Altered default mode and fronto-parietal network subsystems in patients with schizophrenia and their unaffected siblings

• Head motion was compared across groups and added as covariate in statistic analysis.
• We detailed the description of participants in the revised manuscript.
• Intra-connectivity abnormality in FPN subsystems was addressed in discussion.
• Explain about siblings’ disrupted intra-connectivity but not inter-connectivity.
• Some recent work were added into the revised manuscript.

The complex symptoms of schizophrenia have recently been linked to disrupted neural circuits and corresponding malfunction of two higher-order intrinsic brain networks: The default mode network (DMN) and the fronto-parietal network (FPN). These networks are both functionally heterogeneous and consist of multiple subsystems. However, the extent to which these subsystems make differential contributions to disorder symptoms and to what degree such abnormalities occur in unaffected siblings have yet to be clarified. We used resting-state functional MRI (rs-fMRI) to examine group differences in intra- and inter-connectivity of subsystems within the two neural networks, across a sample of patients with schizophrenia (n=24), their unaffected siblings (n=25), and healthy controls (n=22). We used group independent component analysis (gICA) to identify four network subsystems, including anterior and posterior portions of the DMN (aDMN, pDMN) as well as left- and right-lateralized portions of the FPN (lFPN, rFPN). Intra-connectivity is defined as neural coherence within a subsystem whereas inter-connectivity refers to functional connectivity between subsystems. In terms of intra-connectivity, patients and siblings shared dysconnection within the aDMN and two FPN subsystems, while both groups preserved connectivity within the pDMN. In terms of inter-connectivity, all groups exhibited positive connections between FPN and DMN subsystems, with patients having even stronger interaction between rFPN and aDMN than the controls, a feature that may underlie their psychotic symptoms. Our results implicate that DMN subsystems exhibit different liabilities to the disease risk while FPN subsystems demonstrate distinct inter-connectivity alterations. These dissociating manners between network subsystems explicitly suggest their differentiating roles to the disease susceptibility and manifestation.