Multi-dimensional Brain Imaging Profiles Of Generalized Epilepsy

Generalized epilepsy is a common epileptic syndrome characterized by generalized seizures involving simultaneous discharge in both hemispheres of the brain.There is no significant lesion observed in clinical structural magnetic resonance imaging(MRI)scans.The pathological mechanisms of generalized epilepsy remaining unclear.The etiology of generalized epilepsy involves various factors,including genetic,structural,and metabolic,but their relationship with imaging profiles remains unclear.Better understandings of epilepsy brain structural and functional abnormalities can be achieved through crossmodal analysis.Multimodal MRI provides robust representations for quantifying epilepsy structural and functional features,laying the imaging foundation for multidimensional,multimodal brain information correlation.Relating structural and functional imaging characteristics based on multimodal brain imaging with multidimensional brain information such as transcriptomics,cell,and myelin architecture,this dissertation comprehensively explored the molecular neuro mechanisms and mesoscopic anatomical basis of generalized epilepsy.And proposing a new measure to characterize multi-faceted brain network topology,introducing a new perspective for understanding the cortical neural circuits and pathological mechanisms of generalized epilepsy.The main work of this dissertation includes the following two parts:1.Mapping the multi-faceted functional similarity gradient in cerebral cortex.Functional similarity gradient is proposed based on the concept of connectivity gradient.This gradient aggregates multi-faceted functional activity features,including local spontaneous oscillation and global network properties.Functional similarity gradient is closely linked with multiscale,multimodal brain structural representations.Functional similarity gradient exhibit specific correlation patterns with microscopic and mesoscopic structural information such as gene expression and laminar thickness,and these correlation patterns are consistent across different scales that all indicating the dominant role of granular and infragranular layers.The geometric framework of dual origin theory which developed from cyto-and myeloarchitecture captures the functional similarity gradient,demonstrating the inherent connection between macroscopic functional topology and mesoscopic structural principles,and providing new perspectives and insights understanding the structural basis of brain function and structural-functional coupling relationships.2.Abnormal representation of functional similarity gradient and transcriptomic mechanisms in generalized epilepsy.Based on the proposed functional similarity gradient measurement,a systematic examination of the gradient abnormalities in generalized epilepsy at the parcel level is conducted.The abnormal patterns of generalized epilepsy exhibit a gradient trend from unimodal primary regions to multimodal associative regions,with statistically significant differences distributed spatially,involving multiple functional networks.Through correlation analysis with transcriptomics,it is found that gradient abnormalities are closely related to ion pathways and exhibit close connections with disease pathways associated with epilepsy seizures.These results provide new knowledge for understanding the functional topological disorder of epilepsy,and through transcriptomics information,reveal potential molecular neuro mechanisms of generalized epilepsy.3.Abnormal representation of cortical connectome gradient in generalized epilepsy.This part systematically delineates the abnormal patterns of connectome gradient in epilepsy,systematically showing the abnormalities of epilepsy at different spatial scales that pronounced in default mode network and frontoparietal network.Gradient abnormalities also correlate with pathological characteristics such as disease duration.Unlike previous graph theory-based discrete functional network analysis,this part provides a low-dimensional representation of the functional topology for epilepsy,and offers a novel perspective for understanding epilepsy connectivity abnormalities.4.Morphological abnormalities of subcortical nuclei in generalized epilepsy and potential underlying neurotransmitter pathways.This part utilized shape morphological processing pipeline which has better ability to detect structural susceptibility to map the subtle structural damage in subcortical nuclei.The results show that all subcortical nuclei exhibit morphological abnormalities,with thalamus,striatum,and hippocampus being the significantly affected regions.Subsequently,neurotransmitter features are transformed into shape surface space,and correlating with morphological susceptibility to explore the molecular mechanisms.The results indicate that acetylcholine and adrenergic receptor expression are closely related to morphological damage.This part provides a comprehensive description of morphological damage in subcortical nuclei,and identifies neurotransmitter pathways related to epilepsy pathological mechanisms,which may contribute to the development of novel anti-epileptic medicines and the locating of precise neuromodulation.In summary,this dissertation which focusing on multi-dimensional,and multimodal research systematically explores the structural and functional abnormalities of generalized epilepsy,and integrates multiscale brain representations such as transcriptomics and cyto-and myeloarchitecture to investigate the underlying molecular and neural mechanisms.