Abstract

Hierarchical perceptual-inference models of psychosis may provide a holistic framework for understanding psychosis in schizophrenia including heterogeneity in clinical presentations. Particularly, hypothesized alterations at distinct levels of the perceptual-inference hierarchy may explain why hallucinations and delusions tend to cluster together yet sometimes manifest in isolation. To test this, we used a recently developed resting-state fMRI measure of intrinsic neural timescale (INT), which reflects the time window of neural integration and captures hierarchical brain gradients. In analyses examining extended sensory hierarchies that we first validated, we found distinct hierarchical INT alterations for hallucinations versus delusions in the auditory and somatosensory systems, thus providing support for hierarchical perceptual-inference models of psychosis. Simulations using a large-scale biophysical model suggested local elevations of excitation-inhibition ratio at different hierarchical levels as a potential mechanism. More generally, our work highlights the robustness and utility of INT for studying hierarchical processes relevant to basic and clinical neuroscience.

Highlights

  • Hallucinations and delusions are burdensome symptoms that typically manifest together as the psychotic syndrome of schizophrenia

  • A newly developed method based on resting-state functional magnetic resonance imaging (fMRI) that was validated against electroencephalography (EEG) captures a hierarchy of intrinsic neural timescales (INT), as well as alterations in psychopathology (Watanabe et al, 2019)

  • After further showing excellent reliability of the INT measure, in exploratory analyses, we showed for the first time that patients with schizophrenia have globally reduced INT

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Summary

Introduction

Hallucinations and delusions are burdensome symptoms that typically manifest together as the psychotic syndrome of schizophrenia. Perceptual-inference models of psychosis suggest that these symptoms result from alterations in the updating of internal models of the environment that are used to make inferences about external sensory events and their causes (Adams et al, 2013; Horga and Abi-Dargham, 2019; Sterzer et al, 2018) These models are receiving increasing empirical support (Adams et al, 2018; Baker et al, 2019; Cassidy et al, 2018; Davies et al., 2017; Powers et al, 2017; Teufel et al, 2015), yet current theories do not provide a satisfactory explanation for how hallucinations and delusions tend to co-occur but sometimes manifest in isolation. In addition to these symptom-specific pathways, alterations at any level may naturally propagate throughout the interdependent levels of the hierarchy (Chaudhuri et al, 2015), potentially

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