Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective-connectivity, and Computational Evidence in Schizophrenia
bioRxiv November 2, 2019 R. Limongi, P. Jeon, M. Mackinley et al. preprint
Psychosis may arise from disrupted brain connectivity caused by insufficient NMDA receptor activity. In a study of 20 people with first-episode psychosis and 20 healthy controls, glutamate levels in the dorsal anterior cingulate cortex (dACC) were linked to altered inhibitory connections within the salience network. Specifically, higher glutamate correlated with weaker inhibitory influence on excitatory neurons in the dACC among those with psychosis. Abnormalities in cognitive-control task performance were tied to these disrupted connections, and the strength of connections from the dACC to the anterior insula was inversely related to social withdrawal severity. The findings suggest that glutamate-driven disinhibition contributes to connectivity deficits and cognitive impairments in psychosis.