原发全面强直阵挛癫痫患者皮层-纹状体-丘脑-小脑网络的静息态功能MRI的对照研究

目的 探讨应用静息态功能MRI网络技术描绘原发全面强直阵挛癫痫 (IGE-GTCS)患者皮层-纹状体-丘脑-小脑网络的模式。方法 前瞻性纳入2009年7月—2016年10月IGE-GTCS患者60例为IGE-GTCS组,同时纳入与IGE-GTCS组患者年龄、性别相匹配的健康志愿者60名为正常对照组。两组受试者于3 T超导MR仪下行静息态功能MRI数据收集,采用北京师范大学脑影像处理分析软件DPARSF 4.4完成预处理。采用皮层分区模板,将整个大脑分成额叶皮层、运动皮层、感觉皮层、顶枕皮层、颞叶皮层5个感兴趣区域(ROI),自动解剖标记模板定义丘脑、纹状体(包括尾状核、壳核、苍白球)和小脑的皮层下结构,构建皮层-皮层下核团-小脑网络。分别计算5个皮层区域与皮层下核团体素间的功能连接系数,获得系数图;并将得到的相关系数通过Fisher Z 转换,符合正态分布的功能连接系数图用于后续统计分析。使用SPM 12软件的两样本t检验,对IGE-GTCS组与正常对照组间皮层-皮层下核团-小脑功能连接的异常进行比较,应用高斯随机场理论(GRF)进行多重比较校正,体素校正水平取P＜0.01,团块校正水平取P＜0.05,双尾校正;并将IGE-GTCS患者功能连接改变的区域与临床病程进行Pearson相关分析。结果 因头动过大, IGE-GTCS组排除5例,最终纳入55例,男35例、女20例,年龄(25.11±6.0)岁,病程(11.3±6.6)年;正常对照组共60名,其中男37名、女23名,年龄(26.38±6.5)岁。两组受试者年龄、性别差异均无统计学意义(t=1.086、χ²=0.048, P值均＞0.05)。相比于正常对照组,IGE-GTCS组功能连接结果差异均有统计学意义(GRF校正,体素水平P值均＜0.01、团块水平P值均＜0.05):(1)额叶皮层,与双侧小脑脚2区(左右半球体素分别为115、182, t值分别为-5.57、-3.82)、右侧苍白球(体素=28, t=-7.42)连接降低,与双侧丘脑(左右半球体素分别为121、134, t值分别为10.48、9.16)、尾状核(左右半球体素分别为206、199, t值分别为13.40、11.59)、壳核(左右半球体素分别为178、219, t值分别为7.29、8.79)及小脑4、5区(左右半球体素分别为55、45, t值分别为2.63、2.74)连接增加。(2)运动皮层,与左侧小脑脚1区(体素=98, t=-3.10)、双侧苍白球(左右半球体素分别为26、31, t值分别为-7.05、-6.86)连接降低,与丘脑(左右半球体素分别为137、145, t值分别为11.06、9.77)、尾状核(左右半球体素分别为202、197, t值分别为12.88、11.79)、壳核(左右半球体素分别为104、120, t值分别为7.54、10.71)、小脑4、5区(左右半球体素分别为64、43, t值分别为4.62、5.13)及小脑脚2区(左右半球体素分别为85、85, t值分别为4.23、4.23)连接增加。(3)感觉皮层,与左侧小脑脚1区(体素=103, t=-3.87)连接降低,小脑4、5区(左右半球体素分别为72、63, t值分别为4.58、5.96)、双侧小脑脚2区(左右半球体素分别为173、173, t值分别为4.22、4.22)、丘脑(左右半球体素分别为143、151, t值分别为10.41、7.91)、尾状核(左右半球体素分别为198、195, t值分别为10.30、8.82)、壳核(左右半球体素分别为105、110, t值分别为6.38、8.06)、苍白球(左右半球体素分别为8、9, t分别为4.95、4.31)连接增加。(4)顶枕皮层,与右侧苍白球(体素=23, t=-7.45)连接降低,与小脑4、5区(左右半球体素分别为32、28, t值分别为3.56、3.89)、左侧小脑脚2区(体素=15, t=4.56)、丘脑(左右半球体素分别为107、118, t值分别为10.57、10.62)、尾状核(左右半球体素分别为201、197, t值分别为7.52、8.43)及壳核(左右半球体素分别为112、164, t值分别为6.53、7.21)连接增加。(5)颞叶皮层,与右侧小脑4、5区(体素=29, t=6.35)、双侧小脑脚2区(左右半球体素分别为58、128, t值分别为4.66、2.77)、丘脑(左右半球体素分别为128、136, t值分别为10.32、10.48)、尾状核(左右半球体素分别为207、203, t值分别为10.88、10.31)及壳核(左右半球体素分别为134、157, t值分别为7.39、6.75)连接均增加。额叶皮层-左侧小脑8区、运动皮层-左侧小脑8区、感觉皮层-小脑蚓部6区、顶枕皮层-左侧小脑8区、颞叶皮层-右侧小脑脚2区功能连接与病程相关系数分别为-0.385、-0.455、-0.362、-0.332、-0.544,差异均有统计学意义(P值均＜0.01)。结论 IGE-GTCS存在广泛的皮层-纹状体-丘脑-小脑网络功能连接的异常,表现为特异核团的功能连接的增高与降低,部分功能连接的改变与病程呈负相关。

Resting state functional magnetic resonance imaging of cortical-striatum-thalamic-cerebellar network in patients with idiopathic generalized epilepsy with generalized tonic-clonic seizure

Objective To investigate the cortical-cortical-striatum-thalamus-cerebellum network in patients with idiopathic generalized epilepsy with generalized tonic-clonic seizure (IGE-GTCS), using resting-state fMRI functional connectivity analyses.Methods Prospective study included sixty patients with IGE-GTCS was condncted from July 2009 to October 2016 in Jinling Hospital of Medical School of Nanjing University. Sixty healthy volunteers were set as controls according to age and gender. Resting-state fMRI data were collected on a 3 T MR scanner. The preprocessing was completed by DPARSF 4.4 software of Beijing Normal University. The whole brain was divided into five regions of interest (ROI) including frontal cortex, motor cortex, sensory cortex, parieto-occipital cortex and temporal cortex. The subcortical structures including thalamus, striatum (including caudate nucleus, putamen and pallidum) and cerebellum were defined by automated anatomical labeling, and the cortico-subcortical nucleus-cerebellum network was constructed. The functional connectivity coefficients between five cortical regions and subcortical nuclides were calculated, and the coefficient maps were obtained. The correlation coefficients were transformed by Fisher Z transformation, and the functional connectivity coefficient maps conforming to normal distribution were used for subsequent statistical analysis. The functional connectivity changes of striatum, thalamus and cerebellum corresponding to different cortex areas were compared between the patients and controls by using two sample t-test. The functional connectivity changes of the patients were correlated with the clinical variable of epilepsy duration. Gauss random field (GRF) was used to perform multiple comparison correction, the voxel P＜0.01, cluster P＜0.05, double tail correction. Pearson correlation analysis was performed between the change of functional connectivity and the epilepsy duration in patients with IGE-GTCS.Results Five cases were excluded from the IGE-GTCS group because of excessive head movement. Fifty-five cases were eventually enrolled in the IGE-GTCS group, including 35 males and 20 females, aged (25.11±6.0) years and the duration of disease (11.3±6.6) years. Sixty cases in the control group, including 37 males and 23 females, aged (26.38±6.5) years. There was no significant difference in age and sex between the two groups (t=1.086, χ²=0.048,all P values >0.05). (1)Compared with the control group, the functional connectivity between the frontal cortex and subcortical areas were decreased in the bilateral cerebellar-crus 2 (cluster size:left=115, right=182; t=-5.57, -3.82) and the right pallidum (cluster size:28, t=-7.42) , while increased in the thalamus (cluster size:left=121, right=134; t=10.48, 9.16), caudate nucleus (cluster size:left=206, right=199; t=13.4, 11.59), putamen (cluster size:left=178, right=219; t=7.29, 8.79) and cerebellar-4-5 (cluster size: left=55, right=45; t=2.63, 2.74). (2)The functional connectivity between the motor cortex and subcortical areas were decreased in the left cerebellar-crus 1 (cluster size=98, t=-3.10) and the bilateral pallidum (cluster size: left=26, right=31; t=-7.05, -6.86), while increased in the thalamus (cluster size: left=137, right=145; t=11.06, 9.77), caudate nucleus (cluster size: left=202, right=197; t=12.88, 11.79), putamen (cluster size: left=104, right=120; t=7.54, 10.71) and cerebellar-4-5 (cluster size: left=64, right=43; t=4.62,5.13) and cerebellar-crus 2 (cluster size: left=85, right=85; t=4.23, 4.23). (3)The functional connectivity between the sensory cortex and the subcortical areas were decreased in the left cerebellar-crus 1 (cluster size=103, t=-3.87), cerebellar-4-5(cluster size: left=72, right=63; t=4.58, 5.96), bilateral cerebellar-crus 2(cluster size: left=173, right=173; t=4.22, 4.22), while increased in the thalamus (cluster size: left=143, right=151; t=10.41, 7.91), caudate nucleus (cluster size: left=198, right=195; t=10.30, 8.82), putamen (cluster size: left=105, right=110; t=6.38, 8.06), pallidum (cluster size: left=8, right=9; t=4.95, 4.31), cerebellar-4-5 (cluster size: left=72, right=63; t=4.58, 5.96) and cerebellar-crus 2 (cluster size: left=173, right=173; t=4.22, 4.22). (4)The functional connectivity between the parieto-occipital cortex and the subcortical areas were decreased in the right pallidum (cluster size: 23, t=-7.45), while increased in the cerebellar-4-5 (cluster size: left=32, right=28; t=3.56,3.89), left cerebellar-crus 2 (cluster size: 15; t=4.56), thalamus (cluster size: left=107, right=118; t=10.57,10.62), caudate nucleus (cluster size: left=201, right=197; t=7.52, 8.43) and putamen (cluster size: left=112, right=164; t=6.53, 7.21). (5)The functional connectivity between the temporal cortex and the subcortical areas were increased in the right cerebellar-4-5 (cluster size: 29, t=6.53), bilateral cerebellar-crus 2 (cluster size: left=58, right=128; t=4.66, 2.77), thalamus (cluster size: left=128, right=136; t=10.32, 10.48), caudate nucleus (cluster size: left=207, right=203; t=10.88, 10.31) and putamen (cluster size: left=134, right=157; t=7.39, 6.75). The correlation coefficients of functional connectivity with the epilepsy duration between frontal cortex and left cerebellum-8 was -0.385. The correlation coefficients of functional connectivity with the duration between motor cortex and left cerebellum-8 was -0.455. The correlation coefficients of functional connectivity with the duration between sensory cortex and vermis-6 was -0.362. The correlation coefficients of functional connectivity with the duration between parieto-occipital cortex and left cerebellum-8 was -0.332. The correlation coefficients of functional connectivity with the duration between temporal cortex and right cerebellar-crus 2 was - 0.544, with statistical differences (all P values＜0.01).Conclusions There are extensive abnormalities of cortical-striatum-thalamus-cerebellum network functional connections in IGE-GTCS, which presents increased and decreased functional connections of specific nuclei, and some functional connectivity changes are negatively correlated with the duration of disease.