Effective Connectivity Research On The Resting State Function Magnetic Resonance Imaging Of The First-episode Treatment-naive Depression

Objectives:Many studies confirmed that Major Depressive Disorder (MDD) patients’ Prefrontal-Limbic Network (PLN) has a number of anomalies in brain structure and function. Granger causality analysis (GCA) can be effectively applied to resting-state fMRI research. We use the technology to study variation of effective connectivity in PLN of first-episode treatment-naive patients, relations among abnormal effective connectivity, severity of illness and cognitive function will be discussed.Materials and Methods:23patients with major depressive disorder (MDD)(aged31.1±1.5, all right-handed) participated in this study, the control group used20normal volunteers with matched gender and age, Hamilton Depression Scale (HAMD), Montgomery-Asberg Depression Scale (MADRS) and Hamilton Anxiety Scale (HAMA) were respectively used for assessment of patients’condition, and then Stroop Color Word Test (SCWT) and Trail Making Test (TMT) were used for cognitive function test. After completion of neuropsychological test, resting-state functional magnetic resonance imaging (fMRI) was done. After data preprocessing, REST-GCA software package was used, the results of anterior cingulate cortex (ACC) in the Meta analysis of MDD were used as the coordinates of the seed point for GCA analysis based on coefficient, two-sample t test was used for analysis of the differences of effective connectivity between the two groups. Finally abnormal effective connectivities with significant statistical differences in the MDD were extracted, the value of GCA in the brain region was changed for correlation analysis with results of clinical scale and cognitive function.Results:The cognitive function test for two groups of subjects did not show significant statistical difference. In the analysis results of resting-state fMRI, compared to the normal control group, the regions of MDD patients where the effective connectivity from the whole brain to ACC increased were mainly right insular cortex (fAI) and right putamen, while brain regions where effective connectivity decreased were mainly bilateral dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC) and left orbitofrontal cortex (OFC). The effective connectivity from ACC to the whole brain did not show significant statistical difference. In the a posteriori correlation analysis of clinical cognition, the effective connectivities from left and right DLPFC to ACC of the MDD patients were negatively correlated to the completion time of TMT-A, the value of GCA of the effective connectivity from MPFC to ACC was also negatively correlated to the completion time of TMT-A; the effective connectivity of right DLPFC was also weakly negatively correlated to the completion time of TMT-B. Conclusion:The change of effective connectivity of bilateral dorsolateral frontal cortex proved that top-down cognitive control function reduction existed in MDD and revealed potential executive function and attention function impairment of MDD patients. The abnormality of effective connectivity from rAI to ACC showed that the SN switching in the resting state had problems, plus the change of effective connectivity from the striatum to ACC, it was further verified that the loop of limbic cortex-striatum-globus-pallidus-thalamic lost balance these specific abnormal connections further supplemented the dynamic active process of PLN of MDD patients and reflected the abnormal change of baseline of neural activities under non-task state. These findings could help us distinguish and understand the pathogenesis of MDD.