Towards a computational psychiatry of juvenile obsessive-compulsive disorder

Obsessive-Compulsive Disorder (OCD) most often emerges during adolescence, but we know little about the aberrant neural and cognitive developmental mechanisms that underlie its emergence during this critical developmental period. To move towards a computational psychiatry of juvenile OCD, we review studies on the computational, neuropsychological and neural alterations in juvenile OCD and link these findings to the adult OCD and cognitive neuroscience literature. We find consistent difficulties in tasks entailing complex decision making and set shifting, but limited evidence in other areas that are altered in adult OCD, such as habit and confidence formation. Based on these findings, we establish a neurocomputational framework that illustrates how cognition can go awry and lead to symptoms of juvenile OCD. We link these possible aberrant neural processes to neuroimaging findings in juvenile OCD and show that juvenile OCD is mainly characterised by disruptions of complex reasoning systems

Increased decision thresholds trigger extended information gathering across the compulsivity spectrum

Indecisiveness and doubt are cognitive phenotypes of compulsive disorders, including obsessive-compulsive disorder. Little is known regarding the cognitive mechanisms that drive these behaviours across a compulsivity spectrum. Here, we used a sequential information gathering task to study indecisiveness in subjects with high and low obsessive-compulsive scores. These subjects were selected from a large population-representative database, and matched for intellectual and psychiatric factors. We show that high compulsive subjects sampled more information and performed better when sampling was cost-free. When sampling was costly, both groups adapted flexibly to reduce their information gathering. Computational modelling revealed that increased information gathering behaviour could be explained by higher decision thresholds that, in turn, were driven by a delayed emergence of impatience or urgency. Our findings show that indecisiveness generalises to a compulsivity spectrum beyond frank clinical disorder, and this behaviour can be explained within a decision-theoretic framework as arising from an augmented decision threshold associated with an attenuated urgency signal

Avoid jumping to conclusions under uncertainty in Obsessive Compulsive Disorder.

High levels of intolerance of uncertainty (IU) could contribute to abnormal decision making in uncertain situations. Patients with Obsessive Compulsive Disorder (OCD) often report high IU, indecisiveness and the need to seek greater certainty before making decisions. The Beads task is a commonly used task assessing the degree of information gathering prior to making a decision and so would be predicted to show impairments in OCD patients. Results to date have found mixed support for this, possibility due to methodological issues. Here, a group of OCD patients (n = 50) with no comorbidities was compared with age, gender, and verbal-IQ matched controls (n = 50) on the most commonly used version of the Beads task. An independent sample of healthy volunteers with high versus low OC symptoms, and high versus low IU were also assessed (n = 125). There was no evidence that patients with OCD differed from control volunteers in the degree of information gathering prior to making a decision. Medication status and age did not appear to mediate performance. Similarly, there were no association in healthy volunteers between task performance and OC or IU characteristics. Additional measures examining the degree of certainty initially showed support for greater uncertainty in patients, but this was due to deviations from task instructions in a subset of patients. We conclude that despite the large sample size and good matching between groups, the Beads task in its most widely used form is not a useful measure of IU or of information gathering in OCD. The results argue against a robust behavioural difference in OCD when compared to controls. Recommendations for future studies employing the task are discussed

Metacognitive impairments extend perceptual decision making weaknesses in compulsivity.

Awareness of one's own abilities is of paramount importance in adaptive decision making. Psychotherapeutic theories assume such metacognitive insight is impaired in compulsivity, though this is supported by scant empirical evidence. In this study, we investigate metacognitive abilities in compulsive participants using computational models, where these enable a segregation between metacognitive and perceptual decision making impairments. We examined twenty low-compulsive and twenty high-compulsive participants, recruited from a large population-based sample, and matched for other psychiatric and cognitive dimensions. Hierarchical computational modelling of the participants' metacognitive abilities on a visual global motion detection paradigm revealed that high-compulsive participants had a reduced metacognitive ability. This impairment was accompanied by a perceptual decision making deficit whereby motion-related evidence was accumulated more slowly in high compulsive participants. Our study shows that the compulsivity spectrum is associated with a reduced ability to monitor one's own performance, over and above any perceptual decision making difficulties

Boosting Serotonin Increases Information Gathering by Reducing Subjective Cognitive Costs

Serotonin is implicated in the valuation of aversive costs, such as delay or physical effort. However, its role in governing sensitivity to cognitive effort, for example, deliberation costs during information gathering, is unclear. We show that treatment with a serotonergic antidepressant in healthy human individuals of either sex enhances a willingness to gather information when trying to maximize reward. Using computational modeling, we show this arises from a diminished sensitivity to subjective deliberation costs during the sampling process. This result is consistent with the notion that serotonin alleviates sensitivity to aversive costs in a domain-general fashion, with implications for its potential contribution to a positive impact on motivational deficits in psychiatric disorders.SIGNIFICANCE STATEMENT Gathering information about the world is essential for successfully navigating it. However, sampling information is costly, and we need to balance between gathering too little and too much information. The neurocomputational mechanisms underlying this arbitration between a putative gain, such as reward, and the associated costs, such as allocation of cognitive resources, remain unclear. In this study, we show that week-long daily treatment with a serotonergic antidepressant enhances a willingness to gather information when trying to maximize reward. Computational modeling indicates this arises from a reduced perception of aversive costs, rendering information gathering less cognitively effortful. This finding points to a candidate mechanism by which serotonergic treatment might help alleviate motivational deficits in a range of mental illnesses

Neurocognitive Mechanisms of Learning and Decision-Making in Adolescent-OCD: A Computational Approach

Early-onset obsessive-compulsive disorder (OCD) is substantially less researched than adult-OCD, resulting in prevalent equivocation surrounding the neurocognitive profile of child-OCD. Research into this area is pivotal as population studies report that youths with OCD struggle significantly in academic settings. In the General Introduction of this thesis, I reviewed existing literature and found that strikingly, young patients do not show impairment on features that are considered both hallmarks of adult OCD and tightly linked to disorder symptomatology, such as response inhibition and cognitive flexibility. Among the characteristics that are thought to be present in children and adolescents with OCD are abnormal decision-making under uncertainty and impaired learning, and I decided to focus on these features as they may be driving poor academic attainment in young people with the disorder. In addition, I sought to investigate other cognitive processes that have not been well-researched in adolescent-OCD but are found to be robustly altered in adult OCD such as goal directed/model-based reasoning, meta-cognition, and feedback sensitivity. I aimed to delineate these various processes using a battery of suitably complex cognitive tasks. Moreover, I highlighted that majority of past studies fail to find differences between young patients and controls due to behavioural signatures being too subtle to be uncovered by standard statistical analyses. Hence, I employed computational modelling of cognitive task data to disentangle latent decision-making processes displayed by adolescents with OCD. In Chapter 2, I modelled data from the Wisconsin Card Sorting task, a frequently used paradigm of cognitive flexibility, and confirmed that youths with OCD show equivalent performance on the task to controls. Only patients on serotonergic medication showed increased response latencies and a tendency to make unique errors (choosing a deck associated with no rule present on the test card). Next, in Chapter 3, I sought to understand instrumental and Pavlovian learning, and whether adolescents with OCD show increased punishment sensitivity on a novel aversive Pavlovian-to Instrumental Transfer paradigm. Once again, patient performance was equivalent to that of controls. Hence, the remaining chapters were dedicated to probing behaviour on probabilistic paradigms. In Chapter 4, I formally investigated model-based and model-free learning using a well-validated two step decision-making task, and fit a reinforcement learning drift diffusion model to both choice and reaction time data. Patients showed increased exploration on the task as well as faster and more erratic decisions compared to controls. Nonetheless, model-based learning was equivalent between groups. In the penultimate chapter, I demonstrate on a predictive-inference task that patients with OCD update their choices more frequently compared to controls independent of prediction error magnitude. Finally, in Chapter 6, I administered a probabilistic reversal learning paradigm to a large sample of 50 adolescent patients and 53 matched controls. Standard analyses revealed a significant reversal learning deficit in patients with OCD, wherein they displayed more errors and a lower propensity to repeat choices following positive feedback during the post-reversal phase. Crucially, computational modelling revealed striking group differences where adolescents with OCD displayed elevated reward learning and lower punishment learning, increased exploration, and decreased perseveration compared to controls. In the General Discussion, I emphasise that atypical learning and decision-making in adolescent-OCD are more pronounced on probabilistic tasks, where task environments are more volatile. Results are partly discussed in the context of the uncertainty model of OCD, where subjective feelings of doubt experienced by patients drive compulsive behaviours such as checking and certainty-seeking in daily life, alongside excessive exploration on probabilistic tasks. I also consider various explanations for cognitive distinctions between adult- and adolescent OCD. More general implications of the findings are discussed for understanding OCD in the context of adolescent development and for treatment/support strategies.WELLCOME TRUST (104631/Z/14/Z

Atypical action updating in a dynamic environment associated with adolescent obsessive-compulsive disorder

Background: Computational research had determined that adults with obsessive–compulsive disorder (OCD) display heightened action updating in response to noise in the environment and neglect metacognitive information (such as confidence) when making decisions. These features are proposed to underlie patients’ compulsions despite the knowledge they are irrational. Nonetheless, it is unclear whether this extends to adolescents with OCD as research in this population is lacking. Thus, this study aimed to investigate the interplay between action and confidence in adolescents with OCD. Methods: Twenty-seven adolescents with OCD and 46 controls completed a predictive-inference task, designed to probe how subjects’ actions and confidence ratings fluctuate in response to unexpected outcomes. We investigated how subjects update actions in response to prediction errors (indexing mismatches between expectations and outcomes) and used parameters from a Bayesian model to predict how confidence and action evolve over time. Confidence–action association strength was assessed using a regression model. We also investigated the effects of serotonergic medication. Results: Adolescents with OCD showed significantly increased learning rates, particularly following small prediction errors. Results were driven primarily by unmedicated patients. Confidence ratings appeared equivalent between groups, although model-based analysis revealed that patients’ confidence was less affected by prediction errors compared to controls. Patients and controls did not differ in the extent to which they updated actions and confidence in tandem. Conclusions: Adolescents with OCD showed enhanced action adjustments, especially in the face of small prediction errors, consistent with previous research establishing ‘just-right’ compulsions, enhanced error-related negativity, and greater decision uncertainty in paediatric-OCD. These tendencies were ameliorated in patients receiving serotonergic medication, emphasising the importance of early intervention in preventing disorder-related cognitive deficits. Confidence ratings were equivalent between young patients and controls, mirroring findings in adult OCD research

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

Selective effects of serotonin on choices to gather more information

Background: Gathering and evaluating information leads to better decisions, but often at cost. The balance between information seeking and exploitation features in neurodevelopmental, mood, psychotic and substance-related disorders. Serotonin’s role has been highlighted by experimental reduction of its precursor, tryptophan. Aims: We tested the boundaries and applicability of this role by asking whether changes to information sampling would be observed following acute doses of serotonergic and catecholaminergic clinical treatments. We used a variant of the Information Sampling Task (IST) to measure how much information a person requires before they make a decision. This task allows participants to sample information until satisfied to make a choice. Methods: In separate double-blind placebo-controlled experiments, we tested 27 healthy participants on/off 20 mg of the serotonin reuptake inhibitor (SRI) citalopram, and 22 participants on/off 40 mg of the noradrenergic reuptake inhibitor atomoxetine. The IST variant minimised effects of temporal impulsivity and loss aversion. Analyses used a variety of participant prior expectations of sampling spaces in the IST, including a new prior that accounts for learning of likely states across trials. We analysed behaviour by a new method that also accounts for baseline individual differences of risk preference. Results: Baseline preferences demonstrated risk aversion. Citalopram decreased the expected utility of choices and probability of being correct based on informational content of samples collected, suggesting participants collected less useful information before making a choice. Atomoxetine did not influence information seeking. Conclusion: Acute changes of serotonin activity by way of a single SRI dose alter information-seeking behaviour