Large-scale Dynamical Fingerprints of Distributed Synaptic Alterations in Early-Stage Psychosis

Psychotic disorders, such as schizophrenia, present a major challenge for research and clinical practice: its pathogenesis is complex, the individual symptomatology is heterogenous, and there is a lack of biomarkers for the early detection, diagnosis, and individualized treatment. Mounting evidence indicates that the synaptic and microcircuitry alterations underlying psychosis are widely distributed in the brain. Here, we developed a magnetoencephalography approach to map the resulting alterations of local cortical population dynamics across the human cerebral cortex. We identified large-scale patterns of changes in neural dynamics that were remarkably similar between first-episode psychosis patients and individuals at clinical high risk for psychosis. These spatial patterns also resembled those induced by pharmacological manipulations of excitatory NMDA glutamate receptors and inhibitory GABA-A receptors in healthy participants. Differences in those spatial patterns of cortical dynamics between psychosis patients related to individual symptomatology. Our study opens a new window on the distributed pathophysiology of psychosis. TeaserCortex-wide changes in neural mass dynamics due to psychosis resemble changes due to GABA-A or NMDA receptor manipulation and relate to clinical symptoms.