Large-scale maps of altered cortical dynamics in early-stage psychosis are related to GABAergic and glutamatergic neurotransmission.

Abstract

Psychotic disorders affect GABAergic inhibition and glutamatergic excitation via NMDA receptors across the cerebral cortex. The mechanisms by which these distributed synaptic alterations produce the heterogenous symptoms of psychosis remain poorly understood. Using magnetoencephalographical source imaging, we mapped psychosis-related alterations of various features of intrinsic neural population dynamics across the human cortex. The cortex-wide patterns of these features were highly reproducible and related to the anatomical hierarchy of cortical areas. We found similar changes in these patterns for individuals with a first episode of psychosis and those at clinical high risk for psychosis. Maps of psychosis-induced changes in dynamics resembled the maps of GABA-A receptor densities and of pharmacological GABA-A or NMDA manipulation effects on cortical dynamics in healthy participants. The level of pattern similarity to GABA-A manipulation effects in individual patients correlated with positive symptoms, while the pattern similarity to NMDA effects correlated with negative symptoms. Our results open up a window on the distributed mechanisms of psychotic symptoms.