Enhanced temporal variability of amygdala-frontal functional connectivity in patients with schizophrenia

Abstract

Background: The “dysconnectivity hypothesis” was proposed 20 years ago. It characterized schizophrenia as a disorder with dysfunctional connectivity across a large range of distributed brain areas. Resting-state functional magnetic resonance imaging (rsfMRI) data have supported this theory. Previous studies revealed that the amygdala might be responsible for the emotion regulation-related symptoms of schizophrenia. However, conventional methods oversimplified brain activities by assuming that it remained static throughout the entire scan duration, which may explain why inconsistent results have been reported for the same brain region. Methods: An emerging technique is sliding time window analysis, which is used to describe functional connectivity based on the temporal variability of regions of interest (e.g., amygdala) in patients with schizophrenia. Conventional analysis of the static functional connectivity between the amygdala and whole brain was also conducted. Results: Static functional connectivity between the amygdala and orbitofrontal region was impaired in patients with schizophrenia. The variability of connectivity between the amygdala and medial prefrontal cortex was enhanced (i.e., greater dynamics) in patients with schizophrenia. A negative relationship was found between the variability of connectivity and information processing efficiency. A positive correlation was found between the variability of connectivity and symptom severity. Conclusion: The findings suggest that schizophrenia was related to abnormal patterns of fluctuating communication among brain areas that are involved in emotion regulations. Unveiling the temporal properties of functional connectivity could disentangle the inconsistent results of previous functional connectivity studies. Keywords: Dynamic functional connectivity, Temporal variability, Amygdala, Sliding-window correlation analysis, Schizophrenia