Personal View

Computational psychiatry: a Rosetta Stone linking the brain to mental illness

Attempts to understand psychosis—the experience of profoundly altered perceptions and beliefs—raise questions about how the brain models the world. Standard predictive coding approaches suggest that it does so by minimising mismatches between incoming sensory evidence and predictions. By adjusting predictions, we converge iteratively on a best guess of the nature of the reality. Recent arguments have shown that a modified version of this framework—hybrid predictive coding—provides a better model of how healthy agents make inferences about external reality. We suggest that this more comprehensive model gives us a richer understanding of psychosis compared with standard predictive coding accounts. In this Personal View, we briefly describe the hybrid predictive coding model and show how it offers a more comprehensive account of the phenomenology of delusions, thereby providing a potentially powerful new framework for computational psychiatric approaches to psychosis. We also make suggestions for future work that could be important in formalising this novel perspective.

Vigorous research has been conducted to accumulate biological and theoretical knowledge about neurodevelopmental disorders, including molecular, neural, computational, and behavioral characteristics; however, these findings remain fragmentary and do not elucidate integrated mechanisms. An obstacle is the heterogeneity of developmental pathways causing clinical phenotypes. Additionally, in symptom formations, the primary causes and consequences of developmental learning processes are often indistinguishable. Herein, we review developmental neurorobotic experiments tackling problems related to the dynamic and complex properties of neurodevelopmental disorders. Specifically, we focus on neurorobotic models under predictive processing lens for the study of developmental disorders. By constructing neurorobotic models with predictive processing mechanisms of learning, perception, and action, we can simulate formations of integrated causal relationships among neurodynamical, computational, and behavioral characteristics in the robot agents while considering developmental learning processes. This framework has the potential to bind neurobiological hypotheses (excitation-inhibition imbalance and functional disconnection), computational accounts (unusual encoding of uncertainty), and clinical symptoms. Developmental neurorobotic approaches may serve as a complementary research framework for integrating fragmented knowledge and overcoming the heterogeneity of neurodevelopmental disorders.

Many aspects of health and disease are modeled using the abstraction of a “pathway”—a set of protein or other subcellular activities with specified functional linkages between them. This metaphor is a paradigmatic case of a deterministic, mechanistic framework that focuses biomedical intervention strategies on altering the members of this network or the up-/down-regulation links between them—rewiring the molecular hardware. However, protein pathways and transcriptional networks exhibit interesting and unexpected capabilities such as trainability (memory) and information processing in a context-sensitive manner. Specifically, they may be amenable to manipulation via their history of stimuli (equivalent to experiences in behavioral science). If true, this would enable a new class of biomedical interventions that target aspects of the dynamic physiological “software” implemented by pathways and gene-regulatory networks. Here, we briefly review clinical and laboratory data that show how high-level cognitive inputs and mechanistic pathway modulation interact to determine outcomes in vivo. Further, we propose an expanded view of pathways from the perspective of basal cognition and argue that a broader understanding of pathways and how they process contextual information across scales will catalyze progress in many areas of physiology and neurobiology. We argue that this fuller understanding of the functionality and tractability of pathways must go beyond a focus on the mechanistic details of protein and drug structure to encompass their physiological history as well as their embedding within higher levels of organization in the organism, with numerous implications for data science addressing health and disease. Exploiting tools and concepts from behavioral and cognitive sciences to explore a proto-cognitive metaphor for the pathways underlying health and disease is more than a philosophical stance on biochemical processes; at stake is a new roadmap for overcoming the limitations of today’s pharmacological strategies and for inferring future therapeutic interventions for a wide range of disease states.

This theoretical article revives a classical bridging construct, canalization, to describe a new model of a general factor of psychopathology. To achieve this, we have distinguished between two types of plasticity, an early one that we call ‘TEMP’ for ‘Temperature or Entropy Mediated Plasticity’, and another, we call ‘canalization’, which is close to Hebbian plasticity. These two forms of plasticity can be most easily distinguished by their relationship to ‘precision’ or inverse variance; TEMP relates to increased model variance or decreased precision, whereas the opposite is true for canalization. TEMP also subsumes increased learning rate, (Ising) temperature and entropy. Dictionary definitions of ‘plasticity’ describe it as the property of being easily shaped or molded; TEMP is the better match for this. Importantly, we propose that ‘pathological’ phenotypes develop via mechanisms of canalization or increased model precision, as a defensive response to adversity and associated distress or dysphoria. Our model states that canalization entrenches in psychopathology, narrowing the phenotypic state-space as the agent develops expertise in their pathology. We suggest that TEMP – combined with gently guiding psychological support – can counter canalization. We address questions of whether and when canalization is adaptive versus maladaptive, furnish our model with references to basic and human neuroscience, and offer concrete experiments and measures to test its main hypotheses and implications.

This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

Maladaptive behavior in drug addiction is widely regarded as a result of neurocognitive dysfunctions. Recently, there has been a growing trend to adopt computational methods to study these dysfunctions in drug-addicted patients, not least because it provides a quantitative framework to infer the psychological mechanisms that may have gone awry in addiction. We therefore sought to evaluate the extent to which these theory-driven computational models have fulfilled this purpose in addiction research. We discuss several learning and decision-making theories proposed to explain symptoms that characterize impaired control and the intense urge to use drugs in addiction, and outline the computational algorithms frequently used to model these processes. Specifically, impaired behavioral control over drugs have been explained by aberrant reinforcement learning algorithms and an imbalance between model-based and model-free control, whereas the strong desire for drugs might be explained by a neurocomputational model of incentive sensitization and behavioral economic theory. We argue that while theory-driven computational models may appear to be useful tools that generate novel mechanistic insights into drug addiction, their use should be informed by psychological theory, experimental data, and clinical observations.

Psychiatric disorders encompass complex aberrations of cognition and affect and are among the most debilitating and poorly understood of any medical condition. Current treatments rely primarily on interventions that target brain function (drugs) or learning processes (psychotherapy). A mechanistic understanding of how these interventions mediate their therapeutic effects remains elusive. From the early 1990s, non-invasive functional neuroimaging, coupled with parallel developments in the cognitive neurosciences, seemed to signal a new era of neurobiologically grounded diagnosis and treatment in psychiatry. Yet, despite three decades of intense neuroimaging research, we still lack a neurobiological account for any psychiatric condition. Likewise, functional neuroimaging plays no role in clinical decision making. Here, we offer a critical commentary on this impasse and suggest how the field might fare better and deliver impactful neurobiological insights.