Methodological Research On Resting-state Functional Magnetic Resonance Imaging And Its Application In Depression

The emergence of magnetic resonance imaging technology has greatly promoted the development of brain science.Abnormal brain activities may lead to a variety of mental disorders,such as depression.At present,depression has become the world's leading mental illness that brings a heavy economic burden to patients and families,and society.However,the pathological basis and the brain mechanism of its treatment are still unclear.Resting state functional magnetic resonance imaging(fMRI)directly depicts the intrinsically functional organization of the brain by measuring the spontaneous fluctuation of the brain at rest.This technique has been widely used in neuropsychiatric researches.Based on the proposed method of homogeneity of resting state functional connectivity pattern,this thesis mainly investigated the changes of the whole brain functional connectivity pattern of depression and its treatment to explain the brain mechanism of depression and antidepressant effects.First,a large number of studies have revealed that the functions of the brain regions are determined by their external connection patterns.In order to quantitatively study the similarity of the whole brain functional connectivity pattern,we introduced a voxel level method to characterize the consistency of whole-brain functional connectivity patterns-Functional connectivity homogeneity(FcHo).This method uses Kendall's coefficient to measure the similarity of whole-brain functional connectivity patterns of a given voxel with its nearest neighborhood voxels.The robustness and effectiveness of FcHo was validated with different data sets,different neighborhood sizes,intra-subject variability with repeated scanning of each subject,comparison with other similar methods,and application of this method to study the inter-group differences of FcHo between professional Chinese chess players and novices.These results demonstrated that FcHo is a reliable method to measure the similarity of whole-brain functional connectivity patterns,and it may promote future brain cognition and clinical studies.Second,based on our proposed FcHo method,we studied the changed whole-brain functional connectivity patterns in depression.Twenty-seven medication-free major depressive disorder(MDD)patients and thirty-four healthy controls with matching gender,age and education level were collected.FcHo method was used to study the abnormal whole-brain functional connectivity pattern in MDD patients.We found that the FcHo values in the right ventral anterior insula and medial prefrontal lobe of patients of MDD patients were significantly lower than that of the healthy control group and had significant negative correlations with the depression score of the patients.Subsequent functional connectivity analysis found that the functional connectivity between the medial prefrontal cortex and the left angular gyrus significantly reduced and negatively correlated with the patient's depression score.Combined with the meta-analysis,dysfunctions in these core areas of default mode network may lead to abnormalities in mood,social cognition,and top-down regulation,inducing the occurrence of MDD.Third,we applied the FcHo method to study the brain mechanism of electroconvulsive therapy for depression.Due to the quick remission and less adverse reactions,more and more hospitals are adopting electroconvulsive therapy to treat depression,especially for refractory depression with poor medication effect and some patients needing to alleviate their conditions fastly.However,the mechanism of electroconvulsive therapy for depression remains unclear.We used the proposed FcHo method to further study the FcHo changes of MDD patients before and after electroconvulsive therapy.The results showed that the FcHo values in left angular gyrus and dorsal medial prefrontal lobe increased significantly after electroconvulsive therapy.Subsequent functional connectivity analysis found that these two brain regions were mainly connected with default mode network,executive control network and salience network.Moreover the FcHo values of dorsal medial prefrontal cortex and the changed functional connectivity between left angular gyrus and bilateral posterior cerebellar lobe were significantly positively correlated with the changed depression scores in patients.In addition,we found that the changed functional connectivities between the dorsal medial prefrontal lobe and the left parietal sulcus,as well as the left superior and middle frontal gyrus were significantly negatively correlated with changed delayed memory in patients during treatment,which may explain the brain mechanism of the side effects of memory impairment led by electroconvulsive therapy.Finally,the previous studies on depression and electroconvulsive therapy mainly found abnormalities in the default network and the central executive control network,but the role of the insula,as a switch hub between the two networks,in electroconvulsive therapy is a mystery.Particularly,as a heterogeneous brain structure,uncovering the specific subregion of the insula regulating the two networks in depression plays an important role in guiding the future stimulation therapy.In this study,we defined different functional subregions of the insula using the Brainnetome atlas and studied the changes in functional connectivity patterns of each subregion using resting state functional connectivity analysis and effective connectivity analysis.Functional connectivities between the right ventral anterior insula and bilateral dorsolateral prefrontal cortex,left angular gyrus,right angular gyrus,and bilateral caudate nucleus were found to be significantly increased in MDD patients after electroconvulsive therapy.Granger causality analysis showed that the effective connectivity from dorsolateral prefrontal cortex to right angular gyrus was significantly increased after electroconvulsive therapy and was significantly positively correlated with changed depression scores in patients.These findings suggested that electroconvulsive therapy was able to reshape the functional pattern of the ventral salience network to alleviate depressive symptoms.In addition,a trend between the changed functional connectivity of right ventral anterior insula and impaired memory capacity indicated that the heterogeneity of insula function and its key role in brain network information communication.In conclusion,we proposed a whole brain functional connectivity pattern homogeneity method at the voxel level,which provides a new angle of view for investigating the whole brain functional connectivity pattern similarity.Using the proposed method to study depression and electroconvulsive therapy provided an important reference to understand the neuropathological basis and the brain mechanisms of electroconvulsive therapy in depression.Our findings will guide the future early diagnosis and treatment for major depression.