Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis

Abstract

Background and Hypothesis Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited. Study Design Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naïve FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses. Study Results We found that the temporal sequence in which patients’ brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naïve FEP sample scanned before and after treatment. Conclusions We conclude that psychosis is related to a temporal disorganization of the brain’s dynamic functional connectivity, and this is associated with antipsychotic medication use.

Cortical Network Disruption is Minimal in Early Stages of Psychosis

“…While we lack longitudinal data to conclusively demonstrate this hypothesis, we cite three lines of evidence supporting this notion. First, functional connectivity is known to be disrupted in FEP, [104][105][106] and long term interregional signalling patterns modify the strength of the connecting tracts, 107,108 and can affect tract myelination. 109 Thus, aberrant functional signalling, over time, may lead to reorganization of the anatomical network.…”

Resting-state functional MRI in treatment-resistant schizophrenia

“…In addition, multimodal MRI studies which consist of structural, diffusion tensor imaging, fMRI, and MR spectroscopy sequences may provide more accurate measures than one modality alone. An interesting future research direction would be to study differences in the effective and dynamic functional connectivity (Ramirez-Mahaluf et al, 2022 ). In fact, none of the studies reviewed applied these connectivity methods in TRS.…”