From hallucinations to synaesthesia: a circular inference account of unimodal and multimodal erroneous percepts in clinical and drug-induced psychosis

Introduction

Hallucinations are percepts experienced in the absence of corresponding external stimulation and occur across clinical, neurological and drug-induced contexts. Classic serotonergic psychedelics (for example LSD, psilocybin, DMT/ayahuasca) typically produce rich visual and multimodal phenomena including synaesthesia, intensified imagery and greater susceptibility to visual illusions. By contrast, schizophrenia more commonly features unimodal auditory hallucinations (voices) often coupled with reduced sensitivity to illusions. These phenomenological differences coexist with distinct neurochemical accounts—serotonergic agonism for psychedelics and dopaminergic dysregulation (with occasional glutamatergic/GABAergic/serotonergic involvement) for schizophrenia—yet a unified mechanistic explanation spanning molecular, circuit and perceptual levels has been lacking. Leptourgos and colleagues set out to provide a multiscale, unifying account of unimodal and multimodal erroneous percepts using the circular inference (CI) framework. They aim to show, using computational simulations and a proposed laminar microcircuit implementation, how different forms of unchecked recurrent information flow (ascending versus descending loops) can produce distinct phenomenological profiles—crossmodal hallucinations and synaesthesia versus segregated unimodal hallucinations—and how these may map onto different inhibitory mechanisms and neuromodulatory influences in cortex. The study therefore links Bayesian/message-passing models at the meso-scale with laminar inhibitory microcircuits at the micro-scale to account for psychotic experiences across drug-induced and clinical states.