Revisiting Functional Dysconnectivity: a Review of Three Model Frameworks in Schizophrenia

Over the last decade, evidence suggests that a combination of behavioral and neuroimaging findings can help illuminate changes in functional dysconnectivity in schizophrenia. We review the recent connectivity literature considering several vital models, considering connectivity findings, and relationships with clinical symptoms. We reviewed resting state fMRI studies from 2017 to 2023. We summarized the role of two sets of brain networks (cerebello-thalamo-cortical (CTCC) and the triple network set) across three hypothesized models of schizophrenia etiology (neurodevelopmental, vulnerability-stress, and neurotransmitter hypotheses).

The neurotransmitter and neurodevelopmental models best explained CTCC-subcortical dysfunction, which was consistently connected to symptom severity and motor symptoms. Triple network dysconnectivity was linked to deficits in executive functioning, and the salience network (SN)-default mode network dysconnectivity was tied to disordered thought and attentional deficits. This paper links behavioral symptoms of schizophrenia (symptom severity, motor, executive functioning, and attentional deficits) to various hypothesized mechanisms.