Frontal–striatal–thalamic circuit dysfunction and inferential processing between internal representations and external events across the psychosis spectrum

Background: In psychopathology, schizophrenia has been understood as a disorder characterized by disturbances in subjective consciousness. Subjective consciousness and its relationship to interactions between internal representations and external events have been discussed in phenomenology. Recent computational neuroscience conceptualizes the brain as an inferential system that minimizes discrepancies between internal models and latent states inferred from environmental information. From a neurobiological perspective, the frontal–striatal–thalamic circuit may underlie the inferential processing involved in updating internal models based on sensory information derived from the environment.

Aim: In this review, we aimed to examine the theoretical point of contact between phenomenology and computational neuroscience from the perspective of inferential processing within the frontal–striatal–thalamic circuit. An imbalance within this circuit may disrupt inferential processes that minimize discrepancies between internal models and latent states. Such maladaptive inferential processes may distort subjective experiences, potentially contributing to the symptoms observed in At-Risk Mental States (ARMS) and Attenuated Psychosis Syndrome (APS), which are considered clinically high-risk states for psychosis. Based on these considerations, we propose a model linking psychopathological phenomena and neurobiological alterations through the dysfunction of the frontal–striatal–thalamic circuit and associated disturbances in inferential processing. We assessed whether this model was theoretically consistent with previous findings and our own longitudinal studies on ARMS/APS.

Conclusions: This conceptual model may provide a novel perspective on the information-processing mechanisms, particularly inferential processing, and their alterations across high-risk clinical states for psychosis, including ARMS/APS and broader Clinical High At Risk Mental States (CHARMS) concept.