Multimodal-based Neuroimaging Methodologies And Clinical Applications In Affective And Movement Disroders

Human brain is to date one of the most complicate and elaborate system.The brain cognitive function is involved in neural synchronization between distributed brain areas.Resting state functional magnetic resonance imaging is a powerful analytic tool to explore brain activity at rest.It can characterize the similarity of functional properties at low frequency between brain regions,which is called resting-state functional connectivity.Diffusion tensor imaging can investigate brain microstructures based on the anisotropy of water molecules within brain tissues.It characterizes the brain neural synaptic connectivity,which is the white matter tract-based structural connectivity.Resting-state functional connectivity,as well as white matter structural connectivity have been widely used for studying neuropsychiatric disorders.However,brain structure and function do not exist independently.In contrast,they are interdependent.Therefore,the current thesis will be built on the methods of functional connectivity and structural connectivity,and explore the abnormal connectivity of affective disorder and movement disorder by using multi-model neuroimaging features.The current work will consist of the following parts.1.By employing diffusion tensor imaging,white matter tractography and graph theory,we investigated the topological properties of structural connectivity network in post-traumatic stress disorder.We found that the small world organization was retained in patients.However,the decreased shortest path length and normalized shortest path length were observed.In addition,the brain areas showing altered nodal centralities included salience network,anterior cingulate cortex,pallidum and hippocampus.The results indicated that the post-traumatic stress disorder is a kind of brain system disorder,and provided evidence for understanding functional disturbance and clinical symptoms in the disease.2.We constructed structural connectivity network of drug-free major depressive disorder by employing white matter tractography and used graph theory to investigate the topological properties of structural network.We further applied network-based statistic(NBS)to determine alteration of sub-networks in depression.There were abnormal whole brain topological properties in depression,such as the lowered shortest path length and higher clustering coefficient.Additionally,NBS revealed that major depressive disorder had altered structural connectivity between orbitofrontal cortex and subcortical structures,fusiform gyrus,inferior temporal gyrus and parts of occipital cortex.This study suggested that orbitofrontal connectivity played crucial role in pathology of depression,and provided structural substrates underlying the functional alteration in this disease.3.By using resting-state functional connectivity method,we explored the thalamo-cortical network in currently depressed major depressive disorders and bipolar disorders,and further investigated whether specific thalamo-cortical connectivity could be markers for differentiation between the two disorders.We observed that both patient groups had decreased functional connectivity between thalamus and orbitofrontal cortex,and increased functional connectivity between thalamus and motor/premotor cortex.The thalamo-inferior parietal lobule connection was altered only in bipolar disorder.While the thalamo-temporal and thalamo-somatosensory connections were altered only in major depressive disorder.Moreover,the functional connectivity between inferior pulvinar and left inferior parietal lobule could be used to distinguish bipolar disorder from major depressive disorder.This study suggested that the neuroimaging differences were still found though the similarity of clinical symptoms between the two disorders,and provided biomarkers for clinical diagnosis.4.By combining white matter structural connectivity and resting-state functional connectivity,we explored thalamo-cortical structural connectivity and functional connectivity in paroxysmal kinesigenic dyskinesia.We observed higher functional connectivity and structural connectivity between ventral lateral/anterior nucleus and motor cortex in patients.The functional connectivity was positively correlated with disease duration,suggesting that paroxysmal kinesigenic dyskinesia is a kind of complicated developmental disease.Moreover,we found decreased functional connectivity between mediodorsal neucleus and prefrontal cortex in PRRT2-mutated patients,indicating that PRRT2 mutation decreases thalamo-prefrontal functional integration.The results clarified crucial roles of thalamo-cortical dysconnectivity in pathologies of the disease.Finally,we also investigated basal ganglia-cortical connectivity and found increased functional connectivity between putamen/pallidum and motor cortex in PRRT2-non-mutated patients,suggesting different pathologies between PRRT2-mutated and PRRT2-non-mutated patients.5.By using resting-state functional connectivity analysis,we explored the heterogeneity in patients with paroxysmal kinesigenic dyskinesia.First,we extracted functional connectivity properties using principal component analysis,and applied a density-based clustering algorithm to classify patients into sub-groups.We found that there were two kinds of patients with paroxysmal kinesigenic dyskinesia,one of which was associated with increase in functional connectivity of cerebellum-thalamus-basal ganglia-motor circuits.The other one was involved in decrease in functional connectivity of cerebellum with superior parietal cortex.Moreover,the topological properties of functional connectivity networks were altered in the former kind of patients,but kept unchanged in the latter kind of patients.This study provided a neuroimaging data-driving analytic method for classifying neuropsychiatric disease.