A Study On Functional And Structural Networks Based On Neuroimaging And Its Application In Major Depressive Disorder

Major depressive disorder(MDD)is a common psychiatric disease which was involved in many neural systems and widely distributed brain regions.Many studies about functional magnetic resonance imaging(fMRI)and diffusion tensor imaging(DTI)have suggested that structural and functional abnormalities were observed in MDD.Abnormal local network played a central role in the physiopathology of major depressive disorder.Therefore,investigating the structure and interaction of the abnormal local network associated with MDD is import to the understanding of the structural and functional organization of the brain and its abnormality in the psychiatric disorders.The abnormal functional connectivity within default mode network(DMN),central executive network(CEN)and salience network(SN)were observed in the MDD.Converging findings from previous neuroimaging studies have suggested that antidepressant therapy played an important role in relieving abnormal brain activity in patients with MDD.However,it remains unclear whether such functional abnormalities of DMN,CEN and SN are normalized after a longer period of antidepressant treatment.Therefore,investigating the effect of antidepressant treatment on DMN,CEN and SN in patients with major depressive disorder is a hot issue.Disturbances in emotion regulation are the hallmarks of MDD.Frontal-cingulate network the central emotion regulation neural systems associated with MDD.The amygdala and orbital frontal cortex(OFC)are two critical regions of Frontal-cingulate network.Many studies have revealed that prominent abnormalities structural and functional connectivity between the amygdala and OFC were found in MDD.Another critical question that remains unclear is the exact neural mechanism by which abnormal communications between the amygdala and OFC are modulated in MDD.Meanwhile it is still unknown whether structural connectivity has relationship with effective connectivity between these two nodes.Therefore,investigating amygdala-OFC connectivity in MDD is also a hot issue.However,this method ignores interactions among different abnormal local networks and is hard to demonstrate the whole brain working patterns of MDD.Currently,graph theory and network-based statistic(NBS)analysis have also been applied to investigate alternations of whole-brain structural networks in a MDD cohort using DTI.However,most related studies only use one property(fractional anisotropy,FA)of nerve fibers to construct whole-brain structural brain network.And it is still unknown whether impaired integrity of the white matter fiber tracts has relationship with abnormal topological properties in MDD.Thus,further studying whole brain structural connectivity in MDD is important for the understanding of the physiopathology of major depressive disorder.In accordance with the previous topic,we investigate the network in patients with MDD from prospective of the effect of antidepressant treatment on resting-state functional network,abnormal emotion regulation in Frontal-limbic network and whole brain structural connectivity in MDD.The main works including the following parts:In the first chapter,we investigate the effect of antidepressant treatment on DMN,CEN and SN.First,we used independent component analysis(ICA)to decompose the resting state images into spatially independent components.Then,Two sample t tests were performed to compare the differences of functional connectivity between the pre-treatment and post-treatment MDD group with the control subjects and obtained brain areas with statistical differences.The result indicated that the functional connectivity of cognitive control network in major depressive patients was normalized after a longer period of antidepressant treatment.In the second chapter,we investigated that abnormal emotion regulation in Frontal-limbic network of MDD.First,this study used the template of AAL to choose the amygdala and orbital frontal cortex(OFC).Then,we investigated the anatomical basis of abnormal emotion regulation by tracking the fiber tracts connecting the amygdala and OFC.Finally,we used dynamic casual modelling to detected effective connectivity between amygdala and OFC.Structural connectivity result indicated that we found disrupted structural connectivity of the UF in the patients with MDD,which connects the OFC and amygdala in patients with MDD.Furthermore,the FA value of these fiber tracts was correlated with the severity of the disorder.Our DCM analysis showed that the inhibition of the OFC on the activity of the amygdala was absent in patients with MDD,suggesting that disrupted structural connectivity seems to be modulated through a top-down mechanism.Following 8 weeks of antidepressant treatment,the patients showed significant clinical improvement and normalization of the abnormal OFC-amygdala structural and effective connectivity in the left hemisphere.Our findings suggest that pathways connecting these two nodes may be core targets of the antidepressant treatment.In the third chapter,we investigated whole brain structural connectivity in MDD.First,whole brain structural connectivity matrices were computed for each participant.Then,we compared with MDD and control groups to examine differences in topological properties using graph theoretic analyses.Finally,we examine differences in three interregional connectivity matrixes including FA,Fnum,length of abnormal topological brains in MDD compared with control group.Results demonstrated that abnormal global and local measures of whole-brain structural networks in patients with MDD.our fiber level analysis showed that three abnormal white matter pathways were associated with MDD including inferior longitudinal fasciculus,arcuate fasciculus and cingulum.Finally,we discovered that the FA value of the anterior part of cingulum was correlated with the severity of the disorder.Aiming to answer the problems on the brain network analysis,we investigated brain network in MDD that from two prospectives including abnormal local networks associated with MDD and whole brain structural network in MDD.Abnormal local networks associated with MDD encompassed with the effect of antidepressant treatment on resting-state functional networks and abnormal emotion regulation in Frontal-limbic network.We provide a framework to investigate the networks associated with MDD which could be used in other research.