Dataset Information

A multimodal neuroimaging study investigating resting-state connectivity, glutamate and GABA at 7 T in first-episode psychosis.

ABSTRACT:

Background

The major excitatory and inhibitory neurometabolites in the brain, glutamate and γ-aminobutyric acid (GABA), respectively, are related to the functional MRI signal. Disruption of resting-state functional MRI signals has been reported in psychosis spectrum disorders, but few studies have investigated the role of these metabolites in this context.

Methods

We included 19 patients with first-episode psychosis and 21 healthy controls in this combined magnetic resonance spectroscopy (MRS) and resting-state functional connectivity study. All imaging was performed on a Siemens Magnetom 7 T MRI scanner. Both the MRS voxel and the seed for functional connectivity analysis were located in the dorsal anterior cingulate cortex (ACC). We used multiple regressions to test for an interaction between ACC brain connectivity, diagnosis and neurometabolites.

Results

ACC brain connectivity was altered in first-episode psychosis. The relationship between ACC glutamate and ACC functional connectivity differed between patients with first-episode psychosis and healthy controls in the precuneus, retrosplenial cortex, supramarginal gyrus and angular gyrus. As well, the relationship between ACC GABA and ACC functional connectivity differed between groups in the caudate, putamen and supramarginal gyrus.

Limitations

We used a small sample size. As well, although they were not chronically medicated, all participants were medicated during the study.

Conclusion

We demonstrated a link between the major excitatory and inhibitory brain metabolites and resting-state functional connectivity in healthy participants, as well as an alteration in this relationship in patients with first-episode psychosis. Combining data from different imaging modalities may help our mechanistic understanding of the relationship between major neurometabolites and brain network dynamics, and shed light on the pathophysiology of first-episode psychosis.

SUBMITTER: Overbeek G

PROVIDER: S-EPMC8695527 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Disorders with psychotic features, including schizophrenia and some bipolar disorders, are associated with impairments in regulation of goal-directed behavior, termed cognitive control. Cognitive control-related neural alterations have been studied in psychosis. However, studies are typically unimodal, and relationships across modalities of brain function and structure remain unclear. Thus, we performed transdiagnostic multimodal analyses to examine cognitive control-related neural variation in psychosis. METHODS:Structural, resting, and working memory task imaging for 31 control participants, 27 participants with bipolar disorder, and 23 participants with schizophrenia were collected and processed identically to the Human Connectome Project, enabling identification of relationships with prior multimodal work. Two cognitive control-related independent components (ICs) derived from the Human Connectome Project using multiset canonical correlation analysis with joint IC analysis were used to predict performance in psychosis. De novo multiset canonical correlation analysis with joint IC analysis was performed, and the results were correlated with cognitive control. RESULTS:A priori working memory and cortical thickness maps significantly predicted cognitive control in psychosis. De novo multiset canonical correlation analysis with joint IC analysis identified an IC correlated with cognitive control that also discriminated groups. Structural contributions included insular and cingulate regions; task contributions included precentral, posterior parietal, cingulate, and visual regions; and resting-state contributions highlighted canonical network organization. Follow-up analyses suggested that correlations with cognitive control were primarily influenced by participants with schizophrenia. CONCLUSIONS:A priori and de novo imaging replicably identified a set of interrelated patterns across modalities and the healthy-to-psychosis spectrum, suggesting robustness of these features. Relationships between imaging and cognitive control performance suggest that shared symptomatology may be key to identifying transdiagnostic relationships in psychosis.