Disrupted default mode network connectivity and its role in negative symptoms of schizophrenia

Schizophrenia is a complex mental disorder characterised by positive symptoms, negative symptoms, and cognitive deficits, with recent studies suggesting that disruptions in the default mode network (DMN) may underlie many of these symptoms. In this study, we used graph theory analysis of resting-state functional magnetic resonance imaging data to investigate differences in the topological organisation and functional connectivity of the DMN in patients with schizophrenia, using two independent datasets of patients and healthy controls. The findings revealed significant group differences in the DMN of patients with schizophrenia, particularly within the core-medial temporal lobe (MTL) subsystem, characterised by lower shortest path length, clustering coefficient, and small-worldness, indicating less efficient network organisation. Weaker functional connectivity in the core-MTL subsystem was correlated with higher avolition-apathy scores, highlighting the role of DMN connectivity patterns in negative symptoms. These results, validated across two independent datasets, emphasise the robust and generalisable association between schizophrenia and DMN network features, less efficient topological properties, and weaker functional connectivity. This underscores the importance of targeting DMN connectivity to alleviate negative symptoms, improve clinical outcomes, and potentially serve as a biomarker for monitoring symptom severity and guiding treatment.