Research On The Relationship Between Brain Network Abnormalities And Transcriptomics In Medial Temporal Lobe Epilepsy

Epilepsy is a chronic neurological disorder characterized by recurrent,involuntary convulsions accompanied by unconsciousness.More than 70 million people worldwide suffer from epilepsy,and most of them are not properly treated.Epilepsy has become a public health imperative.Medial temporal lobe epilepsy（m TLE）is a common focal drug-refractory epilepsy.Existing studies consider medial temporal lobe epilepsy to be a network abnormality,but the pathogenesis behind it is still not well understood.The development of magnetic resonance imaging has provided us an effective way to investigate the pathogenesis of various neurological diseases.Moreover,as transcriptomic technology is becoming mature,we can obtain information about regional gene expression.Therefore,by effectively combining magnetic resonance imaging technology and transcriptome technology,we can study the neural mechanism of brain network abnormalities in patients with medial temporal lobe epilepsy from macroscopic large-scale to micromolecular level.First,we explored the functional abnormalities in the temporal cortex of m TLE patients based on functional MRI data from 74 m TLE patients and sex-age matched 74healthy controls.We utilized a new diffusion map embedding technique to obtain the principal functional gradient axis based on the functional connectivity between the temporal lobe and the cortex.We found that the temporal cortex functional gradient axis runs along the medial temporal lobe to the lateral temporal lobe.The functional gradient of m TLE was significantly increased in the fusiform gyrus and significantly decreased in the middle temporal gyrus and inferior temporal gyrus(P_FDR<0.05).The brain regions where functional gradient was significantly altered appeared precisely at the two endpoints of the functional gradient axis.Moreover,we found m TLE patients showed a compression of the principal functional gradient.Further,we used partial least squares regression models to find the weighted gene expression component which is most associated with functional differences in m TLE patients.The subset of genes with higher weights was mainly enriched in biological processes such as regulation of chemical synaptic transmission,modulation of neuronal projection development(P_FDR<0.05),and in neurons of cortex.This study provides a theoretical basis for understanding the relationship between function and gene expression in m TLE patients.Next,we used structural MRI data from 79 m TLE patients and gender-age matched77 healthy controls to explore structural abnormalities in morphologically similar networks in m TLE patients.The morphological similarity network can indirectly reflect structural connections between the cerebral cortex.Similar to previous findings,we found low values of morphological similarity network in primary cortex and high values of morphological similarity network in association cortex,which reflects the hierarchical structure of the brain.Further we found significantly lower mean morphological similarity network values in the parahippocampal gyrus of m TLE patients(P_FDR<0.05).Combined with the relationship between abnormal brain network structure and transcriptome,we found that a subset of genes with higher weights were mainly enriched in cation-gated pathways(P_FDR<0.05).The results of this study provide some complement to the biological pathways associated with functional network abnormalities.In summary,this thesis combines imaging and transcriptomics to study the brain network characteristics of patients with medial temporal lobe epilepsy from both functional and structural aspects,supporting the theory that medial temporal lobe epilepsy is a brain network abnormal disease.Further,it was found that brain network abnormalities in medial temporal lobe epilepsy may be related to biological processes such as synaptic transmission and ion transport and cortical neuronal cells.Our research provides a theoretical basis for exploring the pathogenesis and precision treatment of epilepsy patients.