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 and only partially understood, the individual symptomatology is heterogenous, and there is a lack of biomarkers for the early detection, diagnosis, and individualized treatment. The underlying synaptic and microcircuitry alterations are widely distributed across the cerebral cortex. Here, we developed a magnetoencephalography approach to map the resulting cortex-wide alterations of local cortical population dynamics. We identified large-scale patterns of changes in cortical 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 first-episode psychosis patients related to individual symptomatology. Our approach and results open a window on the distributed pathophysiology of psychosis.