Study Of Cognitive Impairment In Patients With Major Depressive Disorder Based On Resting-state FMRI And DTI

Major depressive disorder(MDD)is a kind of mental disease with emotional dysregulation and cognitive impairment,which imposes a heavy burden on family and society.Although preliminary progress has been made in the study of pathological mechanism of depression,there is currently no objective biomarker approach for diagnosis and treatment of depression due to the complexity of its pathogenesis.In this case,it is easy to cause misdiagnosis depending on the doctor's own experience or the relevant scales.To promote the change of diagnosis and therapeutic evaluation of depression from qualitative to quantitative,it is necessary to explore the neurophysiological mechanism related to the pathogenesis of MDD.To overcome the limitations of previous studies that often use data from a certain modality,based on the systematic methodology of brain informatics,multimodal data are acquired including resting-state fMRI,diffusion tensor imaging(DTI),and clinical status and behavioral data in this study.Then,a systematic study of abnormal neural pathways leading to depression and its biological markers are performed from functional,structural,and behavioral perspective,which provide new insights for understanding the underlying neural mechanism of emotional dysregulation and cognitive impairment in patients with MDD.And the study filled the gap in the pathology study of MDD.The main innovations,research methods and conclusions of this thesis are as follows:1.In view of the fact that the relationship between arithmetic ability and white matter fiber tracts remains unclear in healthy adults,the relationship between these changes in the integrity of white matter fiber tracts and the ability to addition,subtraction,and number matched in the individuals was examined.The results demonstrate that the capabilities of mental arithmetic are related to the level of fiber tracts coherence or myelination.Specifically,the right superior longitudinal fasciculus(temporal part)of white matter fiber tracts are possible to be used together in addition,subtraction,and number matched operations,while the right cingulum(cingulate gyrus)and the right inferior longitudinal fasciculus may be related to the more use of quantity-based procedural strategies in subtraction operation.These results indicated that the enhancement of white matter fasciculus coherence and myelination,that is,the increase of FA,may be a potential neural mechanism for the improvement of arithmetic ability.The analysis of the mental arithmetic neural mechanism helps to understand the human information processing system in advanced cognitive functions.2.The previous studies of MDD-related functional brain network often only examined the nodal properties in a certain connection density,and the pathological attack attributes were not investigated.The resilience and systematic analysis of nodal properties were proposed to verify the hypothesis that the attacked regions are mostly hub nodes.Therefore,based on resting-state fMRI,we constructed a series of functional brain network with connection density in the range 0–100% in increments of 2%.And these networks were systematically analyzed by graph theory.It was found that the functional brain network of depressed patients relative to HC groups tends to be randomized and has greater resilience under targeted attacks.Further analysis of the nodal properties revealed the abnormal clustering coefficient or nodal efficiency in the limbic system,salience network,and default mode network,most of which associated with clinical status of MDD.The comprehensive performance of the abnormal nodal properties is the decrease of clustering coefficient and the increase of nodal efficiency,that is,the role of these nodes in local or specialized processing is weakened,and their role in the whole brain integrity is enhanced.This may be an endophenotype and provide new insights into the pathologic mechanism of MDD.In addition,the equal connection density between the two groups was constrained in previous studies,which may ignore the intrinsic differences of the functional connectivity(FC).The method was proposed by maximizing intrinsic FC to estimate the changes in functional brain network efficiency in patients with MDD.It was found that the prefrontal-limbicl system was damaged,and there was a decrease in nodal efficiency or local efficiency in these regions in depressed patients.It provides a new perspective for revealing the abnormal interaction of functional brain network in patients with MDD.3.In view of the fact that the relationship between FC and structural connectivity(SC)remains unclear in patients with MDD.To this end,FC was estimated by the correlation coefficient based on resting-state fMRI,and SC was determined by the number of fiber tracts derived from the probabilistic tractography algorithm based on DTI.Compared to the HC group,abnormal FC in the MDD group were found mainly in the frontal-striatal-thalamic circuit,and between this circuit and the cerebellum.More importantly,the SC and FC between the left thalamus and the left pallidum were found to be reduced simultaneously.It supports that the abnormality in the frontal-striatal-thalamic circuit plays an important role in the neuropathological mechanism of MDD.Further,it was also found that cognitive impairment in patients with MDD is related to abnormal FC between the right pallidum and the right middle frontal gyrus.And the abnormal FC between the left thalamus and the left pallidum was negatively correlated with the anxiety level of depressed patients.These results demonstrated that the abnormalities SC or FC among the frontal-striatal-thalamic circuit and the cerebellum may be the neural mechanisms of emotional dysregulation and cognitive impairment in patients with MDD.In addition,through the study of emotion-cognition interaction and the integrity of white matter fiber tracts in patients with MDD,it was found that patients with MDD have the bias of cognitive impairment under the stimulation of three types of pictures.And the accuracy of subtraction of MDD group under the stimulation of neutral pictures was significantly less than that of the HC group.It suggest that the cognitive function of depressed patients is indeed damaged.Then,the decrease of FA values in the splenium of corpus callosum and corticospinal tract,as well as the increase of FA values in anterior thalamic radiation and bilateral cerebral peduncle was found by the voxel-based analysis in patients with MDD compared to the HC group.These results suggest that the integrity of the white matter fiber tracts in the patients with MDD is not only damaged,but may also be accompanied by a compensatory regeneration mechanism.It provides new evidences for a better understanding of the role of white matter abnormalities in the pathology of depression.Through systematic analysis of multimodal data including resting-state fMRI,DTI,clinical status,and cognitive experiments in patients with MDD,the preliminary conclusions related to functional,structural,and behavioral aspects were obtained.These have very important reference value and signification for understanding the pathological features associated with MDD.It will help psychiatrists to establish a standard diagnostic and therapeutic assessment method for MDD,so as to improve the effectiveness of diagnosis and treatment strategies,and reduce the burden of family and society.