Brain network connectivity in individuals with schizophrenia and their siblings

Abstract

Background: Research on brain activity in schizophrenia has shown that changes in the function of any single region cannot explain the range of cognitive and affective impairments in this illness. Rather, neural circuits that support sensory, cognitive, and emotional processes are now being investigated as substrates for cognitive and affective impairments in schizophrenia, a shift in focus consistent with long-standing hypotheses about schizophrenia as a disconnection syndrome. Our goal was to further examine alterations in functional connectivity within and between the default mode network and three cognitive control networks (frontal-parietal, cingulo-opercular, and cerebellar) as a basis for such impairments.

Methods: Resting state functional magnetic resonance imaging was collected from 40 individuals with DSM-IV-TR schizophrenia, 31 siblings of individuals with schizophrenia, 15 healthy control subjects, and 18 siblings of healthy control subjects while they rested quietly with their eyes closed. Connectivity metrics were compared between patients and control subjects for both within- and between-network connections and were used to predict clinical symptoms and cognitive function.

Results: Individuals with schizophrenia showed reduced distal and somewhat enhanced local connectivity between the cognitive control networks compared with control subjects. Additionally, greater connectivity between the frontal-parietal and cerebellar regions was robustly predictive of better cognitive performance across groups and predictive of fewer disorganization symptoms among patients.

Conclusions: These results are consistent with the hypothesis that impairments of executive function and cognitive control result from disruption in the coordination of activity across brain networks and additionally suggest that these might reflect impairments in normal pattern of brain connectivity development.

Figure 1

Figure illustrating the location of regions within each of the four networks. Regions of the Frontal-Parietal network (FP) are marked in green, the Cingulo-Opercular network (CO) in yellow, the Default Mode Network (DMN) in blue and the Cerebellar network (CER) in red.

Figure 2

Graph illustrating within network connectivity in each of the four groups. SCZ = individuals with schizophrenia; SCZ-SIB = siblings of individuals with schizophrenia; CON = healthy controls; CON-SIB = siblings of healthy controls: DMN = Default Mode Network; FP = Frontal Parietal Network; CO = Cingulo-Opercular Network; CER = Cerebellar Network; w = within. Segments marked in blue indicate networks for which group differences did not reach statistical significance.

Figure 3

Graph illustrating between network connectivity in each of the four groups. SCZ = individuals with schizophrenia; SCZ-SIB = siblings of individuals with schizophrenia; CON = healthy controls; CON-SIB = siblings of healthy controls: DMN = Default Mode Network; FP = Frontal Parietal Network; CO = Cingulo-Opercular Network; CER = Cerebellar Network; b= between. Segments marked in red indicate networks for which connectivity measures showed significant diagnostic group differences. For those networks, the shaded boxes delineate the diagnostic groups (pink = individuals with schizophrenia and their siblings; purple = healthy controls and their siblings). Segments marked in blue indicate networks for which group differences did not reach statistical significance.