Computational Psychiatry Research Articles

109. The Challenges of Measuring Individual Differences in Computational Psychiatry

109. The Challenges of Measuring Individual Differences in Computational Psychiatry

Computational psychiatry and the psychopathology of psychosis: Promising leads and blind alleys.

Computational psychiatry and the psychopathology of psychosis: Promising leads and blind alleys.

Speech graph analysis in obsessive-compulsive disorder: The relevance of dream reports

Obsessive-compulsive disorder (OCD) is a distressing disorder characterized by the presence of intrusive thoughts, images or urges (obsessions) and/or behavioral efforts to reduce the anxiety (compulsions). OCD lifetime prevalence varies between 1% and 3% in the general population and there are no reliable markers that support the diagnosis. In order to fill this gap, Computational Psychiatry employs multiple types of quantitative analyses to improve the understanding, diagnosis, prediction, and treatment of mental illnesses including OCD. One of these computational tools is speech graphs analysis. A graph represents a network of nodes connected by edges: in non-semantic speech graphs, nodes correspond to words and edges correspond to the directed link between consecutive words. Using non-semantic speech graphs, we compared free speech samples from OCD patients and healthy controls (HC), to test whether speech graphs analysis can grasp structural differences in speech between these groups. To this end, 39 OCD patients and 37 HC were interviewed and recorded during six types of speech reports: yesterday, dream, old memory, positive image, negative image and neutral image. Also, the Obsessive-Compulsive Inventory-Revised (OCI-R) and the Yale Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess symptom severity. The graph-theoretical structural analysis of dream reports showed that OCD patients have significantly smaller lexical diversity, lower speech connectedness and a higher recurrence of words in comparison with HC. The other five report types failed to show differences between the groups, adding to the notion that dream reports are especially informative of speech structure in different psychiatric states. Further investigation is necessary to completely assess the potential of this tool in OCD.

Stimulating human prefrontal cortex increases reward learning

Work in computational psychiatry suggests that mood disorders may stem from aberrant reinforcement learning processes. Specifically, it has been proposed that depressed individuals believe that negative events are more informative than positive events, resulting in higher learning rates from negative outcomes (Pulcu and Browning, 2019). In this proof-of-concept study, we investigated whether transcranial direct current stimulation (tDCS) applied to dorsolateral prefrontal cortex, as commonly used in depression treatment trials, might change learning rates for affective outcomes. Healthy adults completed an established reinforcement learning task (Pulcu and Browning, 2017) in which the information content of reward and loss outcomes was manipulated by varying the volatility of stimulus-outcome associations. Learning rates on the tasks were quantified using computational models. Stimulation over dorsolateral prefrontal cortex (DLPFC) but not motor cortex (M1) increased learning rates specifically for reward outcomes. The effects of prefrontal tDCS were cognitive state-dependent: tDCS applied during task performance increased learning rates for wins; tDCS applied before task performance decreased both win and loss learning rates. A replication study confirmed the key finding that tDCS to DLPFC during task performance increased learning rates specifically for rewards. Taken together, these findings demonstrate the potential of tDCS for modulating computational parameters of reinforcement learning that are relevant to mood disorders.

Can an algorithm become delusional? Evaluating ontological commitments and methodology of computational psychiatry

AbstractThe computational approach to psychiatric disorders, including delusions, promises explanation and treatment. Here, we argue that an information processing approach might be misleading to understand psychopathology and requires further refinement. We explore the claim of computational psychiatry being a bridge between phenomenology and physiology while focussing on the ontological commitments and corresponding methodology computational psychiatry is based on. Interconnecting ontological claims and methodological practices, the paper illustrates the structure of theory-building and testing in computational psychiatry.First, we will explain the ontological commitments computational psychiatry is grounded in, theBayesian Brain hypothesis(BBH) of unconscious inference, paired with normative deontic approaches applied to gauge psychopathology. We then turn to the steps taken in empirical paradigms, from definitions, which are used as starting points, to the operationalisation and isolation of cognitive processes and hypothesis testing based on algorithmic models, to consecutive interpretations regarding the aetiology of psychiatric disorders. We outline how experimental paradigms in computational psychiatry are specifically designed to confirm aberrations in assumed inferential processes, which are thought of as being the underlyingcore invariant features.We will illustrate a gap between the ontological commitments of computational psychiatry and the operationalisation and testing of the cognition assumed to be relevant for psychopathology. This conceptual gap is of utmost importance when designing computational paradigms and may impede a crisp understanding of the approach. Lastly, in evaluating the conceptual gap, it becomes apparent that the information processing formalism used in computational psychiatry is still grounded in rational cognitive psychology.

Reinforcement learning as an innovative model-based approach: Examples from precision dosing, digital health and computational psychiatry.

Model-based approaches are instrumental for successful drug development and use. Anchored within pharmacological principles, through mathematical modeling they contribute to the quantification of drug response variability and enables precision dosing. Reinforcement learning (RL)-a set of computational methods addressing optimization problems as a continuous learning process-shows relevance for precision dosing with high flexibility for dosing rule adaptation and for coping with high dimensional efficacy and/or safety markers, constituting a relevant approach to take advantage of data from digital health technologies. RL can also support contributions to the successful development of digital health applications, recognized as key players of the future healthcare systems, in particular for reducing the burden of non-communicable diseases to society. RL is also pivotal in computational psychiatry-a way to characterize mental dysfunctions in terms of aberrant brain computations-and represents an innovative modeling approach forpsychiatric indications such as depression or substance abuse disorders for which digital therapeutics are foreseen as promising modalities.

Restoring the missing person to personalized medicine and precision psychiatry.

Precision psychiatry has emerged as part of the shift to personalized medicine and builds on frameworks such as the U.S. National Institute of Mental Health Research Domain Criteria (RDoC), multilevel biological "omics" data and, most recently, computational psychiatry. The shift is prompted by the realization that a one-size-fits all approach is inadequate to guide clinical care because people differ in ways that are not captured by broad diagnostic categories. One of the first steps in developing this personalized approach to treatment was the use of genetic markers to guide pharmacotherapeutics based on predictions of pharmacological response or non-response, and the potential risk of adverse drug reactions. Advances in technology have made a greater degree of specificity or precision potentially more attainable. To date, however, the search for precision has largely focused on biological parameters. Psychiatric disorders involve multi-level dynamics that require measures of phenomenological, psychological, behavioral, social structural, and cultural dimensions. This points to the need to develop more fine-grained analyses of experience, self-construal, illness narratives, interpersonal interactional dynamics, and social contexts and determinants of health. In this paper, we review the limitations of precision psychiatry arguing that it cannot reach its goal if it does not include core elements of the processes that give rise to psychopathological states, which include the agency and experience of the person. Drawing from contemporary systems biology, social epidemiology, developmental psychology, and cognitive science, we propose a cultural-ecosocial approach to integrating precision psychiatry with person-centered care.

Understanding mental health through computers: An introduction to computational psychiatry.

Computational psychiatry recently established itself as a new tool in the study of mental disorders and problems. Integration of different levels of analysis is creating computational phenotypes with clinical and research values, and constructing a way to arrive at precision psychiatry are part of this new branch. It conceptualizes the brain as a computational organ that receives from the environment parameters to respond to challenges through calculations and algorithms in continuous feedback and feedforward loops with a permanent degree of uncertainty. Through this conception, one can seize an understanding of the cerebral and mental processes in the form of theories or hypotheses based on data. Using these approximations, a better understanding of the disorder and its different determinant factors facilitates the diagnostics and treatment by having an individual, ecologic, and holistic approach. It is a tool that can be used to homologate and integrate multiple sources of information given by several theoretical models. In conclusion, it helps psychiatry achieve precision and reproducibility, which can help the mental health field achieve significant advancement. This article is a narrative review of the basis of the functioning of computational psychiatry with a critical analysis of its concepts.

Interpersonal coordination in schizophrenia: a concise update on paradigms, computations, and neuroimaging findings.

Abstract Social functioning impairment is a hallmark of mental illness. As one of the most intractable and severe psychiatric disorders, schizophrenia is characterized by deficits on multiple social cognitive domains. In particular, failures of interpersonal coordination (i.e., actions that occur in spatial and temporal concordance with those of other individuals in a social setting) in schizophrenia are closely linked to significant prognostic indicators, such as symptom remission, quality of life, and employment. Despite the increasing interest in the psychological and neural mechanisms of interpersonal coordination in schizophrenia, important gaps in our understanding remain. Notably, the study of the mechanisms underpinning interpersonal coordination is currently undergoing a methodological shift, moving its focus from single-person tasks to second- and multi-person paradigms, and from model-free to model-based analyses. However, applications of these advanced approaches in schizophrenia has been slow. Here, we provide a concise update on the uses of multi-person paradigms to study interpersonal coordination and mathematical models to dissect its computational mechanisms, at both behavioral and neural levels. We then review prior studies on large-scale neuroimaging studies that explore brain correlates of general social functions and further pointed to the implementation of dissecting interpersonal coordination deficits in schizophrenia. Finally, we highlight key challenges as well as exciting opportunities for integrating research in computational psychiatry with second- and multi-person approaches in investigating interpersonal coordination deficits in schizophrenia.

Cognitive markers for efficacy of neurofeedback for attention-deficit hyperactivity disorder – personalized medicine using computational psychiatry in a randomized clinical trial

ABSTRACT Background Exploring whether cognitive components (identified by baseline cognitive testing and computational modeling) moderate clinical outcome of neurofeedback (NF) for attention-deficit hyperactivity disorder (ADHD). Method 142 children (aged 7–10) with ADHD were randomly assigned to either NF (n = 84) or control treatment (n = 58) in a double-blind clinical trial (NCT02251743). The NF group received live, self-controlled downtraining of electroencephalographic theta/beta ratio power. The control group received identical-appearing reinforcement from prerecorded electroencephalograms from other children. 133 (78 NF, 55 control) children had cognitive processing measured at baseline with the Integrated Visual and Auditory Continuous Performance Test (IVA2-CPT) and were included in this analysis. A diffusion decision model applied to the IVA2-CPT data quantified two latent cognitive components deficient in ADHD: drift rate and drift bias, indexing efficiency and context sensitivity of cognitive processes involving information integration. We explored whether these cognitive components moderated the improvement in parent- and teacher-rated inattention symptoms from baseline to treatment end (primary clinical outcome). Results Baseline cognitive components reflecting information integration (drift rate, drift bias) moderated the improvement in inattention due to NF vs. control treatment (p = 0.006). Specifically, those with either the most or least severe deficits in these components showed more improvement in parent- and teacher-rated inattention when assigned to NF (Cohen’s d = 0.59) than when assigned to control (Cohen’s d = −0.21). Conclusions Pre-treatment cognitive testing with computational modeling identified children who benefitted more from neurofeedback than control treatment for ADHD.

Dynamical systems in computational psychiatry: A toy-model to apprehend the dynamics of psychiatric symptoms.

These last years, scientific research focuses on the dynamical aspects of psychiatric disorders and their clinical significance. In this article, we proposed a theoretical framework formalized as a generic mathematical model capturing the heterogeneous individual evolutions of psychiatric symptoms. The first goal of this computational model based on differential equations is to illustrate the nonlinear dynamics of psychiatric symptoms. It offers an original approach to nonlinear dynamics to clinical psychiatrists. In this study, we propose a 3+1 dimensions model (x, y, z + f) reproducing the clinical observations encountered in clinical psychiatry with: a variable modeling environmental noise (z) on the patient's internal factors (y) with its temporal specificities (f) and symptomatology (x). This toy-model is able to integrate empirical or simulated data from the influence of perceived environmental over time, their potential importance on the internal and subjective patient-specific elements, and their interaction with the apparent intensity of symptoms. Constrained by clinical observation of case formulations, the dynamics of psychiatric symptoms is studied through four main psychiatric conditions were modeled: i) a healthy situation, ii) a kind of psychiatric disorder evolving following an outbreak (i.e., schizophrenia spectrum), iii) a kind of psychiatric disorder evolving by kindling and bursts (e.g., bipolar and related disorders); iv) and a kind of psychiatric disorder evolving due to its high susceptibility to the environment (e.g., spersistent complex bereavement disorder). Moreover, we simulate the action of treatments on different psychiatric conditions. We show that the challenges of dynamical systems allow to understand the interactions of psychiatric symptoms with environmental, descriptive, subjective or biological variables. Although this non-linear dynamical model has limitations (e.g., explanatory scope or discriminant validity), simulations provide at least five main interests for clinical psychiatry, such as a visualization of the potential different evolution of psychiatric disorders, formulation of clinical cases, information about attracting states and bifurcations, or the possibility of a nosological refinement of psychiatric models (e.g., staging and symptom network models).

Modelling mood updating: a proof of principle study.

Recent developments in computational psychiatry have led to the hypothesis that mood represents an expectation (prior belief) on the likely interoceptive consequences of action (i.e. emotion). This stems from ideas about how the brain navigates its external world by minimising an upper bound on surprisal (free energy) of sensory information and echoes developments in other perceptual domains. In this paper we aim to present a simple partial observable Markov decision process that models mood updating in response to stressful or non-stressful environmental fluctuations while seeking to minimise surprisal in relation to prior beliefs about the likely interoceptive signals experienced with specific actions (attenuating or amplifying stress and pleasure signals). We examine how, by altering these prior beliefs we can model mood updating in depression, mania and anxiety. We discuss how these models provide a computational account of mood and its related psychopathology and relate it to previous research in reward processing. Models such as this can provide hypotheses for experimental work and also open up the potential modelling of predicted disease trajectories in individual patients.

Computational psychiatry and the lived experience of mental illness

Computational psychiatry and the lived experience of mental illness

The effect of body image dissatisfaction on goal-directed decision making in a population marked by negative appearance beliefs and disordered eating.

Eating disorders are associated with one of the highest mortality rates among all mental disorders, yet there is very little research about them within the newly emerging and promising field of computational psychiatry. As such, we focus on investigating a previously unexplored, yet core aspect of eating disorders-body image dissatisfaction. We continue a freshly opened debate about model-based learning and its trade-off against model-free learning-a proxy for goal-directed and habitual behaviour. We perform a behavioural study that utilises a two-step decision-making task and a reinforcement learning model to understand the effect of body image dissatisfaction on model-based learning in a population characterised by high scores of disordered eating and negative appearance beliefs, as recruited using Prolific. We find a significantly reduced model-based contribution in the body image dissatisfaction task condition in the population of interest as compared to a healthy control. This finding suggests general deficits in deliberate control in this population, leading to habitual, compulsive-like behaviours (body checking) dominating the experience. Importantly, the results may inform treatment approaches, which could focus on enhancing the reliance on goal-directed decision making to help cope with unwanted behaviours.

Active inference, morphogenesis, and computational psychiatry.

Active inference is a leading theory in neuroscience that provides a simple and neuro-biologically plausible account of how action and perception are coupled in producing (Bayes) optimal behavior; and has been recently used to explain a variety of psychopathological conditions. In parallel, morphogenesis has been described as the behavior of a (non-neural) cellular collective intelligence solving problems in anatomical morphospace. In this article, we establish a link between the domains of cell biology and neuroscience, by analyzing disorders of morphogenesis as disorders of (active) inference. The aim of this article is three-fold. We want to: (i) reveal a connection between disorders of morphogenesis and disorders of active inference as apparent in psychopathological conditions; (ii) show how disorders of morphogenesis can be simulated using active inference; (iii) suggest that active inference can shed light on developmental defects or aberrant morphogenetic processes, seen as disorders of information processing, and perhaps suggesting novel intervention and repair strategies. We present four simulations illustrating application of these ideas to cellular behavior during morphogenesis. Three of the simulations show that the same forms of aberrant active inference (e.g., deficits of sensory attenuation and low sensory precision) that have been used to explain psychopathological conditions (e.g., schizophrenia and autism) also produce familiar disorders of development and morphogenesis when implemented at the level of the collective behavior of a group of cells. The fourth simulation involves two cells with too high precision, in which we show that the reduction of concentration signaling and sensitivity to the signals of other cells treats the development defect. Finally, we present the results of an experimental test of one of the model's predictions in early Xenopus laevis embryos: thioridazine (a dopamine antagonist that may reduce sensory precision in biological systems) induced developmental (anatomical) defects as predicted. The use of conceptual and empirical tools from neuroscience to understand the morphogenetic behavior of pre-neural agents offers the possibility of new approaches in regenerative medicine and evolutionary developmental biology.

Revealing human sensitivity to a latent temporal structure of changes

Precisely timed behavior and accurate time perception plays a critical role in our everyday lives, as our wellbeing and even survival can depend on well-timed decisions. Although the temporal structure of the world around us is essential for human decision making, we know surprisingly little about how representation of temporal structure of our everyday environment impacts decision making. How does the representation of temporal structure affect our ability to generate well-timed decisions? Here we address this question by using a well-established dynamic probabilistic learning task. Using computational modeling, we found that human subjects' beliefs about temporal structure are reflected in their choices to either exploit their current knowledge or to explore novel options. The model-based analysis illustrates a large within-group and within-subject heterogeneity. To explain these results, we propose a normative model for how temporal structure is used in decision making, based on the semi-Markov formalism in the active inference framework. We discuss potential key applications of the presented approach to the fields of cognitive phenotyping and computational psychiatry.

Tracking and changing beliefs during social interaction: Where computational psychiatry meets cognitive behavioral therapy.

Tracking and changing beliefs during social interaction: Where computational psychiatry meets cognitive behavioral therapy.

What is Computational Psychiatry Good For?

It is rare in the field of biological psychiatry for hypotheses to be definitively refuted. Rather, topics of investigation drift into and out of fashion, often driven by the initial excitement of technological innovation, followed by the necessary corrective of nuanced or underwhelming clinical results. A well-known example of this is the association between depression and abnormal function of the hypothalamic-pituitary-adrenal axis, as measured using the dexamethasone suppression test (DSST) ( 1 Carroll B.J. Martin F.I. Davies B. Resistance to suppression by dexamethasone of plasma 11-O.H.C.S. levels in severe depressive illness. Br Med J. 1968; 3: 285-287 Crossref PubMed Scopus (219) Google Scholar ). This observation led to a great deal of work investigating whether the association might help us identify useful subtypes of depression ( 2 Schatzberg A.F. Rothschild A.J. Stahl J.B. Bond T.C. Rosenbaum A.H. Lofgren S.B. et al. The dexamethasone suppression test: Identification of subtypes of depression. Am J Psychiatry. 1983; 140: 88-91 Crossref PubMed Scopus (124) Google Scholar ) or help us predict treatment response ( 3 Rush A.J. Weissenburger J. Vasavada N. Orsulak P.J. Fairchild C.J. Dexamethasone suppression test status does not predict differential response to nortriptyline versus amitriptyline. J Clin Psychopharmacol. 1988; 8: 421-425 Crossref PubMed Scopus (1) Google Scholar ). As it turned out, the specificity and predictive value of the DSST was not thought to be of a level that would be useful clinically and the topic has gradually moved out of the spotlight. We are left in the familiar position of knowing that nonsuppression of the DSST is associated with depression, but not being sure how we can use this knowledge to help patients.

The effect of positive autobiographical memory retrieval on decision-making under risk: A computational model-based analysis.

Psychiatric disorders such as depressive and anxiety disorders are associated with altered decision-making under risk. Recent advances in neuroeconomics and computational psychiatry have further discomposed risk-based decision-making into distinct cognitive computational constructs and showed that there may be disorder-specific alterations in these constructs. As a result, it has been suggested these cognitive computational constructs may serve as useful behavioral biomarkers for these disorders. However, to date, little is known about what psychological or behavioral interventions can help to reverse and manage the altered cognitive computational constructs underlying risk-based decision-making. In the present study, we set out to investigate whether recalling positive autobiographical memories may affect risk-based decision-making in healthy volunteers using a description-based task. Specifically, based on theories of behavioral economics, we dissected risk preference into two cognitive computational constructs, utility sensitivity and probability weighting. We found that compared to recalling neutral memories, retrieving positive autobiographical memories increased utility sensitivity (Cohen's d = 0.447), indicating reduced risk aversion. Meanwhile, we also tested the influence of memory retrieval on probability weighting, the effect, however, was unreliable and requires further in-depth investigation. Of clinical relevance, the change in risk aversion after recalling positive memories was in the opposite direction compared to those reported in psychiatric disorders. These results argue for the potential therapeutic effect of positive autobiographical memory retrieval for the amendment of altered risk-based decision-making in psychiatric disorders.

Machine learning approaches for diagnosing depression using EEG: A review.

Depression has become one of the most crucial public health issues, threatening the quality of life of over 300 million people throughout the world. Nevertheless, the clinical diagnosis of depression is now still hampered by behavioral diagnostic methods. Due to the lack of objective laboratory diagnostic criteria, accurate identification and diagnosis of depression remained elusive. With the rise of computational psychiatry, a growing number of studies have combined resting-state electroencephalography with machine learning (ML) to alleviate diagnosis of depression in recent years. Despite the exciting results, these were worrisome of these studies. As a result, ML prediction models should be continuously improved to better screen and diagnose depression. Finally, this technique would be used for the diagnosis of other psychiatric disorders in the future.