Computational Psychiatry Research Articles

Computational mechanisms underlying illusion of control in delusional individuals

Humans navigate complex situations that require the accurate estimation of the controllability of the environment. Aberrant controllability computation might lead to maladaptive behaviors and poor mental health outcomes. Illusion of control, which refers to a heightened sense of control while the environment is uncontrollable, is one such manifestation and has been conceptually associated with delusional ideation. Nevertheless, this association has not yet been formally characterized in a computational framework. To address this, we used a computational psychiatry approach to quantify illusion of control in human participants with high (n = 125) or low (n = 126) trait delusion. Participants played a two-party exchange game in which their choices either did (“Controllable condition”) or did not (“Uncontrollable condition”) influence the future monetary offers made by simulated partners. We found that the two groups behaved similarly in model-agnostic measures (i.e., offer size, rejection rate). However, computational modeling revealed that compared to the low trait delusion group, the high delusion group overestimated their influence (“expected influence” parameter) over the offers made by their partners under the Uncontrollable condition. Highly delusional individuals also reported a stronger sense of control than those with low trait delusion in the Uncontrollable condition. Furthermore, the expected influence parameter and self-reported beliefs about controllability were significantly correlated in the Controllable condition in individuals with low trait delusion, whereas this relationship was diminished in those with high trait delusion. Collectively, these findings demonstrate that delusional ideation is associated with aberrant computation of and belief about environmental controllability, as well as a belief-behavior disconnect.

Is there mathematics to madness?

It’s hard to understand how heart failure can cause shortness of breath without some understanding of the role a pump plays in maintaining pressure gradients. The brain performs functions which are of a computational nature. Hence, a computational approach is likely necessary if we are to deeply understand disorders of brain function—particularly psychiatric disorders, where biological disturbances can be very subtle. More broadly, an understanding of the functions of an organ is critical if we are to comprehend the symptoms arising from disease in that organ. Computational psychiatry is a young field that attempts to harness the advances in computational progress for improved understanding, prognosis and treatment of mental illness. It lies at the interface of psychiatry, experimental and clinical psychology, neuroscience, machine learning, artificial intelligence and computational neuroscience.1 Computational psychiatry broadly encompasses two types of approaches. Data-driven approaches harness the advances in artificial intelligence, computational resources and big datasets. The theoretical branch, on the other hand, attempts to build mathematical or computational models of the relevant neural, circuit or cognitive processes.2

The Proposition for Bipolar Depression Forecasting Based on Wearable Data Collection.

Bipolar depression is treated wrongly as unipolar depression, on average, for 8 years. It is shown that this mismedication affects the occurrence of a manic episode and aggravates the overall condition of patients with bipolar depression. Significant effort was invested in early detection of depression and forecasting of responses to certain therapeutic approaches using a combination of features extracted from standard and online testing, wearables monitoring, and machine learning. In the case of unipolar depression, this approach yielded evidence that this data-based computational psychiatry approach would be helpful in clinical practice. Following a similar pipeline, we examined the usefulness of this approach to foresee a manic episode in bipolar depression, so that clinicians and family of the patient can help patient navigate through the time of crisis. Our projects combined the results from self-reported daily questionnaires, the data obtained from smart watches, and the data from regular reports from standard psychiatric interviews to feed various machine learning models to predict a crisis in bipolar depression. Contrary to satisfactory predictions in unipolar depression, we found that bipolar depression, having more complex dynamics, requires personalized approach. A previous work on physiological complexity (complex variability) suggests that an inclusion of electrophysiological data, properly quantified, might lead to better solutions, as shown in other projects of our group concerning unipolar depression. Here, we make a comparison of previously performed research in a methodological sense, revisiting and additionally interpreting our own results showing that the methodological approach to mania forecasting may be modified to provide an accurate prediction in bipolar depression.

On the Importance of Being Flexible: Dynamic Brain Networks and Their Potential Functional Significances.

In this theoretical review, we begin by discussing brains and minds from a dynamical systems perspective, and then go on to describe methods for characterizing the flexibility of dynamic networks. We discuss how varying degrees and kinds of flexibility may be adaptive (or maladaptive) in different contexts, specifically focusing on measures related to either more disjoint or cohesive dynamics. While disjointed flexibility may be useful for assessing neural entropy, cohesive flexibility may potentially serve as a proxy for self-organized criticality as a fundamental property enabling adaptive behavior in complex systems. Particular attention is given to recent studies in which flexibility methods have been used to investigate neurological and cognitive maturation, as well as the breakdown of conscious processing under varying levels of anesthesia. We further discuss how these findings and methods might be contextualized within the Free Energy Principle with respect to the fundamentals of brain organization and biological functioning more generally, and describe potential methodological advances from this paradigm. Finally, with relevance to computational psychiatry, we propose a research program for obtaining a better understanding of ways that dynamic networks may relate to different forms of psychological flexibility, which may be the single most important factor for ensuring human flourishing.

Cognitive [Computational] Neuroscience Test Reliability and Clinical Applications for Serious Mental Illness (CNTRaCS) Consortium: Progress and Future Directions.

The development of treatments for impaired cognition in schizophrenia has been characterized as the most important challenge facing psychiatry at the beginning of the twenty-first century. The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) project was designed to build on the potential benefits of using tasks and tools from cognitive neuroscience to better understanding and treat cognitive impairments in psychosis. These benefits include: (1) the use of fine-grained tasks that measure discrete cognitive processes; (2) the ability to design tasks that distinguish between specific cognitive domain deficits and poor performance due to generalized deficits resulting from sedation, low motivation, poor test taking skills, etc.; and (3) the ability to link cognitive deficits to specific neural systems, using animal models, neuropsychology, and functional imaging. CNTRICS convened a series of meetings to identify paradigms from cognitive neuroscience that maximize these benefits and identified the steps need for translation into use in clinical populations. The Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRaCS) Consortium was developed to help carry out these steps. CNTRaCS consists of investigators at five different sites across the country with diverse expertise relevant to a wide range of the cognitive systems identified as critical as part of CNTRICs. This work reports on the progress and current directions in the evaluation and optimization carried out by CNTRaCS of the tasks identified as part of the original CNTRICs process, as well as subsequent extensions into the Positive Valence systems domain of Research Domain Criteria (RDoC). We also describe the current focus of CNTRaCS, which involves taking a computational psychiatry approach to measuring cognitive and motivational function across the spectrum of psychosis. Specifically, the current iteration of CNTRaCS is using computational modeling to isolate parameters reflecting potentially more specific cognitive and visual processes that may provide greater interpretability in understanding shared and distinct impairments across psychiatric disorders.

Modeling of placebo effect in stochastic reward tasks by reinforcement learning

Several studies in the field of computational psychiatry focus on modeling diseases using reinforcement learning. This study aims to model through reinforcement learning using real data of stochastic reward with regards to the placebo effect. More specifically, we model the placebo effect using real data related to the non-invasive brain stimulation technique. In contrast to human data, the results of the machine learning approach showed no difference owing to the differences in the placebo effect.

Peril, prudence and planning as risk, avoidance and worry

Risk occupies a central role in both the theory and practice of decision-making. Although it is deeply implicated in many conditions involving dysfunctional behavior and thought, modern theoretical approaches to understanding and mitigating risk, in either one-shot or sequential settings, have yet to permeate fully the fields of neural reinforcement learning and computational psychiatry. Here we use one prominent approach, called conditional value-at-risk (CVaR), to examine optimal risk-sensitive choice and a form of optimal, risk-sensitive offline planning. We relate the former to both a justified form of the gambler’s fallacy and extremely risk-avoidant behavior resembling that observed in anxiety disorders. We relate the latter to worry and rumination.

AI ethics in computational psychiatry: From the neuroscience of consciousness to the ethics of consciousness

Methods used in artificial intelligence (AI) overlap with methods used in computational psychiatry (CP). Hence, considerations from AI ethics are also relevant to ethical discussions of CP. Ethical issues include, among others, fairness and data ownership and protection. Apart from this, morally relevant issues also include potential transformative effects of applications of AI—for instance, with respect to how we conceive of autonomy and privacy. Similarly, successful applications of CP may have transformative effects on how we categorise and classify mental disorders and mental health. Since many mental disorders go along with disturbed conscious experiences, it is desirable that successful applications of CP improve our understanding of disorders involving disruptions in conscious experience. Here, we discuss prospects and pitfalls of transformative effects that CP may have on our understanding of mental disorders. In particular, we examine the concern that even successful applications of CP may fail to take all aspects of disordered conscious experiences into account.

Computational Psychiatry Across Species to Study the Biology of Hallucinations

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Regenerative Virtual Therapy: The Use of Multisensory Technologies and Mindful Attention for Updating the Altered Representations of the Bodily Self.

The term “regenerative medicine” (RM) indicates an emerging trend in biomedical sciences that aims at replacing, engineering, or regenerating human cells, tissues, or organs to restore or establish normal function. So far, the focus of RM has been the physical body. Neuroscience, however, is now suggesting that mental disorders can be broadly characterized by a dysfunction in the way the brain computes and integrates the representations of the inner and outer body across time [bodily self-consciousness (BSC)]. In this perspective, we proposed a new kind of clinical intervention, i.e., “Regenerative Virtual Therapy” (RVT), which integrates knowledge from different disciplines, from neuroscience to computational psychiatry, to regenerate a distorted or faulty BSC. The main goal of RVT was to use technology-based somatic modification techniques to restructure the maladaptive bodily representations behind a pathological condition. Specifically, starting from a Bayesian model of our BSC (i.e., body matrix), we suggested the use of mindful attention, cognitive reappraisal, and brain stimulation techniques merged with high-rewarding and novel synthetic multisensory bodily experience (i.e., a virtual reality full-body illusion in sync with a low predictabIlity interoceptive modulation) to rewrite a faulty experience of the body and to regenerate the wellbeing of an individual. The use of RVT will also offer an unprecedented experimental overview of the dynamics of our bodily representations, allowing the reverse-engineering of their functioning for hacking them using advanced technologies.

Computational Predictions for OCD Pathophysiology and Treatment: A Review.

Obsessive compulsive disorder (OCD) can manifest as a debilitating disease with high degrees of co-morbidity as well as clinical and etiological heterogenity. However, the underlying pathophysiology is not clearly understood. Computational psychiatry is an emerging field in which behavior and its neural correlates are quantitatively analyzed and computational models are developed to improve understanding of disorders by comparing model predictions to observations. The aim is to more precisely understand psychiatric illnesses. Such computational and theoretical approaches may also enable more personalized treatments. Yet, these methodological approaches are not self-evident for clinicians with a traditional medical background. In this mini-review, we summarize a selection of computational OCD models and computational analysis frameworks, while also considering the model predictions from a perspective of possible personalized treatment. The reviewed computational approaches used dynamical systems frameworks or machine learning methods for modeling, analyzing and classifying patient data. Bayesian interpretations of probability for model selection were also included. The computational dissection of the underlying pathology is expected to narrow the explanatory gap between the phenomenological nosology and the neuropathophysiological background of this heterogeneous disorder. It may also contribute to develop biologically grounded and more informed dimensional taxonomies of psychopathology.

More by stick than by carrot: A reinforcement learning style rooted in the medial frontal cortex in anorexia nervosa.

Anorexia nervosa (AN) is characterized by a relentless pursuit of thinness, despite serious implications for health and social relations. In a previous study wielding the power of computational psychiatry, we found alterations in learning from negative feedback and in neural activity in the posterior medial frontal cortex (pMFC) in young acutely underweight AN patients (acAN). Here we ask whether these abnormalities are merely a state-related consequence of the illness or whether they might constitute a trait marker predisposing individuals to AN. To address this question, we employed the same reinforcement learning paradigm during fMRI with 31 female former AN patients after complete weight-recovery (recAN) and 31 age-matched healthy volunteers (15-28 years). Participants performed a decision task that required adaptation to changing reward contingencies. Data were analyzed within a hierarchical Gaussian filter model, which captures interindividual variability in feedback learning and decision-making under uncertainty. Similar to acute patients, individuals recovered from AN appear to emphasize negative over positive feedback when updating expectations regarding changing reward-punishment contingencies (difference in learning rate between punished and rewarded trials was increased in recAN: p = .006, d = .70. This behavioral pattern was mirrored in hyperactivation of the pMFC following negative feedback (FWE p < .001). Because the previously observed alterations in acANs are also evident after recovery and do not correlate with state variables like weight, altered feedback learning might be a trait marker of AN. The neural underpinnings of these alterations may lie in the pMFC. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

RECENT WORK WITH CONTEMPORARY COMPUTATIONAL METHODS AND ARTIFICIAL INTELLIGENCE TO ADVANCE THE PRACTICE OF CHILD AND ADOLESCENT PSYCHIATRY

This Symposium will provide a data-driven primer of computational psychiatry for child and adolescent psychiatrists. An intramural NIMH scientist will provide an overview of computational psychiatry. Two experts on Bayesian statistical approaches will introduce Bayesian statistics. These experts will review recent published and unpublished examples examining data sets from large clinical trials. A computer science engineer focused on psychiatric studies will provide a clinically meaningful overview of artificial intelligence methodology. This presenter will review the recent published and unpublished studies with probabilistic graphical models with symptom profiles and thresholds of change for the prediction of antidepressant response in clinical practice. An expert in clinical pharmacology will lead an interactive discussion with the panel and participants. Bayesian hierarchical modeling facilitates greater precision in the estimation of treatment effects, has less restrictive assumptions compared to prior approaches, provides models that have enhanced clinical utility, and integrates multilevel data. One recent example demonstrated that in adolescents who are not receiving CBT and have depressive symptoms that did not respond to an SSRI, a second trial of an SSRI provided increased improvement in depressive symptoms in a briefer time period compared to venlafaxine. Other analyses demonstrated that in children and adolescents with OCD and anxiety, SSRIs had distinct side effects compared to placebo and SNRIs. Recent work with probabilistic graphical models demonstrated that variation in distinct depressive symptoms assessed with the Children’s Depression Rating Scale-Revised (CDRS-R) predicted outcomes from treatment with fluoxetine and duloxetine with 73% to 77% accuracy. Contemporary computational approaches have the prospect of advancing the clinical practice of child and adolescent psychiatry. Bayesian hierarchical modeling has advanced the understanding of existing data sets. Probabilistic graphical models provided clinically meaningful predictions in samples of depressed adolescents treated with fluoxetine, duloxetine, and placebo.

Natural and Artificial Intelligence: A brief introduction to the interplay between AI and neuroscience research

Neuroscience and artificial intelligence (AI) share a long history of collaboration. Advances in neuroscience, alongside huge leaps in computer processing power over the last few decades, have given rise to a new generation of in silico neural networks inspired by the architecture of the brain. These AI systems are now capable of many of the advanced perceptual and cognitive abilities of biological systems, including object recognition and decision making. Moreover, AI is now increasingly being employed as a tool for neuroscience research and is transforming our understanding of brain functions. In particular, deep learning has been used to model how convolutional layers and recurrent connections in the brain’s cerebral cortex control important functions, including visual processing, memory, and motor control. Excitingly, the use of neuroscience-inspired AI also holds great promise for understanding how changes in brain networks result in psychopathologies, and could even be utilized in treatment regimes. Here we discuss recent advancements in four areas in which the relationship between neuroscience and AI has led to major advancements in the field; (1) AI models of working memory, (2) AI visual processing, (3) AI analysis of big neuroscience datasets, and (4) computational psychiatry.

Computational Psychiatry Needs Time and Context.

Why has computational psychiatry yet to influence routine clinical practice? One reason may be that it has neglected context and temporal dynamics in the models of certain mental health problems. We develop three heuristics for estimating whether time and context are important to a mental health problem: Is it characterized by a core neurobiological mechanism? Does it follow a straightforward natural trajectory? And is intentional mental content peripheral to the problem? For many problems the answers are no, suggesting that modeling time and context is critical. We review computational psychiatry advances toward this end, including modeling state variation, using domain-specific stimuli, and interpreting differences in context. We discuss complementary network and complex systems approaches. Novel methods and unification with adjacent fields may inspire a new generation of computational psychiatry.

Reward learning and working memory: Effects of massed versus spaced training and post-learning delay period

Neuroscience research has illuminated the mechanisms supporting learning from reward feedback, demonstrating a critical role for the striatum and midbrain dopamine system. However, in humans, short-term working memory that is dependent on frontal and parietal cortices can also play an important role, particularly in commonly used paradigms in which learning is relatively condensed in time. Given the growing use of reward-based learning tasks in translational studies in computational psychiatry, it is important to understand the extent of the influence of working memory and also how core gradual learning mechanisms can be better isolated. In our experiments, we manipulated the spacing between repetitions along with a post-learning delay preceding a test phase. We found that learning was slower for stimuli repeated after a long delay (spaced-trained) compared to those repeated immediately (massed-trained), likely reflecting the remaining contribution of feedback learning mechanisms when working memory is not available. For massed learning, brief interruptions led to drops in subsequent performance, and individual differences in working memory capacity positively correlated with overall performance. Interestingly, when tested after a delay period but not immediately, relative preferences decayed in the massed condition and increased in the spaced condition. Our results provide additional support for a large role of working memory in reward-based learning in temporally condensed designs. We suggest that spacing training within or between sessions is a promising approach to better isolate and understand mechanisms supporting gradual reward-based learning, with particular importance for understanding potential learning dysfunctions in addiction and psychiatric disorders.

Technical note: A fast and robust integrator of delay differential equations in DCM for electrophysiological data

Dynamic causal models (DCMs) of electrophysiological data allow, in principle, for inference on hidden, bulk synaptic function in neural circuits. The directed influences between the neuronal elements of modeled circuits are subject to delays due to the finite transmission speed of axonal connections. Ordinary differential equations are therefore not adequate to capture the ensuing circuit dynamics, and delay differential equations (DDEs) are required instead. Previous work has illustrated that the integration of DDEs in DCMs benefits from sophisticated integration schemes in order to ensure rigorous parameter estimation and correct model identification. However, integration schemes that have been proposed for DCMs either emphasize speed (at the possible expense of accuracy) or robustness (but with computational costs that are problematic in practice).In this technical note, we propose an alternative integration scheme that overcomes these shortcomings and offers high computational efficiency while correctly preserving the nature of delayed effects. This integration scheme is available as open-source code in the Translational Algorithms for Psychiatry-Advancing Science (TAPAS) toolbox and can be easily integrated into existing software (SPM) for the analysis of DCMs for electrophysiological data. While this paper focuses on its application to the convolution-based formalism of DCMs, the new integration scheme can be equally applied to more advanced formulations of DCMs (e.g. conductance based models). Our method provides a new option for electrophysiological DCMs that offers the speed required for scientific projects, but also the accuracy required for rigorous translational applications, e.g. in computational psychiatry.

Precision and the Bayesian brain

Scientific thinking about the minds of humans and other animals has been transformed by the idea that the brain is Bayesian. A cornerstone of this idea is that agents set the balance between prior knowledge and incoming evidence based on how reliable or 'precise' these different sources of information are - lending the most weight to that which is most reliable. This concept of precision has crept into several branches of cognitive science and is a lynchpin of emerging ideas in computational psychiatry - where unusual beliefs or experiences are explained as abnormalities in how the brain estimates precision. But what precisely is precision? In this Primer we explain how precision has found its way into classic and contemporary models of perception, learning, self-awareness, and social interaction. We also chart how ideas around precision are beginning to change in radical ways, meaning we must get more precise about how precision works.

Consciousness in active inference: Deep self-models, other minds, and the challenge of psychedelic-induced ego-dissolution.

Predictive processing approaches to brain function are increasingly delivering promise for illuminating the computational underpinnings of a wide range of phenomenological states. It remains unclear, however, whether predictive processing is equipped to accommodate a theory of consciousness itself. Furthermore, objectors have argued that without specification of the core computational mechanisms of consciousness, predictive processing is unable to inform the attribution of consciousness to other non-human (biological and artificial) systems. In this paper, I argue that an account of consciousness in the predictive brain is within reach via recent accounts of phenomenal self-modelling in the active inference framework. The central claim here is that phenomenal consciousness is underpinned by ‘subjective valuation’—a deep inference about the precision or ‘predictability’ of the self-evidencing (‘fitness-promoting’) outcomes of action. Based on this account, I argue that this approach can critically inform the distribution of experience in other systems, paying particular attention to the complex sensory attenuation mechanisms associated with deep self-models. I then consider an objection to the account: several recent papers argue that theories of consciousness that invoke self-consciousness as constitutive or necessary for consciousness are undermined by states (or traits) of ‘selflessness’; in particular the ‘totally selfless’ states of ego-dissolution occasioned by psychedelic drugs. Drawing on existing work that accounts for psychedelic-induced ego-dissolution in the active inference framework, I argue that these states do not threaten to undermine an active inference theory of consciousness. Instead, these accounts corroborate the view that subjective valuation is the constitutive facet of experience, and they highlight the potential of psychedelic research to inform consciousness science, computational psychiatry and computational phenomenology.

Increased and biased deliberation in social anxiety.

A goal of computational psychiatry is to ground symptoms in basic mechanisms. Theory suggests that avoidance in anxiety disorders may reflect dysregulated mental simulation, a process for evaluating candidate actions. If so, these covert processes should have observable consequences: choices reflecting increased and biased deliberation. In two online general population samples, we examined how self-report symptoms of social anxiety disorder predict choices in a socially framed reinforcement learning task, the patent race, in which the pattern of choices reflects the content of deliberation. Using a computational model to assess learning strategy, we found that self-report social anxiety was indeed associated with increased deliberative evaluation. This effect was stronger for a particular subset of feedback ('upward counterfactual') in one of the experiments, broadly matching the biased content of rumination in social anxiety disorder, and robust to controlling for other psychiatric symptoms. These results suggest a grounding of symptoms of social anxiety disorder in more basic neuro-computational mechanisms.