Reduced neuro-integration from the dorsolateral prefrontal cortex to the whole brain and executive dysfunction in schizophrenia patients and their relatives

Executive dysfunction is one of the core symptoms of schizophrenia. Functional neuro-imaging studies have suggested an association between deficits in activating the dorsolateral prefrontal cortex (DLPFC) and executive dysfunction, but neuro-integration from the DLPFC to the whole brain remains unclear. Studies investigating the neuro-integration from the DLPFC to the whole brain in unaffected but genetically liable family members are scant. In this study, we report DLPFC neuro-integrative deficits correlated with executive dysfunction and family history of schizophrenia using resting-state functional magnetic resonance imaging (fMRI). Using seed regions in DLPFC, we examined resting-state functional connectivity in 25 patients with schizophrenia, 25 unaffected first-degree relatives (UR), and 25 healthy control (HC) persons. Schizophrenia patients and UR have impaired connectivity from DLPFC to its coordinated regions (ANOVA: F = 7.316-10.974, p < 0.001). These coordinated brain regions are distributed in the bilateral caudate, left middle/inferior frontal gyrus, left precentral gyrus, and right cerebellum. The individual functional connectivity strength between the left DLPFC and its coordinated regions was correlated with individual executive function performance among whole persons. (Pearson's r = 0.244-0.366, p = 0.035-0.008) Our findings support that distributed neuro-integrative DLPFC deficits reflect a genetic risk for schizophrenia and that these deficits are present, to a lesser degree, in unaffected first-degree relatives. Our findings also support that neuro-integration might correlate with a patient's executive function performance.