Research On The Connectome Gradient And Structural Foundation In The Cerebellum With The Generalized Epilepsy

Epilepsy is a chronic neurological disease caused by the synchronous discharge of complex nerve cells in the brain.General tonic-clonic seizures（GTCS）is one of the common subtype in the idiopathic generalized epilepsy（IGE）,which is characterized by sustained tonic contraction and convulsion of muscles all over the body,abnormal activity of the neurons,accompanied by repeated and transient behavioral cognitive dysfunction,even loss of consciousness,and no obvious lesion regions,involving damage to the multiple network regions.There are extensive connections between the cerebellum and the cerebral cortex,and the cerebellum plays an important role in cognition,attention,and the emotion.A large number of brain imaging research on epilepsy have found the abnormalities in multiple brain regions of the cerebellum,suggesting that cerebellar lesions are closely related to epileptic seizures,and the cerebellum may be involved in the integration and regulation of abnormal discharges in epilepsy.However,these studies have not characterized the abnormal patterns of the cerebellum in terms of macro-scale hierarchical organization with epilepsy.Therefore,this thesis aims to use the method of connectome gradient to elucidate the functional hierarchical organization of the cerebellum,and to explore the underlying structural basis behind it,so as to provide a new perspective for exploring the abnormal phenomenon of the cerebellum in epilepsy.In this thesis,the analysis method of multimodal brain imaging was used to verify the underlying neural mechanisms of the cerebellum of patients with GTCS,which mainly included two aspects.Firstly,we explored the disruption of the macroscopic connectome gradient patterns of the cerebellar cortex in patients with GTCS,and then by regression analysis of abnormal patterns and gene expression maps.It was found that there is a significant spatial correlation between abnormal patterns of connectomes gradient in cerebellum and gene expression,emphasized the role of the underlying transcriptome profiles information fusion and the abnormal functional hierarchical archetype in cerebellar.Furthermore,the results of gene enrichment analysis showed that genes with positive weights were mainly enriched in term related to cytokine regulation.Secondly,a morphological structural network was constructed based on the gray matter volume of the cerebellum subregion to detect the topological abnormalities in patients with GTCS.A regression model was established by integrating structural and functional connectivity to explore the atypical corresponding relationship of the function-structure network in the cerebellar with GTCS.The results showed that the structure-function correspondence was significantly different in the distribution of various regions of the cerebellum,and showed that the structure-function relationship were negatively significantly correlated with the connectome gradient in the healthy controls（HC）and patients with GTCS.Between-group comparisons discovered that consistently decreased structure-function corresponding associations in patients with GTCS,demonstrating that the structure-function relationships can characterize the cerebellar dysfunction and serve as an potential structural attribute of the connectome gradients.The result of the topological properties found that the global properties of cerebellar were characterized by the small-worldness in HC and patients with GTCS,but the shortest path length was decreased in patient with GTCS.At the same time,the alteration regions with local properties overlapped with the abnormal regions of structure-function corresponding relations and connectome gradients,and showed that the regional anomalies may be mediated the relationship between the aberrant pattern of the structure-function relationships and the connectome gradient in cerebellar,providing a key role for explaining the pathological mechanism of patients with GTCS.In conclusion,this thesis explores the underlying structural mechanisms and molecular basis based on the global compression of the connectome gradient in the cerebellar,finds the cognitive function,gene expression and anatomical foundation supporting the functional variation of the cerebellum GTCS,and further fully understands the pathophysiological principle of generalized epileptic seizures.