无先兆偏头痛患者的脑灰质体积和静息态功能连接研究

Altered gray matter volume and resting-state functional connectivity in migraine patients without aura

目的应用基于体素的形态学测量(VBM)和静息态功能连接方法,探讨无先兆偏头痛(MwoA)可能的神经影像学机制。方法选择2020年9月至2023年6月在徐州医科大学第二附属医院神经内科就诊的MwoA患者25例作为MwoA组,招募22名志愿者组成健康对照组。收集两组的人口学、临床特征以及汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)、蒙特利尔认知评估量表(MoCA)评分结果;MwoA患者还接受了偏头痛残疾程度评估问卷、头痛影响测试问卷-6以及头痛视觉模拟评分评估。所有被试者均接受高分辨率3D-T 1和静息态功能磁共振成像扫描;应用SPM12软件,采取VBM方法比较两组被试者脑灰质体积(GMV)之间的差异;应用GRETNA软件,以解剖自动标记90脑图谱分区作为感兴趣区进行全脑功能连接计算,组间差异采用两样本t检验进行统计学分析。采用Pearson偏相关方法分析MwoA患者脑GMV及功能连接变化与患者临床特征及量表评分之间的相关性。结果两组被试者在年龄、性别、教育年限、HAMA、HAMD及MoCA评分上差异无统计学意义(均P>0.05)。MwoA患者的偏头痛残疾程度评估问卷得分为(8.86±4.55)分,头痛影响测试问卷-6得分为(50.27±6.35)分,头痛视觉模拟评分得分为(6.68±1.73)分。和健康对照相比,MwoA患者右侧额上回、右侧扣带回及左侧丘脑的GMV显著减少(均P<0.05,错误发现率校正)。此外,MwoA患者左侧丘脑与右侧楔叶、左侧舌回及双侧楔前叶之间的功能连接显著减弱,右侧丘脑与右侧楔叶、舌回及楔前叶之间的功能连接显著减弱;右侧楔叶与左侧楔前叶、右侧额上回之间的功能连接显著减弱;左侧舌回与双侧楔前叶之间的功能连接显著减弱,右侧舌回与右侧楔前叶、左侧额上回之间的功能连接显著减弱;左侧楔前叶与双侧额上回之间功能连接显著减弱,右侧楔前叶与右侧额上回之间功能连接显著减弱(edge P<0.001,component P<0.05,基于网络的统计校正,置换检验次数=2000)。在MwoA患者中,左侧丘脑与右侧楔叶之间的功能连接(z值)与病程呈显著负相关(r=-0.530,P=0.011)。结论MwoA患者存在右侧额上回、扣带回及左侧丘脑灰质体积的下降;同时MwoA患者丘脑与视觉皮质网络、默认模式网络之间的功能连接显著减弱,视觉皮质网络、默认模式网络、执行控制网络之间的功能连接显著减弱;这些脑结构和功能的改变,可能是中枢对疼痛刺激的敏感性和反应性下降的一种适应性改变,并可能成为MwoA重要的神经影像学机制。

Objective To investigate the underlying neuroimaging mechanism of migraine without aura(MwoA)by using methods of voxel-based morphometry(VBM)and resting-state functional connectivity(FC).Methods Twenty-five MwoA patients admitted to Department of Neurology,the Second Affiliated Hospital of Xuzhou Medical University from September 2020 to June 2023 were recruited as MwoA group,and 22 volunteers were recruited as healthy control(HC)group.Demographic,clinical characteristics,scores of Hamilton Anxiety Scale(HAMA),Hamilton Depression Rating Scale(HAMD)and Montreal Cognitive Assessment(MoCA)of all subjects were collected;MwoA patients also received Migraine Disability Assessment Questionnaire,Headache Impact Test-6 and headache Visual Analogue Scale assessments.All subjects underwent high-resolution 3D-T 1 and resting-state functional magnetic resonance imaging scanning.The SPM12 software was used to compare the difference in gray matter volume(GMV)between the 2 groups by VBM method.The GRETNA software was adopted to calculate the whole brain FC with anatomical automatic labeling 90 as the regions of interest,and the difference in FC between the 2 groups was statistically analyzed by two-sample t-test.Pearson partial correlation was used to analyze the correlation between brain GMV and FC changes and clinical features and scale scores of MwoA patients.Results There existed no statistically significant difference between the 2 groups in age,gender,education,scores of HAMA,HAMD and MoCA(all P>0.05).Migraine Disability Assessment Questionnaire,Headache Impact Test-6 and headache Visua Analogue Scale scores of MwoA patients were(8.86±4.55),(50.27±6.35)and(6.68±1.73).Compared with the HC group,GMV was significantly decreased in the right superior frontal gyrus(SFG),right cingulate gyrus(CG)and left thalamus in the MwoA group(P<0.05,false discovery rate corrected).In addition,the MwoA group showed decreased FC between left thalamus and right cuneus,left lingual gyrus(LG)and bilateral precuneus;decreased FC between right thalamus and right cuneus,right LG and right precuneus;decreased FC between right cuneus and left precuneus and right SFG;decreased FC between left LG and bilateral precuneus,decreased FC between right LG and right precuneus and left SFG;decreased FC between left precuneus and bilateral SFG,and between right precuneus and right SFG(edge P<0.001,component P<0.05,network-based statistics correction,interation=2000).In MwoA patients,the FC(z-value)between left thalamus and right cuneus was negatively correlated with the duration of disease(r=-0.530,P=0.011).Conclusions MwoA patients showed decreased GMV in right SFG,CG and left thalamus.In MwoA patients,FC between thalamus and visual network(VN)and default mode network(DMN)was significantly decreased,and FC among VN,DMN and executive control network was significantly decreased.These changes in brain structure and function may be an adaptive change in the central sensitivity and responsiveness to pain stimuli,and may be an important neuroimaging mechanism of MwoA.