Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective-connectivity, and Computational Evidence in Schizophrenia
Roberto Limongi, P. Jeon, Michael Mackinley, T. Das, K. Dempster, J. Théberge, R. Bartha, Dickson Wong, Lena Palaniyappan
bioRxiv November 2, 2019 preprint DOI: 10.1101/828558 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort |
|---|---|
| Sample size | 40 |
| Population | First-episode psychosis (FEP) and healthy control (HC) subjects |
| Key findings | 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.