| Epilepsy is a common chronic disease of the nervous system.It is a brain disease with neural dysfunction caused by highly abnormal synchronous firing of neurons,involving multiple brain functional systems,with distinct manifestations of abnormal brain networks.Epilepsy networks participate in the generation and transmission of epilepsy diseases,which is closely related to multi-dimensional clinical characteristics.The current understanding of the mechanism of epilepsy development has weakened the "focal" attribute of epilepsy,highlighted the network attribute of epilepsy,emphasized that epilepsy is a neurological disease that originates from abnormal discharges of local brain networks and spreads to other brain regions dynamically,and considered that epileptic brain networks are actually cortical and subcortical brain regions with functional and structural connectivity.The activity of any part of the network will cause the reaction of other structures.Epileptic brain network is very important for understanding the spatiotemporal structure and conduction pathway of epileptiform discharge activity.Temporal lobe epilepsy is a representative intractable epilepsy,and the neural network research on its occurrence and development has attracted much attention.Temporal lobe seizures are the result of complex multi brain region interaction,but the functional connectivity changes of brain regions and the role of specific brain regions in seizure and transmission are still unclear,and need to be further explored.In recent years,with the continuous progress of neuroimaging technology and brain network analysis technology,especially the rapid onset of blood oxygen dependent functional magnetic resonance imaging and diffusion tensor imaging,a new window has been opened for the study of brain mechanism of neuropsychiatric diseases.Because previous studies were mostly based on single-mode imaging technology to reflect single brain features,the fusion of multi-mode imaging technology is of great significance for describing the structural and functional network features of epilepsy and exploring the brain mechanism of seizure origin and network transmission.In this study,in order to avoid the interference of structural abnormalities caused by different etiologies on the electrical transmission network,we selected MRI negative temporal lobe epilepsy patients as the research objects.We used emerging magnetic resonance imaging technology and comprehensively applied various brain network analysis methods such as voxel morphological analysis,spatial statistical analysis of cellulose,functional connection density,local consistency,low-frequency amplitude,graph theory,etc.to explore the brain microstructure and epilepsy network of temporal lobe epilepsy,The brain network mechanism of temporal lobe epilepsy was explored comprehensively from the change of structural network parameters and the connection characteristics of functional networks.Part one:morphological study of gray matter in nonlesional temporal lobe epilepsyObjective:To study the characteristics of brain microstructural changes in temporal lobe epilepsy patients by using voxel based morphometry(VBM)to measure the gray matter of the whole brain in MRI negative temporal lobe epilepsy patients.Methods:selected epileptic patients who were hospitalized and outpatients in the Department of Neurology of our hospital from June 2018 to December 2021 and had no abnormality in the 3.0T MRI scan of the skull.All epileptic patients were diagnosed according to the diagnostic criteria of the 2017 International League Against Epilepsy(ILAE);According to the history,clinical symptoms and EEG changes,the patients with medial temporal lobe epilepsy were selected as the subjects of temporal lobe epilepsy research;The healthy people who were examined in the physical examination center of our hospital at the same time were selected as the healthy control group.The clinical data of the two groups of subjects were recorded in detail;High resolution 3D-MRI images were obtained by scanning the whole brain fast gradient echo sequences of the two groups of subjects.The image data were analyzed by VBM processing technology based on spm12 software package,and relevant statistical analysis was performed by spss25.0.Results:The study was divided into two groups:MRI negative temporal lobe epilepsy group and healthy control group.2.Fifty patients with medial temporal lobe epilepsy were included,including 28 females(56%)and 22 males(44%);The age ranged from 16 to 52 years old,with an average age of 35 years.30 healthy controls,including 16 females(53%)and 14 males(47%);The age ranged from 24 to 49 years old,with an average age of 33 years.After statistical analysis of the demographic information and clinical data of the two groups,there was no statistical difference between the epilepsy group and the healthy control group in gender,age and Education(P>0.05).2.The clinical data of patients with MRI negative temporal lobe epilepsy were analyzed.The results showed that the average age of onset was 21.27 ±15.13;Among them,there were 24 cases of right temporal lobe epilepsy and 26 cases of left temporal lobe epilepsy,with a similar proportion.35%of the patients had a previous history,of which 12%had a history of mild brain injury,the most common;The course of disease is 1-27 years,with a large span,with the most in 6-10 years,accounting for 42%,;66%of the patients had an attack frequency of less than 1 time/month,and there were more than two types of attacks.84%of the patients had an attack aura,74%of the patients were treated with single drug,and 26%of the patients were treated with multiple drugs.3.Comparing the gray matter volume of the MRI negative temporal lobe epilepsy group with the healthy control group,VBM showed that the gray matter volume of the temporal lobe epilepsy group decreased in different degrees in the right insula,the right orbital inferior frontal gyrus,the right marginal superior gyrus,the left occipital middle gyrus,the left occipital inferior gyrus,and the bilateral hippocampus.The total gray matter volume of the epilepsy group was significantly smaller than that of the healthy control group,and the difference was statistically significant(P<0.01).4.In temporal lobe epilepsy group,VBM of cerebral gray matter in left cerebellum(r=-0.5587,P<0.0001),right hippocampus(r=-0.5831,P<0.0001),left hippocampus(r=-0.4055,P=0.0035)and left middle occipital gyrus(r=-0.4744,P=0.0005)was negatively correlated with the course of epilepsy,while changes in other brain regions were not correlated with the course of epilepsy.Conclusion:1.The patients with temporal lobe epilepsy have extensive cortical atrophy,and the longer the course of disease,the more obvious the decrease of gray matter volume in the relevant brain area.2.The cortical changes of temporal lobe epilepsy patients are specific,which may be useful for revealing the epilepsy network.Part two:the study of brain structure network in nonlesional temporal lobe epilepsyObjective:To observe the structural changes of white matter fibers in the whole brain of temporal lobe epilepsy patients with MRI negative by using diffusion tensor imaging(DTI)and trace based spatial statistics(TBSs),and to evaluate the value of DTI parameters FA and MD in evaluating the damage of white matter microstructure in epilepsy patients.Explore the association between the underlying pathophysiological mechanism of epileptic brain white matter microdamage and epileptic structural networks.Methods:the selection of subjects was the same as that in the first part.An 8-channel phase array coil is used to receive NMR signals.T1WI,T2WI and flair scans were performed before DTI data acquisition to exclude brain diseases.DTI data acquisition adopts single shot spin echo plane echo sequence,which is parallel to the front and back of the brain to obtain whole brain axial diffusion plus imaging,and the obtained data is analyzed by TBSs.Results:1.Compared with the control group,the FA value of temporal lobe epilepsy group decreased in the left cingulate,right cingulate,left fornix and left inferior longitudinal bundle,and there was no area with increased FA value.The MD value increased significantly in bilateral anterior thalamic radiation,frontal forceps,right inferior longitudinal tract,left superior longitudinal tract,left uncinate tract,left fronto occipital tract and left corticospinal tract,and there was no area where the MD value decreased.2.In temporal lobe epilepsy group,FA values of left cingulate(r=-0.5011,P=0.0002),right cingulate(r=-0.5916,P<0.0001)and left fornix(r=-0.4777,P=0.0005)were negatively correlated with the course of epilepsy,while other brain regions were not.The MD values of left anterior thalamic radiation(r=0.7001,P<0.0001),right inferior longitudinal bundle(r=0.6209,P<0.0001)and left superior longitudinal bundle(r=0.6562,P<0.0001)were positively correlated with the course of epilepsy,while the other brain regions were not.Conclusion:1.The white matter microstructure of Tel brain is diffusely damaged,and the white matter injury is lateralized.Whether it is left TLE or right TLE,the left injury is more common;The degree of injury increased with the prolongation of the course of disease.2.Multiple brain structural networks of MRI negative epileptic patients were damaged,mainly involving limbic system,thalamic cortical loop,Papez loop and default network mode.3.DTI can effectively and non invasively observe the changes of brain white matter microstructure..Part three:the study of the topological properties of brain functional network in nonlesional temporal lobe epilepsyObjective:To study the topological properties of brain functional network in MRI negative temporal lobe epilepsy patients.Methods:the selection of study subjects and the collection of clinical data are the same as those in the first part.The epileptic structural network was constructed by relying on the image parameters of DTI to study the spontaneous activity of brain neurons and the changes of topological properties of brain spatial network in MRI negative temporal lobe epilepsy patients at rest,analyze the significance of the changes of "small world" properties of epileptic network,and explore the pathophysiological mechanism of abnormal changes of epileptic brain network topology in tel-nl and the association with epileptic functional network.Results:1.After multiple comparison check,the small world index between tle-nl patients and healthy controls(σ)、There was no significant difference in global efficiency(eg)and local efficiency(eloc).2.Compared with the control group,the node efficiency of the right inferior parietal corner gyrus in the MRI negative temporal lobe epilepsy group was higher,but the node efficiency of the right inferior parietal corner gyrus was lower;The clustering coefficients of nodes in left parahippocampal gyrus,middle temporal gyrus and right middle temporal gyrus decreased;The local efficiency of the nodes of the right insular lobe increased,and the local efficiency of the nodes of the bilateral middle temporal gyrus decreased;The shortest path length of nodes in left parahippocampal gyrus,middle temporal gyrus and right middle temporal gyrus increased;The node centrality of the right inferior parietal gyrus decreased,and the node centrality of the left superior marginal gyrus increased.3.In tle-nl group,the functional connectivity of right inferior frontal gyrus left thalamus,right inferior frontal gyrus left thalamus,left caudate nucleus right thalamus,right inferior frontal gyrus right thalamus,right lenticular putamen right thalamus,right insula left globus pallidus,right lenticular putamen left thalamus,and right lingual gyrus right thalamus decreased compared with the healthy group.Conclusion:1.The "small world" attribute of tle-nl patients still exists,but its characteristics of high efficiency have been reduced.2.The topological properties of nodes in tle-nl patients have changed,and the abnormal brain regions are mainly located in the default network,suggesting that tle-nl patients have specific changes in brain functional networks.3.The functional connection between some brain regions and thalamus in tle-nl patients is reduced,which reveals that thalamus may be an important breakthrough in studying the cognitive and emotional changes of tle-nl patients.Part four:the study of brain function network in nonlesional temporal lobe epilepsyObjective:using resting state functional magnetic resonance imaging(RS fMRI)combined with functional connectivity density(FCD),local consistency(ReHo),low-frequency amplitude(Alff)and other brain function analysis methods to observe the changes of brain functional status and brain functional network in temporal lobe epilepsy patients with MRI negative at rest,to explore the correlation between the characteristics of brain functional activity and clinical manifestations of temporal lobe epilepsy in interictal period,and to deepen the understanding of epilepsy functional network.Methods:the selection of study subjects and the collection of clinical data are the same as those in the first part.Bold data acquisition adopts gradient echo plane echo sequence(EPI),which is parallel to the anterior and posterior combined whole brain axial imaging.Rest software was used to analyze the functional connection density(FCD),local consistency(ReHo)and low-frequency amplitude(Alff)of data lines.Results:1.Results of ReHo data analysis;In temporal lobe epilepsy group,the local consistency of left middle frontal gyrus,left lenticular nucleus and right lenticular nucleus was lower than that of the control group,and the ReHo value of left medial superior frontal gyrus,right inferior parietal corner gyrus and left paracentral lobule was higher than that of the control group.2.The FCD of MRI negative temporal lobe epilepsy patients was statistically analyzed,and it was found that there was no significant difference in short-term functional connectivity density between the two groups;The statistical results of the long-term functional connection density between the two groups showed that the long-term functional connection density of the temporal lobe epilepsy group was decreased in the right middle frontal gyrus and bilateral lenticular putamen,and significantly increased in the right anterior central gyrus,the right posterior central gyrus,the left superior parietal gyrus,the left inferior parietal corner gyrus and the left precuneus compared with the normal group.3.Compared with the control group,the areas with decreased Alff value in temporal lobe epilepsy group include right suboccipital gyrus,right lingual gyrus,left insular page and left middle occipital gyrus.The areas with decreased falff value include left middle temporal gyrus,left fusiform gyrus,left inferior temporal gyrus,left parahippocampal gyrus and left thalamus.Compared with the control group,the brain areas with increased Alff value in epilepsy group include right triangular subfrontal gyrus,left angular gyrus,left medial superior frontal gyrus,right dorsolateral superior frontal gyrus Right dorsolateral superior frontal gyrus and left supplementary motor area.The brain areas with increased falsf include right middle frontal gyrus,right posterior central gyrus,left superior parietal gyrus and left precuneus lobe.4.The correlation analysis between the course of epilepsy and ReHo value,FCD value,falff value and Alff value showed that the ReHo value of left middle frontal gyrus(r=-0.5011,P=0.0002)in temporal lobe epilepsy group was negatively correlated with the course of epilepsy,while the other brain regions were not correlated with the course of epilepsy.The FCD value of the right middle frontal gyrus(r=0.7001,P<0.0001)was negatively correlated with the course of epilepsy,while the other brain regions were not correlated with the course of epilepsy.The Alff value of the left medial superior frontal gyrus(r=0.7001,P<0.0001)was positively correlated with the course of epilepsy,while the other brain regions were not.The value of falff in the left thalamus(r=0.7001,P<0.0001)was negatively correlated with the course of epilepsy,while the other brain regions were not correlated with the course of epilepsy.Conclusion:1.There are multiple brain regions with abnormal ReHo,FCD,Alff and falff in tle-nl patients’ brains,suggesting that the intensity,consistency and functional network connection of neuronal activities in the corresponding brain regions have changed,indicating that long-term abnormal epileptic activities will cause extensive neurological damage.2.The extensive abnormal changes of brain function in tle-nl patients may be the pathological basis of their complex clinical manifestations.Among them,the abnormal changes of neural function in the limbic system brain area suggest that Tel may spread through the limbic system.The functional changes of the lenticular putamen indicate that the basal ganglia thalamus plays a key role in the process of epilepsy.The functions of multiple brain regions in the default network have changed,which indicates that the lesions of the brain functional network have an important connection with the occurrence of epilepsy.3.The combined application of multiple fMRI data analysis methods can effectively evaluate the changes of brain functional networks,help to explore the damage of epileptic networks and neural circuits,and improve the accuracy and sensitivity of localization diagnosis of epileptic foci. |
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