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bioRxiv · 10.64898/2026.11.10.765658

The extended default mode network dysconnectivity in schizophrenia

Zarghami, T. S.
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Abstract

The default mode network (DMN) extends beyond cortex into subcortical structures, yet how this extended DMN (eDMN) is causally reorganized in schizophrenia (SZ) remains unclear. Here, resting-state fMRI from 74 healthy controls (HC) and 66 SZ patients was analyzed. Subject-specific eDMNs were identified using spatially-constrained independent component analysis, and effective connectivity among 13 regions was estimated with spectral dynamic causal modeling, with group effects assessed using parametric empirical Bayes. Causal centrality--a dynamics-sensitive and causality-based measure of nodal importance--was computed per region, compared between groups, and correlated with MATRICS cognitive scores in patients. Causal centrality rankings were highly similar across groups ({rho} = 0.87), with both favoring subcortical over cortical regions. Group differences were regionally specific: temporal cortex was more causally central in patients, whereas posterior parietal cortex was more causally central in controls. Most connection-level SZ-HC differences originated from ventrolateral prefrontal cortex, prefrontal cortex, basal forebrain, temporal cortex, and thalamus. In patients, temporal causal centrality correlated negatively with reasoning/problem-solving, and ventrolateral prefrontal causal centrality with processing speed and composite cognition. The eDMN's core causal architecture is preserved in schizophrenia, but temporal influence is enhanced and parietal influence attenuated--alterations that are behaviorally meaningful and consistent with pathological reorganization.

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Zarghami, T. S.. 2026-11-12. The extended default mode network dysconnectivity in schizophrenia. https://doi.org/10.64898/2026.11.10.765658

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