Computational Psychiatry Research Articles

Generalizable and replicable brain-based predictions of cognitive functioning across common psychiatric illness.

A primary aim of computational psychiatry is to establish predictive models linking individual differences in brain functioning with symptoms. In particular, cognitive impairments are transdiagnostic, treatment resistant, and associated with poor outcomes. Recent work suggests that thousands of participants may be necessary for the accurate and reliable prediction of cognition, questioning the utility of most patient collection efforts. Here, using a transfer learning framework, we train a model on functional neuroimaging data from the UK Biobank to predict cognitive functioning in three transdiagnostic samples (ns = 101 to 224). We demonstrate prediction performance in all three samples comparable to that reported in larger prediction studies and a boost of up to 116% relative to classical models trained directly in the smaller samples. Critically, the model generalizes across datasets, maintaining performance when trained and tested across independent samples. This work establishes that predictive models derived in large population-level datasets can boost the prediction of cognition across clinical studies.

The Ubiquity of Time in Latent-cause Inference.

Humans have an outstanding ability to generalize from past experiences, which requires parsing continuously experienced events into discrete, coherent units, and relating them to similar past experiences. Time is a key element in this process; however, how temporal information is used in generalization remains unclear. Latent-cause inference provides a Bayesian framework for clustering experiences, by building a world model in which related experiences are generated by a shared cause. Here, we examine how temporal information is used in latent-cause inference, using a novel task in which participants see "microbe" stimuli and explicitly report the latent cause ("strain") they infer for each microbe. We show that humans incorporate time in their inference of latent causes, such that recently inferred latent causes are more likely to be inferred again. In particular, a "persistent" model, in which the latent cause inferred for one observation has a fixed probability of continuing to cause the next observation, explains the data significantly better than two other time-sensitive models, although extensive individual differences exist. We show that our task and this model have good psychometric properties, highlighting their potential use for quantifying individual differences in computational psychiatry or in neuroimaging studies.

Three principles for the utility of simple tasks that assess elemental processes in parsing heterogeneity.

As clinical psychological science and biological psychiatry push to assess, model, and integrate heterogeneity and individual differences, approaches leveraging computational modeling, translational methods, and dimensional approaches to psychopathology are increasingly useful in establishing brain-behavior relationships. The field is ultimately interested in complex human behavior, and disruptions in such behaviors can arise through many different pathways, leading to heterogeneity in etiology for seemingly similar presentations. Parsing this complexity may be enhanced using "simple" tasks-which we define as those assaying elemental processes that are the building blocks to complexity. Using eyeblink conditioning as one illustrative example, we propose that simple tasks assessing elemental processes can be leveraged by and enhance computational psychiatry and dimensional approaches in service of understanding heterogeneity in psychiatry, especially when these tasks meet three principles: (a) an extensively mapped circuit, (b) clear brain-behavior relationships, and (c) relevance to understanding etiological processes and/or treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Of strong swords and fine scalpels: Developing robust clinical principles to cut through heterogeneity.

This is an invited commentary article for the special issue. The main thesis is that an effective strategy for computational psychiatry to handle the (possibly intrinsic) heterogeneity of psychiatric disorders is to focus on developing clinical principles rather than solely precision medicine. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Advancing computational psychiatry through a social lens

Advancing computational psychiatry through a social lens

Resting-State Electroencephalogram Depression Diagnosis Based on Traditional Machine Learning and Deep Learning: A Comparative Analysis.

The global prevalence of Major Depressive Disorder (MDD) is increasing at an alarming rate, underscoring the urgent need for timely and accurate diagnoses to facilitate effective interventions and treatments. Electroencephalography remains a widely used neuroimaging technique in psychiatry, due to its non-invasive nature and cost-effectiveness. With the rise of computational psychiatry, the integration of EEG with artificial intelligence has yielded remarkable results in diagnosing depression. This review offers a comparative analysis of two predominant methodologies in research: traditional machine learning and deep learning methods. Furthermore, this review addresses key challenges in current research and suggests potential solutions. These insights aim to enhance diagnostic accuracy for depression and also foster further development in the area of computational psychiatry.

Computing Addiction: Epistemic Injustice Challenges in the Culture of Computational Psychiatry

Computing Addiction: Epistemic Injustice Challenges in the Culture of Computational Psychiatry

Computational psychiatry and the evolving concept of a mental disorder

As a discipline, psychiatry is in the process of finding the right set of concepts to organize research and guide treatment. Dissatisfaction with the status quo as expressed in standard manuals has animated a number of computational paradigms, each proposing to rectify the received concept of mental disorder. We explore how different computational paradigms: normative modeling, network theory and learning-theoretic approaches like reinforcement learning and active inference, reconceptualize mental disorders. Although each paradigm borrows heavily from machine learning, they differ significantly in their methodology, their preferred level of description, the role they assign to the environment and, especially, the degree to which they aim to assimilate psychiatric disorders to a standard medical disease model. By imagining how these paradigms might evolve, we bring into focus three rather different visions for the future of psychiatric research. Although machine learning plays a crucial role in the articulation of these paradigms, it is clear that we are far from automating the process of conceptual revision. The leading role continues to be played by the theoretical, metaphysical and methodological commitments of the competing paradigms.

Neural Reinforcement Learning Signals Predict Recovery From Impulse Control Disorder Symptoms in Parkinson’s Disease

BackgroundImpulse control disorders (ICDs) in Parkinson’s disease are associated with a heavy burden on patients and caretakers. While recovery can occur, ICDs persist in many patients despite optimal management. The basis for this interindividual variability in recovery is unclear and poses a major challenge to personalized health care. MethodsWe adopted a computational psychiatry approach and leveraged the longitudinal, prospective Personalized Parkinson Project (136 people with Parkinson’s disease, within 5 years of diagnosis) to combine dopaminergic learning theory–informed functional magnetic resonance imaging with machine learning (at baseline) to predict ICD symptom recovery after 2 years of follow-up. We focused on change in Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale scores in the entire sample regardless of an ICD diagnosis. ResultsGreater reinforcement learning signals during gain trials but not loss trials at baseline, including those in the ventral striatum and medial prefrontal cortex, and the behavioral accuracy score measured while on medication were associated with greater recovery from impulse control symptoms 2 years later. These signals accounted for a unique proportion of the relevant variability over and above that explained by other known factors, such as decreases in dopamine agonist use. ConclusionsOur results provide a proof of principle for combining generative model–based inference of latent learning processes with machine learning–based predictive modeling of variability in clinical symptom recovery trajectories. We showed that reinforcement learning modeling parameters predicted recovery from ICD symptoms in Parkinson’s disease.

Reliable, rapid, and remote measurement of metacognitive bias

Metacognitive biases have been repeatedly associated with transdiagnostic psychiatric dimensions of ‘anxious-depression’ and ‘compulsivity and intrusive thought’, cross-sectionally. To progress our understanding of the underlying neurocognitive mechanisms, new methods are required to measure metacognition remotely, within individuals over time. We developed a gamified smartphone task designed to measure visuo-perceptual metacognitive (confidence) bias and investigated its psychometric properties across two studies (N = 3410 unpaid citizen scientists, N = 52 paid participants). We assessed convergent validity, split-half and test–retest reliability, and identified the minimum number of trials required to capture its clinical correlates. Convergent validity of metacognitive bias was moderate (r(50) = 0.64, p < 0.001) and it demonstrated excellent split-half reliability (r(50) = 0.91, p < 0.001). Anxious-depression was associated with decreased confidence (β = − 0.23, SE = 0.02, p < 0.001), while compulsivity and intrusive thought was associated with greater confidence (β = 0.07, SE = 0.02, p < 0.001). The associations between metacognitive biases and transdiagnostic psychiatry dimensions are evident in as few as 40 trials. Metacognitive biases in decision-making are stable within and across sessions, exhibiting very high test–retest reliability for the 100-trial (ICC = 0.86, N = 110) and 40-trial (ICC = 0.86, N = 120) versions of Meta Mind. Hybrid ‘self-report cognition’ tasks may be one way to bridge the recently discussed reliability gap in computational psychiatry.

“Minimal self” locked into a model: exploring the prospect of formalizing intentionality in schizophrenia

ABSTRACT Computational psychiatry is a quickly evolving discipline that aims to understand psychopathology in terms of computational, hence algorithmic processes. While cognitive phenomena, especially beliefs or ways of “reasoning”, can more easily be formalized, meaning re-described in mathematical terms and then entered computational models, there is speculation as to whether phenomenology might be formalizable too. In other words, there are speculations in terms of what aspects of the human experience, rather than specific cognitive processes alone, can enter computational models. Here, we explore the possibility of formalizing and modeling a phenomenological account of schizophrenia, using the concepts of “minimal self” and “intentionality”. To test the applicability of these concepts for formalization and modeling, we first aim to clarify some misunderstandings around the very nature of minimal self and intentionality, namely: whether these concepts entail a “minimal” sense of self, or might be better described in “transparent” sensory-integration and information processing terms. We then try to apply the concepts to a computational logic based on Marr’s levels of description, a fundamental account for understanding the rationale of computational psychiatry. Overall, we are asking via what conditions phenomenology can enter a computational logic.

Model-Based Approaches to Investigating Mismatch Responses in Schizophrenia.

Alterations of mismatch responses (ie, neural activity evoked by unexpected stimuli) are often considered a potential biomarker of schizophrenia. Going beyond establishing the type of observed alterations found in diagnosed patients and related cohorts, computational methods can yield valuable insights into the underlying disruptions of neural mechanisms and cognitive function. Here, we adopt a typology of model-based approaches from computational cognitive neuroscience, providing an overview of the study of mismatch responses and their alterations in schizophrenia from four complementary perspectives: (a) connectivity models, (b) decoding models, (c) neural network models, and (d) cognitive models. Connectivity models aim at inferring the effective connectivity patterns between brain regions that may underlie mismatch responses measured at the sensor level. Decoding models use multivariate spatiotemporal mismatch response patterns to infer the type of sensory violations or to classify participants based on their diagnosis. Neural network models such as deep convolutional neural networks can be used for improved classification performance as well as for a systematic study of various aspects of empirical data. Finally, cognitive models quantify mismatch responses in terms of signaling and updating perceptual predictions over time. In addition to describing the available methodology and reviewing the results of recent computational psychiatry studies, we offer suggestions for future work applying model-based techniques to advance the study of mismatch responses in schizophrenia.

Hallucinating mice, psychotherapy in the brain, and computational psychiatry: the future of psychiatry is now.

Hallucinating mice, psychotherapy in the brain, and computational psychiatry: the future of psychiatry is now.

Does the reliability of computational models truly improve with hierarchical modeling? Some recommendations and considerations for the assessment of model parameter reliability : Reliability of computational model parameters.

Computational modeling of behavior is increasingly being adopted as a standard methodology in psychology, cognitive neuroscience, and computational psychiatry. This approach involves estimating parameters in a computational (or cognitive) model that represents the computational processes of the underlying behavior. In this approach, the reliability of the parameter estimates is an important issue. The use of hierarchical (Bayesian) approaches, which place a prior on each model parameter of the individual participants, is thought to improve the reliability of the parameters. However, the characteristics of reliability in parameter estimates, especially when individual-level priors are assumed, as in hierarchical models, have not yet been fully discussed. Furthermore, the suitability of different reliability measures for assessing parameter reliability is not thoroughly understood. In this study, we conduct a systematic examination of these issues through theoretical analysis and numerical simulations, focusing specifically on reinforcement learning models. We note that the heterogeneity in the estimation precision of individual parameters, particularly with priors, can skew reliability measures toward individuals with higher precision. We further note that there are two factors that reduce reliability, namely estimation error and intersession variation in the true parameters, and we discuss how to evaluate these factors separately. Based on the considerations of this study, we present several recommendations and cautions for assessing the reliability of the model parameters.

Unique Time-Series Patterns of Behavioral and Psychological Factors in Late-Life Depression: A Computational Psychiatry Approach with Hidden Markov Models

Unique Time-Series Patterns of Behavioral and Psychological Factors in Late-Life Depression: A Computational Psychiatry Approach with Hidden Markov Models

Benchmarking Mental Health Status Using Passive Sensor Data: Protocol for a Prospective Observational Study.

Computational psychiatry has the potential to advance the diagnosis, mechanistic understanding, and treatment of mental health conditions. Promising results from clinical samples have led to calls to extend these methods to mental health risk assessment in the general public; however, data typically used with clinical samples are neither available nor scalable for research in the general population. Digital phenotyping addresses this by capitalizing on the multimodal and widely available data created by sensors embedded in personal digital devices (eg, smartphones) and is a promising approach to extending computational psychiatry methods to improve mental health risk assessment in the general population. Building on recommendations from existing computational psychiatry and digital phenotyping work, we aim to create the first computational psychiatry data set that is tailored to studying mental health risk in the general population; includes multimodal, sensor-based behavioral features; and is designed to be widely shared across academia, industry, and government using gold standard methods for privacy, confidentiality, and data integrity. We are using a stratified, random sampling design with 2 crossed factors (difficulties with emotion regulation and perceived life stress) to recruit a sample of 400 community-dwelling adults balanced across high- and low-risk for episodic mental health conditions. Participants first complete self-report questionnaires assessing current and lifetime psychiatric and medical diagnoses and treatment, and current psychosocial functioning. Participants then complete a 7-day in situ data collection phase that includes providing daily audio recordings, passive sensor data collected from smartphones, self-reports of daily mood and significant events, and a verbal description of the significant daily events during a nightly phone call. Participants complete the same baseline questionnaires 6 and 12 months after this phase. Self-report questionnaires will be scored using standard methods. Raw audio and passive sensor data will be processed to create a suite of daily summary features (eg, time spent at home). Data collection began in June 2022 and is expected to conclude by July 2024. To date, 310 participants have consented to the study; 149 have completed the baseline questionnaire and 7-day intensive data collection phase; and 61 and 31 have completed the 6- and 12-month follow-up questionnaires, respectively. Once completed, the proposed data set will be made available to academic researchers, industry, and the government using a stepped approach to maximize data privacy. This data set is designed as a complementary approach to current computational psychiatry and digital phenotyping research, with the goal of advancing mental health risk assessment within the general population. This data set aims to support the field's move away from siloed research laboratories collecting proprietary data and toward interdisciplinary collaborations that incorporate clinical, technical, and quantitative expertise at all stages of the research process. DERR1-10.2196/53857.

Biosignal comparison for autism assessment using machine learning models and virtual reality

Clinical assessment procedures encounter challenges in terms of objectivity because they rely on subjective data. Computational psychiatry proposes overcoming this limitation by introducing biosignal-based assessments able to detect clinical biomarkers, while virtual reality (VR) can offer ecological settings for measurement. Autism spectrum disorder (ASD) is a neurodevelopmental disorder where many biosignals have been tested to improve assessment procedures. However, in ASD research there is a lack of studies systematically comparing biosignals for the automatic classification of ASD when recorded simultaneously in ecological settings, and comparisons among previous studies are challenging due to methodological inconsistencies. In this study, we examined a VR screening tool consisting of four virtual scenes, and we compared machine learning models based on implicit (motor skills and eye movements) and explicit (behavioral responses) biosignals. Machine learning models were developed for each biosignal within the virtual scenes and then combined into a final model per biosignal. A linear support vector classifier with recursive feature elimination was used and tested using nested cross-validation. The final model based on motor skills exhibited the highest robustness in identifying ASD, achieving an AUC of 0.89 (SD = 0.08). The best behavioral model showed an AUC of 0.80, while further research is needed for the eye-movement models due to limitations with the eye-tracking glasses. These findings highlight the potential of motor skills in enhancing objectivity and reliability in the early assessment of ASD compared to other biosignals.

Temporal imprecision of phase coherence in schizophrenia and psychosis-dynamic mechanisms and diagnostic marker.

Schizophrenia (SCZ) is a complex disorder in which various pathophysiological models have been postulated. Brain imaging studies using EEG/MEG and fMRI show altered amplitude and, more recently, decrease in phase coherence in response to external stimuli. What are the dynamic mechanisms of such phase incoherence, and can it serve as a differential-diagnostic marker? Addressing this gap in our knowledge, we uniquely combine a review of previous findings, novel empirical data, and computational-dynamic simulation. The main findings are: (i) the review shows decreased phase coherence in SCZ across a variety of different tasks and frequencies, e.g., task- and frequency-unspecific, which is further supported by our own novel data; (ii) our own data demonstrate diagnostic specificity of decreased phase coherence for SCZ as distinguished from major depressive disorder; (iii) simulation data exhibit increased phase offset in SCZ leading to a precision index, in the millisecond range, of the phase coherence relative to the timing of the external stimulus. Together, we demonstrate the key role of temporal imprecision in phase coherence of SCZ, including its mechanisms (phase offsets, precision index) on the basis of which we propose a phase-based temporal imprecision model of psychosis (PTP). The PTP targets a deeper dynamic layer of a basic disturbance. This converges well with other models of psychosis like the basic self-disturbance and time-space experience changes, as discussed in phenomenological and spatiotemporal psychopathology, as well as with the models of aberrant predictive coding and disconnection as in computational psychiatry. Finally, our results show that temporal imprecision as manifest in decreased phase coherence is a promising candidate biomarker for clinical differential diagnosis of SCZ, and more broadly, psychosis.

Understanding anxiety through uncertainty quantification.

Uncertainty has been a central concept in psychological theories of anxiety. However, this concept has been plagued by divergent connotations and operationalizations. The lack of consensus hinders the current search for cognitive and biological mechanisms of anxiety, jeopardizes theory creation and comparison, and restrains translation of basic research into improved diagnoses and interventions. Drawing upon uncertainty decomposition in Bayesian Decision Theory, we propose a well-defined conceptual structure of uncertainty in cognitive and clinical sciences, with a focus on anxiety. We discuss how this conceptual structure provides clarity and can be naturally applied to existing frameworks of psychopathology research. Furthermore, it allows formal quantification of various types of uncertainty that can benefit both research and clinical practice in the era of computational psychiatry.

Cognitive equilibrium and instability : Lyapunov stability analysis in mental health research

Mental well-being is often seen as a fragile state, akin to a tightrope walk of balance. In our paper, “Cognitive Equilibrium and Instability: Lyapunov Stability Analysis in Mental Health Research,” we explore the nuanced dance between consistency and change in the realm of cognitive function. Drawing on Lyapunov Stability principles from the study of dynamic systems, we offer new perspectives on mental health mechanics. We propose that the mind is in a state of perpetual flux, constantly adjusting to a spectrum of influences to maintain cognitive balance. Our work involves identifying these points of balance and assessing their robustness using Lyapunov Stability Analysis. We examine how various factors, such as stress, environmental changes, and biological variations, can disrupt this balance, possibly leading to states of well-being or illness. Through our models, we illuminate the evolution and path of mental health conditions. Our methodology is a synthesis of theoretical models and real-world data, including neuroimaging, clinical, and psychological evaluations. Case studies in our paper demonstrate the application of our models to conditions like anxiety, depression, and bipolar disorder, revealing the fluid nature of these ailments. This work goes on to discuss the practical implications of our findings in the clinical setting. By identifying pivotal points of potential instability, our model serves as a tool for early identification of mental health concerns, guiding the creation of specific therapeutic interventions. Additionally, our work supports a tailored approach to mental health care, appreciating the individual cognitive patterns unique to each person. Our paper contributes to the burgeoning field of computational psychiatry, blending mathematical analysis with a perspective centered on the human experience. It sets the stage for future interdisciplinary research aimed at decoding the intricacies of the human psyche.