Altered resting-state functional connectivity in delusional patients with schizophrenia or schizoaffective disorder:...

Delusions are a core symptom of schizophrenia and schizoaffective disorder (SCZ/SZA), yet their neural mechanisms remain incompletely understood. Contemporary models emphasize dysfunctional network-level interactions, particularly between subcortical and cortical regions.

To characterize resting-state functional connectivity (rsFC) alterations specifically associated with prominent delusions in SCZ/SZA, with emphasis on cortico-subcortical and cerebellar networks.

High-resolution ROI-to-ROI rsFC analyses were conducted in 20 SCZ/SZA patients with prominent delusions and 20 matched healthy controls. Functional connectivity was calculated across 164 regions using the Harvard-Oxford atlas. Statistical significance was assessed with threshold-free cluster enhancement (TFCE) and family-wise error (FWE) correction at p < 0.05.

Twenty significant connectivity clusters were identified, encompassing both hyper- and hypoconnectivity. Increased connectivity was observed between basal ganglia structures (putamen, pallidum) and cortical regions of the default mode network (DMN), frontal executive networks, and limbic areas, consistent with aberrant salience attribution and disrupted integration of internal and external signals.

Delusions in SCZ/SZA may stem from widespread dysconnectivity anchored in evolutionarily older subcortical and cerebellar regions, impairing sensorimotor, emotional, and cognitive integration. These findings support a network-based model of delusion formation and may inform potential targets for neuromodulatory intervention.