trials should make this data available. The evidence base needs to be broadened by sufficiently powered trials.

Resolving the Delusion Paradox.

BACKGROUND AND HYPOTHESIS: The neurocomputational framework of predictive processing (PP) provides a promising approach to explaining delusions, a key symptom of psychotic disorders. According to PP, the brain makes inferences about the world by weighing prior beliefs against the available sensory data. Mismatches between prior beliefs and sensory data result in prediction errors that may update the brain's model of the world. Psychosis has been associated with reduced weighting of priors relative to the sensory data. However, delusional beliefs are highly resistant to change, suggesting increased rather than decreased weighting of priors. We propose that this "delusion paradox" can be resolved within a hierarchical PP model: Reduced weighting of prior beliefs at low hierarchical levels may be compensated by an increased influence of higher-order beliefs represented at high hierarchical levels, including delusional beliefs. This may sculpt perceptual processing into conformity with delusions and foster their resistance to contradictory evidence. STUDY DESIGN: We review several lines of experimental evidence on low- and high-level processes, and their neurocognitive underpinnings in delusion-related phenotypes and link them to predicted processing. STUDY RESULTS: The reviewed evidence supports the notion of decreased weighting of low-level priors and increased weighting of high-level priors, in both delusional and delusion-prone individuals. Moreover, we highlight the role of prefrontal cortex as a neural basis for the increased weighting of high-level prior beliefs and discuss possible clinical implications of the proposed hierarchical predictive-processing model. CONCLUSIONS: Our review suggests the delusion paradox can be resolved within a hierarchical PP model.

Neural correlates of hierarchical predictive processes in autistic adults.

Bayesian theories of autism spectrum disorders (ASD) suggest that atypical predictive mechanisms could underlie the autistic symptomatology, but little is known about their neural correlates. Twenty-six neurotypical (NT) and 26 autistic adults participated in an fMRI study where they performed an associative learning task in a volatile environment. By inverting a model of perceptual inference, we characterized the neural correlates of hierarchically structured predictions and prediction errors in ASD. Behaviorally, the predictive abilities of autistic adults were intact. Neurally, predictions were encoded hierarchically in both NT and ASD participants and biased their percepts. High-level predictions were following activity levels in a set of regions more closely in ASD than NT. Prediction errors yielded activation in shared regions in NT and ASD, but group differences were found in the anterior cingulate cortex and putamen. This study sheds light on the neural specificities of ASD that might underlie atypical predictive processing.

Sensory and environmental uncertainty in perceptual decision-making.

In perceptual decision-making, uncertainties regarding both noisy sensory information and changing environmental regularities must be considered. We aimed to clarify the relationship between these two sources of uncertainty using a combined motion discrimination and audiovisual reversal learning task with Bayesian modeling. As predicted, the influence of learned beliefs regarding audiovisual associations on perceptual decisions was greater under high sensory uncertainty. Critically, this modulatory effect was larger under high than low environmental uncertainty. Moreover, the degree to which observers relied on learned beliefs when making perceptual decisions depended on their individual tendency to change beliefs. While these findings suggest that weighting of the available sensory information against learned beliefs is modulated by their respective uncertainties, belief learning was not found to rely on sensory uncertainty. Unraveling of these interactive effects of sensory and environmental uncertainties in perception might aid in the understanding of aberrant perceptual inference in psychopathology such as schizophrenia.

No effect of attentional modulation by spatial cueing in a masked numerical priming paradigm using continuous flash suppression (CFS).

One notion emerging from studies on unconscious visual processing is that different "blinding techniques" seem to suppress the conscious perception of stimuli at different levels of the neurocognitive architecture. However, even when only the results from a single suppression method are compared, the picture of the scope and limits of unconscious visual processing remains strikingly heterogeneous, as in the case of continuous flash suppression (CFS). To resolve this issue, it has been suggested that high-level semantic processing under CFS is facilitated whenever interocular suppression is attenuated by the removal of visuospatial attention. In this behavioral study, we aimed to further investigate this "CFS-attenuation-by-inattention" hypothesis in a numerical priming study using spatial cueing. Participants performed a number comparison task on a visible target number ("compare number to five"). Prime-target pairs were either congruent (both numbers smaller, or both larger than five) or incongruent. Based on the "CFS-attenuation-by-inattention" hypothesis, we predicted that reaction times (RTs) for congruent prime-target pairs should be faster than for incongruent ones, but only when the prime was presented at the uncued location. In the invisible condition, we observed no priming effects and thus no evidence in support of the "CFS-attenuation-by-inattention" hypothesis. In the visible condition, we found an inverse effect of prime-target congruency. Our results agree with the notion that the representation of CF-suppressed stimuli is fractionated, and limited to their basic, elemental features, thus precluding semantic processing.

Cross-Modality Evidence for Reduced Choice History Biases in Psychosis-Prone Individuals.

OBJECTIVES: Predictive processing posits that perception emerges from inferential processes within a hierarchical cortical system. Alterations of these processes may result in psychotic experiences, such as hallucinations and delusions. Central to the predictive processing account of psychosis is the notion of aberrant weights attributed to prior information and sensory input. Based on the notion that previous perceptual choices represent a relevant source of prior information, we here asked whether the propensity towards psychotic experiences may be related to altered choice history biases in perceptual decision-making. METHODS: We investigated the relationship between choice history biases in perceptual decision-making and psychosis proneness in the general population. Choice history biases and their adaptation to experimentally induced changes in stimulus serial dependencies were investigated in decision-making tasks with auditory (experiment 1) and visual (experiment 2) stimuli. We further explored a potential compensatory mechanism for reduced choice history biases by reliance on predictive cross-modal cues. RESULTS: In line with our preregistered hypothesis, psychosis proneness was associated with decreased choice history biases in both experiments. This association is generalized across conditions with and without stimulus serial dependencies. We did not find consistent evidence for a compensatory reliance on cue information in psychosis-prone individuals across experiments. CONCLUSIONS: Our results show reduced choice history biases in psychosis proneness. A compensatory mechanism between implicit choice history effects and explicit cue information is not supported unequivocally by our data.

Believing is seeing: The link between paranormal beliefs and perceiving signal in noise.

Research suggests that at the core of paranormal belief formation is a tendency to attribute meaning to ambiguous stimuli. But it is unclear whether this tendency reflects a difference in perceptual sensitivity or a decision bias. Using a two-alternative forced choice task, we tested the relationship between paranormal belief and perceptual sensitivity. Participants were shown two stimuli presented in temporal succession. In one interval an ambiguous Mooney Face (i.e., signal) was presented, in the other interval a scrambled version of the image (i.e., noise) was presented. Participants chose in which of the two intervals the face appeared. Our results revealed that participants with stronger beliefs in paranormal phenomena were less sensitive to discriminating signal from noise. This finding builds on previous research using "yes/no" tasks, but importantly disentangles perceptual sensitivity from response bias and suggests paranormal believers perceive things differently.

The value of confidence: Confidence prediction errors drive value-based learning in the absence of external feedback.

Reinforcement learning algorithms have a long-standing success story in explaining the dynamics of instrumental conditioning in humans and other species. While normative reinforcement learning models are critically dependent on external feedback, recent findings in the field of perceptual learning point to a crucial role of internally generated reinforcement signals based on subjective confidence, when external feedback is not available. Here, we investigated the existence of such confidence-based learning signals in a key domain of reinforcement-based learning: instrumental conditioning. We conducted a value-based decision making experiment which included phases with and without external feedback and in which participants reported their confidence in addition to choices. Behaviorally, we found signatures of self-reinforcement in phases without feedback, reflected in an increase of subjective confidence and choice consistency. To clarify the mechanistic role of confidence in value-based learning, we compared a family of confidence-based learning models with more standard models predicting either no change in value estimates or a devaluation over time when no external reward is provided. We found that confidence-based models indeed outperformed these reference models, whereby the learning signal of the winning model was based on the prediction error between current confidence and a stimulus-unspecific average of previous confidence levels. Interestingly, individuals with more volatile reward-based value updates in the presence of feedback also showed more volatile confidence-based value updates when feedback was not available. Together, our results provide evidence that confidence-based learning signals affect instrumentally learned subjective values in the absence of external feedback.

Experimental Sleep Deprivation Results in Diminished Perceptual Stability Independently of Psychosis Proneness.

Psychotic disorders as well as psychosis proneness in the general population have been associated with perceptual instability, suggesting weakened predictive processing. Sleep disturbances play a prominent role in psychosis and schizophrenia, but it is unclear whether perceptual stability diminishes with sleep deprivation, and whether the effects of sleep deprivation differ as a function of psychosis proneness. In the current study, we aimed to clarify this matter. In this preregistered study, 146 participants successfully completed an intermittent version of the random dot kinematogram (RDK) task and the 21-item Peters Delusion Inventory (PDI-21) to assess perceptual stability and psychosis proneness, respectively. Participants were randomized to sleep either as normal (8 to 9 h in bed) (n = 72; Mage = 24.7, SD = 6.2, 41 women) or to stay awake through the night (n = 74; Mage = 24.8, SD = 5.1, 44 women). Sleep deprivation resulted in diminished perceptual stability, as well as in decreases in perceptual stability over the course of the task. However, we did not observe any association between perceptual stability and PDI-21 scores, nor a tendency for individuals with higher PDI-21 scores to be more vulnerable to sleep-deprivation-induced decreases in perceptual stability. The present study suggests a compromised predictive processing system in the brain after sleep deprivation, but variation in psychosis trait is not related to greater vulnerability to sleep deprivation in our dataset. Further studies in risk groups and patients with psychosis are needed to evaluate whether sleep loss plays a role in the occurrence of objectively measured perceptual-related clinical symptoms.

When seeing is not believing: A mechanistic basis for predictive divergence.

Visual illusions provide a compelling case for the idea that perception and belief may remain incongruent. This can be explained by modular theories of mind, but it is not straightforwardly accommodated by the Predictive Processing framework, which takes perceptual and cognitive predictions to derive from the same underlying inferential hierarchy. Recent insights concerning the neural implementation of Predictive Processing may help elucidate this. Specifically, prior information is proposed to be approximated by mechanisms in both the top-down and bottom-up streams of information processing. While the former is context-dependent and flexible in updating, the latter is context-independent and difficult to revise. We propose that a stable divergence between perception and belief may emerge when flexible prior information at higher hierarchical levels contradicts inflexible prior information at lower ones. This allows Predictive Processing to account for conflicting percepts and beliefs while still maintaining a hierarchical and unitary conception of cognition.

Impaired empathic functioning in chronic depression: Behavioral evidence for the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) model.

The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) model proposes preoperational functioning as a core feature of persistent depressive disorders (PDD). Empathy deficits comprise one aspect. Resulting from childhood maltreatment, empathy deficits may aggravate social isolation, a key factor in the maintenance of depression. CBASP targets empathy by teaching patients to disengage from past experiences and to engage successfully in present social interactions. However, behavioral evidence for empathy deficits in PDD has remained elusive. We reasoned that deficits become apparent only under stress and that these deficits improve after CBASP-treatment. Twenty-two patients and 21 controls performed two parallel versions of the Multifaceted Empathy Test. For stress induction, a negative autobiographical event was presented before performing the task. A neutral event served as control. Fifteen patients performed the experiment twice, before and after a 12-week inpatient CBASP-treatment. Supporting our hypotheses, patients showed reduced empathy under stress, while no group difference was found in the absence of stress. Reduced empathy correlated with the level of re-experiencing negative memories. Pre-post-treatment comparison revealed that the stress-induced empathy deficit improved in patients over time. Post-treatment empathic capacity correlated positively with clinical improvement. Our findings provide empirical support for the CBASP model, but highlight an important new aspect: Empathy is not generally deficient in PDD but becomes impaired under stress. In real-life situations, stress-induced empathy impairments may exacerbate interpersonal conflicts. CBASP's interpersonal focus improved empathy, accompanied by clinical improvement as the model predicts.

Probing the attentional modulation of unconscious processing under interocular suppression in a spatial cueing paradigm.

The debate about the scope and limits of unconscious visual processing under continuous flash suppression (CFS) has created a heterogeneous set of divergent findings that are yet to be reconciled. Attention has been suggested as an important factor in modulating the processing of suppressed visual information under CFS. Specifically, Eo et al. (2016) reported that semantic processing under CFS can be significantly facilitated when spatial attention is diverted away from the suppressed stimulus. Based on event-related potential (ERP) findings involving the N400, they proposed that inattention attenuates interocular suppression and thereby makes semantic processing available unconsciously, potentially reconciling conflicting evidence in the literature. In this study, we aimed to further investigate the "CFS-attenuation-by-inattention" hypothesis using functional magnetic resonance imaging (fMRI) and multivariate pattern analysis (MVPA). We tested whether the decodability of object category increases under CFS when attention is diverted away from the suppressed stimulus in a spatial cueing task. Our results provide no evidence for the "CFS-attenuation-by-inattention" hypothesis, but show higher decoding accuracies for visible stimuli than for invisible stimuli. We discuss the implications of our findings for the important endeavor of trying to reconcile the divergent reports of unconscious processing under CFS.

Non-stimulated regions in early visual cortex encode the contents of conscious visual perception.

Predictions shape our perception. The theory of predictive processing poses that our brains make sense of incoming sensory input by generating predictions, which are sent back from higher to lower levels of the processing hierarchy. These predictions are based on our internal model of the world and enable inferences about the hidden causes of the sensory input data. It has been proposed that conscious perception corresponds to the currently most probable internal model of the world. Accordingly, predictions influencing conscious perception should be fed back from higher to lower levels of the processing hierarchy. Here, we used functional magnetic resonance imaging and multivoxel pattern analysis to show that non-stimulated regions of early visual areas contain information about the conscious perception of an ambiguous visual stimulus. These results indicate that early sensory cortices in the human brain receive predictive feedback signals that reflect the current contents of conscious perception.

Autobiographical Script-Driven Imagery Has No Detectable Effect on Emotion Regulation in Healthy Individuals.

INTRODUCTION: Emotion regulation (ER), the ability to actively modulate one's own emotion reactions, likely depends on the individual's current emotional state. Here, we investigated whether negative emotions induced by an interpersonal autobiographic script affect the neuronal processes underlying ER. METHODS: Twenty healthy participants were recruited and underwent functional magnetic resonance imaging (fMRI) during performance of distancing, a specific ER strategy, while viewing emotionally arousing pictures. Participants were instructed to either naturally experience ("permit" condition) or to actively downregulate ("regulate" condition) their emotional responses to the presented stimuli. Before each of the 4 runs in total, a neutral or negative autobiographical audio script was presented. The negative script comprised an emotionally negative event from childhood or adolescence that represented either emotional abuse or emotional neglect. The second event comprised an everyday neutral situation. We aimed at identifying the neural correlates of ER and their modulation by script-driven imagery. RESULTS: fMRI analyses testing for greater responses in the "regulate" than the "permit" condition replicated previously reported neural correlates of ER in the right dorsolateral prefrontal cortex and the right inferior parietal lobule. A significant ER effect was also observed in the left orbitofrontal cortex. In the amygdala, we found greater responses in the "permit" compared to the "regulate" condition. We did not observe a significant modulation of the ER effects in any of these regions by the negative emotional state induced by autobiographical scripts. Bayesian statistics confirmed the absence of such modulations by providing marginal evidence for null effects. DISCUSSION: While we replicated previously reported neural correlates of ER, we found no evidence for an effect of mood induction with individualized autobiographical scripts on the neural processes underlying ER in healthy participants.

Useful misrepresentation: perception as embodied proactive inference.

According to the predictive processing framework, perception is geared to represent the environment in terms of embodied action opportunities as opposed to objective truth. Here, we argue that such an optimisation is reflected by biases in expectations (i.e., prior predictive information) that facilitate 'useful' inferences of external sensory causes. To support this, we highlight a body of literature suggesting that perception is systematically biased away from accurate estimates under conditions where utility and accuracy conflict with one another. We interpret this to reflect the brain's attempt to adjudicate between conflicting sources of prediction error, as external accuracy is sacrificed to facilitate actions that proactively avoid physiologically surprising outcomes. This carries important theoretical implications and offers new insights into psychopathology.

An active role of inferior frontal cortex in conscious experience.

In the search for the neural correlates of consciousness, it has remained controversial whether prefrontal cortex determines what is consciously experienced or, alternatively, serves only complementary functions, such as introspection or action. Here, we provide converging evidence from computational modeling and two functional magnetic resonance imaging experiments that indicated a key role of inferior frontal cortex in detecting perceptual conflicts caused by ambiguous sensory information. Crucially, the detection of perceptual conflicts by prefrontal cortex turned out to be critical in the process of transforming ambiguous sensory information into unambiguous conscious experiences: in a third experiment, disruption of neural activity in inferior frontal cortex through transcranial magnetic stimulation slowed down the updating of conscious experience that occurs in response to perceptual conflicts. These findings show that inferior frontal cortex actively contributes to the resolution of perceptual ambiguities. Prefrontal cortex is thus causally involved in determining the contents of conscious experience.