Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective-connectivity, and Computational Evidence in Schizophrenia
R. Limongi, P. Jeon, M. Mackinley, T. Das, K. Dempster, J. Théberge, R. Bartha, Dickson Wong, L. Palaniyappan
bioRxiv November 2, 2019 preprint DOI: 10.1101/828558 (opens in new tab) via Semantic Scholar
Summary
AI-generated from the abstractPsychosis 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.
Study at a glance
| Characteristics | Observational cohort |
|---|---|
| Sample size | 40 |
| Population | First-episode psychosis (FEP) and healthy control (HC) subjects |
| Keywords | Psychology Biology Medicine |
| Key finding | Glutamate concentration in the dACC correlated negatively with inhibitory influence on excitatory neurons in the dACC of first-episode psychosis subjects, supporting a link between glutamate-mediated cortical disinhibition and aberrant connectivity. |
Abstract
In the dysconnection hypothesis, psychosis is caused by NMDA hypofunction resulting in aberrant network connectivity. Combining a cognitive-control task, functional magnetic resonance spectroscopy, and functional magnetic resonance imaging, we tested this hypothesis in the salience network of 20 first-episode psychosis (FEP) and 20 healthy control (HC) subjects. Across groups, glutamate concentration in the dorsal anterior cingulate cortex (dACC) was associated with higher and lower inhibitory connectivity in the dACC and in the anterior insula (AI) respectively. Crucially, glutamate concentration correlated negatively with the inhibitory influence on the excitatory neuronal population in the dACC of FEP subjects. Furthermore, aberrant computational parameters of the cognitive-control task performance were associated with aberrant inhibitory connections. Finally, the strength of connections from the dACC to the AI correlated negatively with severity of social withdrawal. These findings support a link between glutamate-mediated cortical disinhibition, deficits in effective connectivity, and computational performance in psychosis.