The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. METHODS: The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. RESULTS: There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. CONCLUSIONS: The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. FUNDING: This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).

A social inference model of idealization and devaluation.

People often form polarized beliefs, imbuing objects (e.g., themselves or others) with unambiguously positive or negative qualities. In clinical settings, this is referred to as dichotomous thinking or "splitting" and is a feature of several psychiatric disorders. Here, we introduce a Bayesian model of splitting that parameterizes a tendency to rigidly categorize objects as either entirely "Bad" or "Good," rather than to flexibly learn dispositions along a continuous scale. Distinct from the previous descriptive theories, the model makes quantitative predictions about how dichotomous beliefs emerge and are updated in light of new information. Specifically, the model addresses how splitting is context-dependent, yet exhibits stability across time. A key model feature is that phases of devaluation and/or idealization are consolidated by rationally attributing counter-evidence to external factors. For example, when another person is idealized, their less-than-perfect behavior is attributed to unfavorable external circumstances. However, sufficient counter-evidence can trigger switches of polarity, producing bistable dynamics. We show that the model can be fitted to empirical data, to measure individual susceptibility to relational instability. For example, we find that a latent categorical belief that others are "Good" accounts for less changeable, and more certain, character impressions of benevolent as opposed to malevolent others among healthy participants. By comparison, character impressions made by participants with borderline personality disorder reveal significantly higher and more symmetric splitting. The generative framework proposed invites applications for modeling oscillatory relational and affective dynamics in psychotherapeutic contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Self-reported childhood family adversity is linked to an attenuated gain of trust during adolescence.

A longstanding proposal in developmental research is that childhood family experiences provide a template that shapes a capacity for trust-based social relationships. We leveraged longitudinal data from a cohort of healthy adolescents (n = 570, aged 14-25), which included decision-making and psychometric data, to characterise normative developmental trajectories of trust behaviour and inter-individual differences therein. Extending on previous cross-sectional findings from the same cohort, we show that a task-based measure of trust increases longitudinally from adolescence into young adulthood. Computational modelling suggests this is due to a decrease in social risk aversion. Self-reported family adversity attenuates this developmental gain in trust behaviour, and within our computational model, this relates to a higher 'irritability' parameter in those reporting greater adversity. Unconditional trust at measurement time point T1 predicts the longitudinal trajectory of self-reported peer relation quality, particularly so for those with higher family adversity, consistent with trust acting as a resilience factor.

Testing hypotheses about the harm that capitalism causes to the mind and brain: a theoretical framework for neuroscience research.

In this paper, we will attempt to outline the key ideas of a theoretical framework for neuroscience research that reflects critically on the neoliberal capitalist context. We argue that neuroscience can and should illuminate the effects of neoliberal capitalism on the brains and minds of the population living under such socioeconomic systems. Firstly, we review the available empirical research indicating that the socio-economic environment is harmful to minds and brains. We, then, describe the effects of the capitalist context on neuroscience itself by presenting how it has been influenced historically. In order to set out a theoretical framework that can generate neuroscientific hypotheses with regards to the effects of the capitalist context on brains and minds, we suggest a categorization of the effects, namely deprivation, isolation and intersectional effects. We also argue in favor of a neurodiversity perspective [as opposed to the dominant model of conceptualizing neural (mal-)functioning] and for a perspective that takes into account brain plasticity and potential for change and adaptation. Lastly, we discuss the specific needs for future research as well as a frame for post-capitalist research.

The neurobiology of functional neurological disorders characterised by impaired awareness.

We review the neurobiology of Functional Neurological Disorders (FND), i.e., neurological disorders not explained by currently identifiable histopathological processes, in order to focus on those characterised by impaired awareness (functionally impaired awareness disorders, FIAD), and especially, on the paradigmatic case of Resignation Syndrome (RS). We thus provide an improved more integrated theory of FIAD, able to guide both research priorities and the diagnostic formulation of FIAD. We systematically address the diverse spectrum of clinical presentations of FND with impaired awareness, and offer a new framework for understanding FIAD. We find that unraveling the historical development of neurobiological theory of FIAD is of paramount importance for its current understanding. Then, we integrate contemporary clinical material in order to contextualise the neurobiology of FIAD within social, cultural, and psychological perspectives. We thus review neuro-computational insights in FND in general, to arrive at a more coherent account of FIAD. FIAD may be based on maladaptive predictive coding, shaped by stress, attention, uncertainty, and, ultimately, neurally encoded beliefs and their updates. We also critically appraise arguments in support of and against such Bayesian models. Finally, we discuss implications of our theoretical account and provide pointers towards an improved clinical diagnostic formulation of FIAD. We suggest directions for future research towards a more unified theory on which future interventions and management strategies could be based, as effective treatments and clinical trial evidence remain limited.

Action selection in early stages of psychosis: an active inference approach.

BACKGROUND: To interact successfully with their environment, humans need to build a model to make sense of noisy and ambiguous inputs. An inaccurate model, as suggested to be the case for people with psychosis, disturbs optimal action selection. Recent computational models, such as active inference, have emphasized the importance of action selection, treating it as a key part of the inferential process. Based on an active inference framework, we sought to evaluate previous knowledge and belief precision in an action-based task, given that alterations in these parameters have been linked to the development of psychotic symptoms. We further sought to determine whether task performance and modelling parameters would be suitable for classification of patients and controls. METHODS: Twenty-three individuals with an at-risk mental state, 26 patients with first-episode psychosis and 31 controls completed a probabilistic task in which action choice (go/no-go) was dissociated from outcome valence (gain or loss). We evaluated group differences in performance and active inference model parameters and performed receiver operating characteristic (ROC) analyses to assess group classification. RESULTS: We found reduced overall performance in patients with psychosis. Active inference modelling revealed that patients showed increased forgetting, reduced confidence in policy selection and less optimal general choice behaviour, with poorer action-state associations. Importantly, ROC analysis showed fair-to-good classification performance for all groups, when combining modelling parameters and performance measures. LIMITATIONS: The sample size is moderate. CONCLUSION: Active inference modelling of this task provides further explanation for dysfunctional mechanisms underlying decision-making in psychosis and may be relevant for future research on the development of biomarkers for early identification of psychosis.

The Scientific Study of Consciousness Cannot and Should Not Be Morally Neutral.

A target question for the scientific study of consciousness is how dimensions of consciousness, such as the ability to feel pain and pleasure or reflect on one's own experience, vary in different states and animal species. Considering the tight link between consciousness and moral status, answers to these questions have implications for law and ethics. Here we point out that given this link, the scientific community studying consciousness may face implicit pressure to carry out certain research programs or interpret results in ways that justify current norms rather than challenge them. We show that because consciousness largely determines moral status, the use of nonhuman animals in the scientific study of consciousness introduces a direct conflict between scientific relevance and ethics-the more scientifically valuable an animal model is for studying consciousness, the more difficult it becomes to ethically justify compromises to its well-being for consciousness research. Finally, in light of these considerations, we call for a discussion of the immediate ethical corollaries of the body of knowledge that has accumulated and for a more explicit consideration of the role of ideology and ethics in the scientific study of consciousness.

The computational relationship between reinforcement learning, social inference, and paranoia.

Theoretical accounts suggest heightened uncertainty about the state of the world underpin aberrant belief updates, which in turn increase the risk of developing a persecutory delusion. However, this raises the question as to how an agent's uncertainty may relate to the precise phenomenology of paranoia, as opposed to other qualitatively different forms of belief. We tested whether the same population (n = 693) responded similarly to non-social and social contingency changes in a probabilistic reversal learning task and a modified repeated reversal Dictator game, and the impact of paranoia on both. We fitted computational models that included closely related parameters that quantified the rigidity across contingency reversals and the uncertainty about the environment/partner. Consistent with prior work we show that paranoia was associated with uncertainty around a partner's behavioural policy and rigidity in harmful intent attributions in the social task. In the non-social task we found that pre-existing paranoia was associated with larger decision temperatures and commitment to suboptimal cards. We show relationships between decision temperature in the non-social task and priors over harmful intent attributions and uncertainty over beliefs about partners in the social task. Our results converge across both classes of model, suggesting paranoia is associated with a general uncertainty over the state of the world (and agents within it) that takes longer to resolve, although we demonstrate that this uncertainty is expressed asymmetrically in social contexts. Our model and data allow the representation of sociocognitive mechanisms that explain persecutory delusions and provide testable, phenomenologically relevant predictions for causal experiments.

Self-esteem depends on beliefs about the rate of change of social approval.

A major challenge in understanding the neurobiological basis of psychiatric disorders is rigorously quantifying subjective metrics that lie at the core of mental illness, such as low self-esteem. Self-esteem can be conceptualized as a 'gauge of social approval' that increases in response to approval and decreases in response to disapproval. Computational studies have shown that learning signals that represent the difference between received and expected social approval drive changes in self-esteem. However, it is unclear whether self-esteem based on social approval should be understood as a value updated through associative learning, or as a belief about approval, updated by new evidence depending on how strongly it is held. Our results show that belief-based models explain self-esteem dynamics in response to social evaluation better than associative learning models. Importantly, they suggest that in the short term, self-esteem signals the direction and rate of change of one's beliefs about approval within a group, rather than one's social position.

A Computational Analysis of Abnormal Belief Updating Processes and Their Association With Psychotic Experiences and Childhood Trauma in a UK Birth Cohort.

BACKGROUND: Psychotic experiences emerge from abnormalities in perception and belief formation and occur more commonly in those experiencing childhood trauma. However, which precise aspects of belief formation are atypical in psychosis is not well understood. We used a computational modeling approach to characterize belief updating in young adults in the general population, examine their relationship with psychotic outcomes and trauma, and determine the extent to which they mediate the trauma-psychosis relationship. METHODS: We used data from 3360 individuals from the Avon Longitudinal Study of Parents and Children birth cohort who completed assessments for psychotic outcomes, depression, anxiety, and two belief updating tasks at age 24 and had data available on traumatic events assessed from birth to late adolescence. Unadjusted and adjusted regression and counterfactual mediation methods were used for the analyses. RESULTS: Basic behavioral measures of belief updating (draws-to-decision and disconfirmatory updating) were not associated with psychotic experiences. However, computational modeling revealed an association between increased decision noise with both psychotic experiences and trauma exposure, although <3% of the trauma-psychotic experience association was mediated by decision noise. Belief updating measures were also associated with intelligence and sociodemographic characteristics, confounding most of the associations with psychotic experiences. There was little evidence that belief updating parameters were differentially associated with delusions compared with hallucinations or that they were differentially associated with psychotic outcomes compared with depression or anxiety. CONCLUSIONS: These findings challenge the hypothesis that atypical belief updating mechanisms (as indexed by the computational models and behavioral measures we used) underlie the development of psychotic phenomena.

Assigning the right credit to the wrong action: compulsivity in the general population is associated with augmented outcome-irrelevant value-based learning.

Compulsive behavior is enacted under a belief that a specific act controls the likelihood of an undesired future event. Compulsive behaviors are widespread in the general population despite having no causal relationship with events they aspire to influence. In the current study, we tested whether there is an increased tendency to assign value to aspects of a task that do not predict an outcome (i.e., outcome-irrelevant learning) among individuals with compulsive tendencies. We studied 514 healthy individuals who completed self-report compulsivity, anxiety, depression, and schizotypal measurements, and a well-established reinforcement-learning task (i.e., the two-step task). As expected, we found a positive relationship between compulsivity and outcome-irrelevant learning. Specifically, individuals who reported having stronger compulsive tendencies (e.g., washing, checking, grooming) also tended to assign value to response keys and stimuli locations that did not predict an outcome. Controlling for overall goal-directed abilities and the co-occurrence of anxious, depressive, or schizotypal tendencies did not impact these associations. These findings indicate that outcome-irrelevant learning processes may contribute to the expression of compulsivity in a general population setting. We highlight the need for future research on the formation of non-veridical action-outcome associations as a factor related to the occurrence and maintenance of compulsive behavior.

A Reduced Self-Positive Belief Underpins Greater Sensitivity to Negative Evaluation in Socially Anxious Individuals.

Positive self-beliefs are important for well-being, and are influenced by how others evaluate us during social interactions. Mechanistic accounts of self-beliefs have mostly relied on associative learning models. These account for choice behaviour but not for the explicit beliefs that trouble socially anxious patients. Neither do they speak to self-schemas, which underpin vulnerability according to psychological research. Here, we compared belief-based and associative computational models of social-evaluation, in individuals that varied in fear of negative evaluation (FNE), a core symptom of social anxiety. We used a novel analytic approach, 'clinically informed model-fitting', to determine the influence of FNE symptom scores on model parameters. We found that high-FNE participants learn more easily from negative feedback about themselves, manifesting in greater self-negative learning rates. Crucially, we provide evidence that this bias is underpinned by an overall reduced belief about self-positive attributes. The study population could be characterized equally well by belief-based or associative models, however large individual differences in model likelihood indicated that some individuals relied more on an associative (model-free), while others more on a belief-guided strategy. Our findings have therapeutic importance, as positive belief activation may be used to specifically modulate learning. AUTHOR SUMMARY: Understanding how we form and maintain positive self-beliefs is crucial to understanding how things go awry in disorders such as social anxiety. The loss of positive self-belief in social anxiety, especially in inter-personal contexts, is thought to be related to how we integrate evaluative information that we receive from others. We frame this social information integration as a learning problem and ask how people learn whether someone approves of them or not. We thus elucidate why the decrease in positive evaluations manifests only for the self, but not for an unknown other, given the same information. We investigated the mechanics of this learning using a novel computational modelling approach, comparing models that treat the learning process as series of stimulusresponse associations with models that treat learning as updating of beliefs about the self (or another). We show that both models characterise the process well and that individuals higher in symptoms of social anxiety learn more from negative information specifically about the self. Crucially, we provide evidence that this originates from a reduction in the amount of positive attributes that are activated when the individual is placed in a social evaluative context.

Preference uncertainty accounts for developmental effects on susceptibility to peer influence in adolescence.

Adolescents are prone to social influence from peers, with implications for development, both adaptive and maladaptive. Here, using a computer-based paradigm, we replicate a cross-sectional effect of more susceptibility to peer influence in a large dataset of adolescents 14 to 24 years old. Crucially, we extend this finding by adopting a longitudinal perspective, showing that a within-person susceptibility to social influence decreases over a 1.5 year follow-up time period. Exploiting this longitudinal design, we show that susceptibility to social influences at baseline predicts an improvement in peer relations over the follow-up period. Using a Bayesian computational model, we demonstrate that in younger adolescents a greater tendency to adopt others' preferences arises out of a higher uncertainty about their own preferences in the paradigmatic case of delay discounting (a phenomenon called 'preference uncertainty'). This preference uncertainty decreases over time and, in turn, leads to a reduced susceptibility of one's own behaviour to an influence from others. Neuro-developmentally, we show that a measure of myelination within medial prefrontal cortex, estimated at baseline, predicts a developmental decrease in preference uncertainty at follow-up. Thus, using computational and neural evidence, we reveal adaptive mechanisms underpinning susceptibility to social influence during adolescence.

Simulating the computational mechanisms of cognitive and behavioral psychotherapeutic interventions: insights from active inference.

Cognitive-behavioral therapy (CBT) leverages interactions between thoughts, feelings, and behaviors. To deepen understanding of these interactions, we present a computational (active inference) model of CBT that allows formal simulations of interactions between cognitive interventions (i.e., cognitive restructuring) and behavioral interventions (i.e., exposure) in producing adaptive behavior change (i.e., reducing maladaptive avoidance behavior). Using spider phobia as a concrete example of maladaptive avoidance more generally, we show simulations indicating that when conscious beliefs about safety/danger have strong interactions with affective/behavioral outcomes, behavioral change during exposure therapy is mediated by changes in these beliefs, preventing generalization. In contrast, when these interactions are weakened, and cognitive restructuring only induces belief uncertainty (as opposed to strong safety beliefs), behavior change leads to generalized learning (i.e., "over-writing" the implicit beliefs about action-outcome mappings that directly produce avoidance). The individual is therefore equipped to face any new context, safe or dangerous, remaining in a content state without the need for avoidance behavior-increasing resilience from a CBT perspective. These results show how the same changes in behavior during CBT can be due to distinct underlying mechanisms; they predict lower rates of relapse when cognitive interventions focus on inducing uncertainty and on reducing the effects of automatic negative thoughts on behavior.

Decision-making ability, psychopathology, and brain connectivity.

Decision-making is a cognitive process of central importance for the quality of our lives. Here, we ask whether a common factor underpins our diverse decision-making abilities. We obtained 32 decision-making measures from 830 young people and identified a common factor that we call "decision acuity," which was distinct from IQ and reflected a generic decision-making ability. Decision acuity was decreased in those with aberrant thinking and low general social functioning. Crucially, decision acuity and IQ had dissociable brain signatures, in terms of their associated neural networks of resting-state functional connectivity. Decision acuity was reliably measured, and its relationship with functional connectivity was also stable when measured in the same individuals 18 months later. Thus, our behavioral and brain data identify a new cognitive construct that underpins decision-making ability across multiple domains. This construct may be important for understanding mental health, particularly regarding poor social function and aberrant thought patterns.

Multi-Round Trust Game Quantifies Inter-Individual Differences in Social Exchange from Adolescence to Adulthood.

Investing in strangers in a socio-economic exchange is risky, as we may be uncertain whether they will reciprocate. Nevertheless, the potential rewards for cooperating can be great. Here, we used a cross sectional sample (n = 784) to study how the challenges of cooperation versus defection are negotiated across an important period of the lifespan: from adolescence to young adulthood (ages 14 to 25). We quantified social behaviour using a multi round investor-trustee task, phenotyping individuals using a validated model whose parameters characterise patterns of real exchange and constitute latent social characteristics. We found highly significant differences in investment behaviour according to age, sex, socio-economic status and IQ. Consistent with the literature, we showed an overall trend towards higher trust from adolescence to young adulthood but, in a novel finding, we characterized key cognitive mechanisms explaining this, especially regarding socio-economic risk aversion. Males showed lower risk-aversion, associated with greater investments. We also found that inequality aversion was higher in females and, in a novel relation, that socio-economic deprivation was associated with more risk averse play.

Children perform extensive information gathering when it is not costly.

Humans often face decisions where little is known about the choice options. Gathering information prior to making a choice is an important strategy to improve decision making under uncertainty. This is of particular importance during childhood and adolescence, when knowledge about the world is still limited. To examine how much information youths gather, we asked 107 children (8-9 years, N = 30), early (12-13 years, N = 41) and late adolescents (16-17 years, N = 36) to perform an information sampling task. We find that children gather significantly more information before making a decision compared to adolescents, but only if it does not come with explicit costs. Using computational modelling, we find that this is because children have reduced subjective costs for gathering information. Our findings thus demonstrate how children overcome their limited knowledge and neurocognitive constraints by deploying excessive information gathering, a developmental feature that could inform aberrant information gathering in psychiatric disorders.

Reduction in social learning and increased policy uncertainty about harmful intent is associated with pre-existing paranoid beliefs: Evidence from modelling a modified serial dictator game.

Current computational models suggest that paranoia may be explained by stronger higher-order beliefs about others and increased sensitivity to environments. However, it is unclear whether this applies to social contexts, and whether it is specific to harmful intent attributions, the live expression of paranoia. We sought to fill this gap by fitting a computational model to data (n = 1754) from a modified serial dictator game, to explore whether pre-existing paranoia could be accounted by specific alterations to cognitive parameters characterising harmful intent attributions. We constructed a 'Bayesian brain' model of others' intent, which we fitted to harmful intent and self-interest attributions made over 18 trials, across three different partners. We found that pre-existing paranoia was associated with greater uncertainty about other's actions. It moderated the relationship between learning rates and harmful intent attributions, making harmful intent attributions less reliant on prior interactions. Overall, the magnitude of harmful intent attributions was directly related to their uncertainty, and importantly, the opposite was true for self-interest attributions. Our results explain how pre-existing paranoia may be the result of an increased need to attend to immediate experiences in determining intentional threat, at the expense of what is already known, and more broadly, they suggest that environments that induce greater probabilities of harmful intent attributions may also induce states of uncertainty, potentially as an adaptive mechanism to better detect threatening others. Importantly, we suggest that if paranoia were able to be explained exclusively by core domain-general alterations we would not observe differential parameter estimates underlying harmful-intent and self-interest attributions.