| Generalized epilepsy is a functional brain disease caused by the abnormal synchronous firing of many neurons in both brain hemispheres.It involves brain cortices and subcortices,but its pathological mechanism is still unclear.Until now,the epilepsy has been widely considered as a disease of brain network.To better reveal the brain network pathomechanism related to epileptic electrical activity and cognitive impairment,it is essential to explore at the brain network level.Multimodal brain imaging techniques provide important supports for characterizing the multidimensional brain network in epilepsy.The interaction patterns of brain networks at different scales in epilepsy can be revealed by using the fusion analysis of multimodal brain imaging.This thesis used the multimodal brain imaging technology to explore the features of large-scale brain functional networks in generalized epilepsy and further focused on the interaction characteristics between subcortices and cortices.This thesis mainly included following five parts:1,For the classic thalamic-cortical circuit,we divided the thalamus into eight parts according the functional and structural connectivity between thalamus and cerebral cortex.Then,the functional connectivity between each thalamic subregion and each voxel of cerebral cortex was calculated to explore the common and specific alterations of functional interaction between different thalamic subregions and cortices in juvenile myoclonic epilepsy(JME).In patients,the posterior thalamus showed decreased functional connectivity with the superior frontal gyrus and enhanced functional connectivity with the supplementary motor areas,which might be related to the propagation of generalized spikes with frontocentral predominance in JME.Besides,increased thalamic functional connectivity with the salience network and reduced functional connectivity with the default mode network were observed,which might be responsible for the emotional and cognitive defects in patients.Enhanced functional connectivity in the basal ganglia and cerebellum suggested possible regulatory roles on the thalamo-cortical circuit.The present work provided evidence to understand that specific thalamic subregions contribute to the abnormalities of thalamic-cortical networks in epilepsy.Moreover,the posterior thalamus might play a crucial role in generalized epileptic activity.2,The default mode network plays a crucial role in the origin and propagation of epileptic activities as well as in consciousness and cognitive functions.Thus,it is necessary to elaborate the functional characteristics of default mode network in epilepsy.This work aims to investigate functional profiles of default mode network using a multicenter study,collecting 247 patients with generalized epilepsy,288 patients with focal epilepsy,135 patients with benign epilepsy,and 307 healthy controls.Voxel-wise and node-based analyses were calculated to investigate static and dynamic features of functional connectivity in the default mode network.Separate statistics was first performed in single centers and then coalesced to integrated statistical results across centers.Besides,we also performed analyses in various subtypes of epilepsies in single centers.In the voxel-wise functional connectivity analysis,except for the increased functional connectivity in dorsal posterior cingulum,decreased functional connectivity was observed in other default mode network regions in both generalized and focal epilepsy.In the node-based functional connectivity analysis,both generalized and focal epilepsy demonstrated decreased functional connectivity and increased variability of functional connectivity in default mode network.Notably,the benign epilepsy did not show significantly abnormal functional connectivity alterations of default mode network,which provided a new clue to understanding its benignity.The hypoconnectivity and hypervariability in default mode network across epilepsies might reflect a shared pathomechanism underlying the epileptogenesis and cognitive impairments.In general,these findings provide a reliable and comprehensive reference for future epilepsy studies.3,The current study constructed large-scale static and dynamic functional connectivity networks with structural connectivity as constraints by using multimodal MRI data.Moreover,resting-state BOLD time course was deconvolved to neural time course using a blind deconvolution method.Specifically,the network-level weighted coupling probability was proposed to evaluate the association between static and dynamic functional connectivity.The patients with generalized epilepsy showed abnormal alteration of multimodal connection features in the default mode network,subcortex network and frontoparietal network.Besides,antagonism between static and dynamic functional connectivity was observed in large-scale networks in healthy controls,while patients with generalized epilepsy showed significantly decreased antagonism in core epileptic networks.In sum,the present findings revealed distinct connective profiles in different epileptic networks and provided new clues to the brain network mechanism of epilepsy from the perspective of antagonism between dynamic and static functional connectivity.4,Using the functional connectivity density(FCD)measurement and the slidingwindow approach,we investigated spatiotemporal dynamic characteristics of functionality.Besides,we also comprehensively depicted spatiotemporal variability patterns of brain network and clarified the pathological characteristics of epileptic brain networks.For a given region,the standard variation of the FCD values across windows was calculated as the temporal variation of FCD(tv FCD)and the variation of voxel-wise spatial distribution was calculated as the spatial variation of FCD(sv FCD).In healthy controls,we found the higher-order networks showed the highest variation,the subcortical and primary networks showed moderate variation,and the limbic system showed the lowest variation.Relative to controls,the patients with generalized epilepsy showed weaken temporal and enhanced spatial variation in the default mode network and weaken temporospatial variation in the subcortical network.Besides,enhanced temporospatial variation in sensorimotor and higher-order networks was also observed in patients.The hyper-synchronization of specific brain networks was inferred to be associated with the phenomenon responsible for the intrinsic propensity of generation and propagation of epileptic activities.The disrupted dynamic characteristics of sensorimotor and higher-order networks might potentially contribute to the driven motion and cognition phenotypes in patients.In all,the present work shed light on the dynamics underlying neuropathological profiles of epilepsy.5,The hierarchical functional connectivity characteristics of subcortical regions in generalized epilepsy was investigated in this section.To demonstrate the specific patterns of generalized epilepsy,patients with temporal lobe epilepsy were included to perform further comparisons.A step-wise functional connectivity method was applied to the thalamus,striatum,and cerebellum to investigate the functional hierarchical architectures.Then,the connectivity intensity,link distance,and spatial scope were depicted and compared between groups.Subcortical structures gradually connected to a common set of cortical regions,locating in primary sensorimotor and fronto-parietal-attention networks.Common hypoconnectivity in the default mode network and hyperconnectivity in the visual network were revealed in both patient groups and specific hyperconnectivity in the precentral and postcentral gyri in generalized epilepsy.The subcortical structures of generalized epilepsy showed predominant prolonged distance with supplementary areas.Besides,the visual cortex showed prolonged distance with thalamus and striatum,and shortened distance with cerebellum in generalized epilepsy.In addition,patients with generalized epilepsy showed augmented scope in the visual network and the higher order network than healthy controls.This part provided novel evidence to reveal the diseasespecific pathological disturbance of cortical hierarchical connectivity of subcortical structures and highlighted that the sensory and perceptual system might be a notable point for understanding the subcortical effect in different types of epilepsy.Taken together,the current research work started from the multi-modal fusion of brain networks,and used the function-structure,dynamic-static,and time-space fusion analysis technology to reveal the multi-dimensional characteristics of the comprehensive epileptic brain network.The current work provided important information for exploring clinical pathological mechanism.The present results refined and expanded the traditional thalamic-cortical circuit,and clarified the pathological specificity of different circuits.Using big data research from multi-centers,we clarified the abnormal functional state of default mode network dominated by hypoconnectivity.The fusion analysis of large-scale brain network connections revealed the abnormality of the epileptic brain network with default mode network,subcortical and frontoparietal networks as the core,and the abnormal coupling relationship between dynamic and static connectivity.Moreover,the fusion of temporospatial characteristics of dynamic functional connectivity further pointed out specific change patterns of the dynamic characteristics of different brain networks in generalized epilepsy.Furthermore,the hierarchical network analysis method based on stepwise functional connectivity revealed the changes in the subcortical-cortical information interaction,and proposed the subcortical-perceptual system-specific hyperconnectivity feature in generalized epilepsy.In general,the research results of this thesis proposed an explanation framework of the pathomechanism in which subcorticalcortical interaction is the core loop.Besides,the default mode and frontoparietal networks were suggested to be the main pathological networks in generalized epilepsy. |
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