Functional connectivity and glutamate levels of the medial prefrontal cortex in schizotypy are related to sensory amplification in a probabilistic reasoning task.

ABSTRACT

The circular inference (CI) computational model assumes a corruption of sensory data by prior information and vice versa, leading at the extremes to 'see what we expect' (through prior amplification) and/or to 'expect what we see' (through sensory amplification). Although a CI mechanism has been reported in a schizophrenia population, it has not been investigated in individuals experiencing psychosis-like experiences, such as people with high schizotypy traits. Furthermore, the neurobiological basis of CI, such as the link between hierarchical amplifications, excitatory neurotransmission, and resting state functional connectivity (RSFC), remains untested. The participants included in the present study consisted of a subsample of those recruited in a study previously published by our group, Kozhuharova et al. (2021b). We included 36 participants with High (n=18) and Low (n=18) levels of schizotypy who completed a probabilistic reasoning task (the Fisher task) for which individual confidence levels were obtained and fitted to the CI model. Participants also underwent a 1H-Magnetic Resonance Spectroscopy (MRS) scan to measure medial prefrontal cortex (mPFC) glutamate metabolite levels, and a functional Magnetic Resonance Imaging (fMRI) scan to measure RSFC of the medial prefrontal cortex (mPFC). People with high levels of schizotypy exhibited changes in CI parameters, altered cortical excitatory neurotransmission and RSFC that were all associated with sensory amplification. Our findings capture a multimodal signature of CI that is observable in people early in the psychosis spectrum.