Resting-state Functional Magnetic Resonance And Metabolomics Study Of Meige Syndrome

Part 1:The exploration of altered degree centrality and functional connectivity in untreated Meige syndrome based on resting functional magnetic resonance imagingObjectives : Meige syndrome(MS)is characterized by abnormal functional activity in multiple brain regions,but its core brain regions and their interaction patterns remain unclear.This study proposes a resting attitude degree centrality(DC)approach to explore the core brain regions and functional network changes in MS patients in order to obtain imaging markers and explore the underlying pathogenesis.Methods: 51 untreated MS patients and 32 healthy individuals matched for age,sex,and years of education were enrolled in this study.All subjects underwent rsf MRI scans and clinical scale assessment.We used the degree centrality method to study the difference of DC between MS patients and healthy controls(HC).Pearson correlation analysis was used to explore the correlation between altered DC value and clinical features of MS.Support vector machine(SVM)was used to evaluate whether altered DC value of different brain areas could identify MS patients from controls.In addition,whole-brain functional connectivity(FC)analysis was performed using clinical feature-related differential brain regions as ROI.Results:(1)Compared with HCs,the DC values in the right thalamus,precuneus,median cingulate and paracingulate gyri,middle frontal gyrus,and the left inferior parietal,but supramarginal and angular gyri,and dorsolateral superior frontal gyrus were increased in the MS group,while the DC values of the left amygdala,heschl gyrus,superior temporal gyrus,and right inferior occipital gyrus,postcentral gyrus were decreased.(2)In the MS group,the DC value of the right thalamus was positively correlated with the Burke-Fahn-Marsden dystonia rating movement scale(BFMDRS-M)score(r=0.50,p=0.000),and the DC value of the right precuneus was positively correlated with BFMDRS-M(r=0.30,p=0.028)and Burke-Fahn-Marsden dystonia rating disability scale(BFMDRS-D)score(r=0.82,p=0.000).The DC value of the right medial frontal gyrus was positively correlated with the course of disease(r=0.44,p=0.001),the DC value of the left amygdala was negatively correlated with age(r=-0.56,p=0.000),and the DC value of the left superior temporal gyrus was negatively correlated with Hamilton Depression Scale score(r=-0.44,p=0.001).(3)The SVM results showed that 51 patients and 28 HCs were correctly classified.The combination of DC values in the right postcentral gyrus,left amygdala,right middle frontal gyrus,right inferior occipital gyrus,and left dorsolateral superior frontal gyrus could best distinguish patients from controls with sensitivity,specificity,and accuracy of 100%,87.50%,and 95.18%,respectively.(4)Using the right thalamus,the left amygdala,the right middle frontal gyrus,right precuneus,and the left superior temporal gyrus as ROIs for FC analysis,it was showed that the FC values between the right thalamus with bilateral middle frontal gyrus,and left middle temporal gyrus were increased in MS patients compared with the HC group.while the FC values between the left amygdala with the right inferior temporal gyrus,right putamen,and the left fusiform gyrus,the left superior temporal gyrus,the left dorsolateral superior frontal gyrus,and bilateral precuneus were decreased.In MS patients,the FC between the right middle frontal gyrus with the left inferior temporal gyrus,the right middle temporal gyrus,the right lingual gyrus,and the left paracentral lobule were increased,while the FC of the right precuneus and the right middle temporal gyrus,the right inferior frontal gyrus,opercular part,the right dorsolateral superior frontal gyrus,the precentral gyrus and the left inferior parietal,but supramarginal and angular,and the bilateral putamen were increased,and the FC of the left superior temporal gyrus and the right lingual gyrus,the right Rolandic operculum,the right median cingulate and paracingulate gyri and the left middle temporal gyrus,the left postcentral gyrus were decreased.Conclusion : MS patients have altered DC in several brain regions in resting state,mainly involving in default mode networks,executive networks,and sensorimotor integration functions.In addition,the combination of DC values in the right posterior central gyrus,the left amygdala,the right middle frontal gyrus,the right suboccipital gyrus and the left dorsolateral superior frontal gyrus can be used as potential imaging biomarkers to identify MS patients and healthy individuals.The results of this study may provide an imaging basis for exploring new therapeutic targets and mechanism for MS in the future.Part 2: The exploration of the mechanism and clinical efficacy prediction of botulinum toxin type A in the treatment of Meige syndrome based on resting functional magnetic resonance imagingObjectives:The efficacy of botulinum toxin type A(Bo NT-A)in MS varies widely among individuals,and its therapeutic mechanism is unclear.This study aims to explore the therapeutic mechanism of Bo NT-A from the perspective of resting state brain imaging,and clarify the predictive value of local brain functional activity under baseline state to the clinical efficacy of Bo NT-A in the treatment of MS,which is conducive to further understanding of the pathological mechanism of MS,and provides a basis for optimizing its efficacy.Methods: This study included 51 MS patients and 32 HCs,of whom 26 patients completed f MRI scans after Bo NT-A treatment.Regional homogeneity(Re Ho)and fractional amplitude of low frequency fluctuation(f ALFF)at baseline were used as image representation indicators,and Pearson correlation analysis was used to explore the correlation between Re Ho and f ALFF values in different brain regions and clinical characteristics in MS group.In addition,different brain regions related to clinical characteristics were selected as ROIs for whole-brain FC analysis to compare changes in brain functional networks before and after Bo NT-A treatment.Results:(1)The Re Ho values of the left putamen(r=0.43,p=0.000),the right posterior central gyrus(r=0.30,p=0.035)and the f ALFF values of the left precuneus(r=0.58,p=0.000)in MS patients were positively correlated with the improvement of the degree of movement disorder after Bo NT-A treatment.The f ALFF value of the right medial frontal gyrus(r=-0.40,p=0.001)was negatively correlated with improvement in the degree of dyskinesia after treatment.The Re Ho value of the left putamen(r=0.30,p=0.023)and the f ALFF value of the left precuneus(r=0.34,p=0.016)in MS patients were positively correlated with the improvement of depression degree,while the Re Ho value of the left dorsolateral superior frontal gyrus(r=-0.37,p=0.007),the f ALFF value of right apex gyrus(r=-0.34,p=0.016)was negatively correlated with the improvement of depression after treatment.(2)The fALFF value and ReHo value of the different brain regions were analyzed between therapeutic effect.The f ALFF values of the right angular gyrus and left precuneus of the Bo NT-A good efficacy group were higher than that of the poor efficacy group,and the Re Ho value of the right postcentral gyrus and the left putamen was also higher.ROC curve analysis showed that the area under the curve(AUC)of the f ALFF value in the right angular gyrus and left precuneus and the Re Ho value in the right postcentral gyrus and left putamen for predicting the poor efficacy of Bo NTA were 0.876,0.714,0.914 and 0.768,respectively.(3)The right middle frontal gyrus,the left precuneus,the left putamen,and the right postcentral gyrus were used as ROIs to conduct FC analysis of MS patients.The FC between the middle frontal gyrus with the right inferior frontal gyrus,opercular part,the right precuneus,the bilateral inferior temporal gyrus,the bilateral angular gyrus and the left orbital inferior frontal gyrus were increased after Bo NT-A treatment.The FC between the left precuneus with the right inferior temporal gyrus,the right middle temporal gyrus,the right putamen,the right globus pallidus,the left orbital middle frontal gyrus and orbital inferior frontal gyrus were increased.The FC between the left putamen with the right median cingulate and paracingulate gyri,the right supplementary motor area,the left globus pallidus,the left superior parietal were increased.Conclusion : The fALFF values of the right angular gyrus and left precuneus,and the Re Ho values of the right postcentral gyrus and left putamen may be imaging index for Bo NT-A efficacy prediction in MS patients.Bo NT-A can effectively treat MS,which may be related to improving the FC between motor cortex and frontotemporal lobe,but has no obvious effect on sensory cortex.Part 3: Study on pathological mechanism of Meige syndrome using resting brain functional magnetic resonance imaging and metabonomicsObjectives: MS is a rare movement disorder,but reliable diagnostic markers are still lacking,and its pathological mechanism is still unclear.In this study,metabolomics was used to explore the changes of plasma metabolites associated with MS,combined with f MRI technology to locate brain regions with abnormal functional activity,and further explore the underlying pathological mechanism and potential diagnostic indicators of MS.Methods: In this study,20 MS patients and 17 HCs were finally included.The differential metabolites of MS were systematically detected using LC-MS nontargeted metabolomics technology,and the pathway enrichment analysis of metabolites by KEGG was performed for the differential metabolites.Then,ROC curve analysis was used to explore the diagnostic value of differential metabolites in MS.The f ALFF values were extracted from different brain regions in MS patients,and personal correlation analysis was used to explore the correlation between abnormal zf ALFF values and differential metabolites.Results:(1)In this study,LC-MS was used to analyze the differential metabolite spectrum in the blood of patients with MS,and a total of 48 differential metabolites were found,including 22 ascending metabolites and 26 descending metabolites.By classifying these metabolites,the most abundant metabolites are mainly dispersed in two major categories:(1)lipids and lipid molecules;(2)Amino acids,peptides,and their analogues.(2)In this study,14 blood metabolites were screened out using the ROC curve for MS diagnosis,including testosterone sulfate,LPC 16:0,LPC 18:1,DHA,ketoleucine,arachidonic acid,glycine ursodeoxycholic acid,linoleic acid epoxide,hexylresorcinol,indole-3-acrylic acid,DL tryptophan,PC(18:2e/16:0),decanoyl carnitine,and Acar 10:1.(3)Correlation analysis was found that the value of fALFF in the right middle frontal gyrus of MS patients was negatively correlated with blood LPC16:0(r=-0.59,p=0.007)and ACar 10:1(r=-0.46,p=0.041).The value of f ALFF in the left medial superior frontal gyrus was positively correlated with blood LPC16:0(r=0.45,p=0.047).The value of f ALFF in the right posterior central gyrus was negatively correlated with blood LPC16:0(r=-0.46,p=0.043).The value of f ALFF in the left central posterior gyrus was negatively correlated with ACar 10:1(r=-0.47,p=0.038).The value of f ALFF in the left lower cerebellum was positively correlated with testosterone sulfate(r=0.58,p=0.007).Conclusions: Amino acid metabolism,lipid metabolism,and oxidative stress are closely related to the pathogenesis of MS,and the content of differential metabolites is related to functional activities in some brain regions.These results help to further elucidate the pathological mechanisms of MS.These results contribute to further elucidate the pathophysiological mechanism of MS.In addition,testosterone sulfate,LPC 16:0,LPC 18:1,DHA,ketoleucine,arachidonic acid,glycine ursodeoxycholic acid,linoleic acid epoxide,hexylresorcinol,indole-3-acrylic acid,DL tryptophan,PC(18:2e/16:0),decanoyl carnitine,and Acar 10:1 may be potential biomarkers for MS.