Modular Functional-Metabolic Coupling Alterations of Frontoparietal Network in Schizophrenia Patients

Background: Brain functional dysconnectivity, as well as altered network organization, have been demonstrated to occur in schizophrenia. Brain networks are increasingly understood to exhibit modular community structures, which provides advantages in robustness and functional adaptivity. The frontoparietal network (FPN) serves as an important functional module, and metabolic and functional alterations in the FPN are associated with the pathophysiology of schizophrenia. However, how intra-modular biochemical disruptions lead to inter-modular dysfunction of the FPN, remains unclear. In this study, we aim to investigate alterations in the modular functional-metabolic coupling of the FPN, in patients with schizophrenia. Methods: We combined resting-state functional magnetic resonance imaging (rs-fMRI) and magnetic resonance spectroscopy (MRS) technology and acquired multimodal neuroimaging data in 20 patients with schizophrenia and 26 healthy controls. For the MRS, the dorsolateral prefrontal cortex (DLPFC) region within the FPN was explored. Metabolites including gamma aminobutyric acid (GABA), N-aspart-acetyl (NAA) and glutamate + glutamine (Glx) were quantified, using LCModel software. A graph theoretical approach was applied for functional modular parcellation. The relationship between inter/intra-modular connectivity and metabolic concentration was examined using the Pearson correlation analysis. Moreover, correlations with schizophrenia symptomatology were investigated by the Spearman correlation analysis. Results: The functional topological network consisted of six modules in both subject groups, namely, the default mode, frontoparietal, central, hippocampus, occipital, and subcortical modules. Inter-modular connectivity between the frontoparietal and central modules, and the frontoparietal and the hippocampus modules was decreased in the patient group compared to the healthy controls, while the connectivity within the frontoparietal modular increased in the patient group. Moreover, a positive correlation between the frontoparietal and central module functional connectivity and the NAA in the DLPFC was found in the healthy control group (r = 0.614, p = 0.001), but not in the patient group. Significant functional dysconnectivity between the frontoparietal and limbic modules was correlated with the clinical symptoms of patients. Conclusions: This study examined the links between functional connectivity and the neuronal metabolic level in the DLPFC of SCZ. Impaired functional connectivity of the frontoparietal areas in SCZ, may be partially explained by a neurochemical-functional connectivity decoupling effect. This disconnection pattern can further provide useful insights in the cognitive and perceptual impairments of schizophrenia in future studies.