Resting state functional magnetic resonance imaging of cortical-striatum-thalamic-cerebellar network in patients with idiopathic generalized epilepsy with generalized tonic-clonic seizure
Xie Xinyu1, Xu Qiang1, Zhang Qirui1, Yang Fang2, Xu Yin1, Lu Guangming1, Zhang Zhiqiang1
1Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China; 2Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
Abstract: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.
谢心瑀, 许强, 张其锐, 杨昉, 徐银, 卢光明, 张志强. 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[J]. 中华解剖与临床杂志, 2019, 24(1): 32-38.
Xie Xinyu, Xu Qiang, Zhang Qirui, Yang Fang, Xu Yin, Lu Guangming, Zhang Zhiqiang. Resting state functional magnetic resonance imaging of cortical-striatum-thalamic-cerebellar network in patients with idiopathic generalized epilepsy with generalized tonic-clonic seizure. Chinese Journal of Anatomy and Clinics, 2019, 24(1): 32-38.
Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the international league against epilepsy: position paper of the ILAE commission for classification and terminology[J]. Epilepsia, 2017, 58(4): 522-530. DOI:10.1111/epi.13670
[2]
Wei HL, An J, Zeng LL, et al. Altered functional connectivity among default, attention, and control networks in idiopathic generalized epilepsy[J]. Epilepsy Behav, 2015, 46: 118-125. DOI:10.1016/j.yebeh.2015.03.031
[3]
Luo C, Li Q, Xia Y, et al. Resting state basal ganglia network in idiopathic generalized epilepsy[J]. Hum Brain Mapp, 2012, 33(6): 1279-1294. DOI:10.1002/hbm.21286
[4]
Kim JB, Suh SI, Seo WK, et al. Altered thalamocortical functional connectivity in idiopathic generalized epilepsy[J]. Epilepsia, 2014, 55(4): 592-600. DOI:10.1111/epi.12580
[5]
Wang Z, Lu G, Zhang Z, et al. Altered resting state networks in epileptic patients with generalized tonic-clonic seizures[J]. Brain Res, 2011, 1374: 134-141. DOI:10.1016/j.brainres.2010.12.034
[6]
Long L, Zeng LL, Song Y, et al. Altered cerebellar-cerebral functional connectivity in benign adult familial myoclonic epilepsy[J]. Epilepsia, 2016, 57(6): 941-948. DOI:10.1111/epi.13372
[7]
Yan CG, Zang YF. DPARSF: A MATLAB toolbox for “pipeline” data analysis of resting-state fMRI[J]. Front Syst Neurosci, 2010, 4: 13. DOI:10.3389/fnsys.2010.00013
[8]
Zhang D, Snyder AZ, Fox MD, et al. Intrinsic functional relations between human cerebral cortex and thalamus[J]. J Neurophysiol, 2008, 100(4): 1740-1748. DOI:10.1152/jn.90463.2008
[9]
Ji GJ, Zhang Z, Xu Q, et al. Identifying corticothalamic network epicenters in patients with idiopathic generalized epilepsy[J]. AJNR Am J Neuroradiol, 2015, 36(8): 1494-1500. DOI:10.3174/ajnr.A4308
[10]
Wang Z, Zhang Z, Jiao Q, et al. Impairments of thalamic nuclei in idiopathic generalized epilepsy revealed by a study combining morphological and functional connectivity MRI[J]. PLoS One, 2012, 7(7): e39701. DOI:10.1371/journal.pone.0039701
[11]
Blumenfeld H, McCormick DA. Corticothalamic inputs control the pattern of activity generated in thalamocortical networks[J]. J Neurosci, 2000, 20(13): 5153-5162. DOI: 10.1523/jneurosci.20-13-05153.2000
[12]
Meeren H, van Luijtelaar G, Lopes da Silva F, et al. Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory[J]. Arch Neurol, 2005, 62(3): 371-376. DOI:10.1001/archneur.62.3.371
[13]
Avoli M, Rogawski MA, Avanzini G. Generalized epileptic disorders: an update[J]. Epilepsia, 2001, 42(4): 445-457. DOI:10.1046/j.1528-1157.2001.39800.x
Zhang Z, Liao W, Chen H, et al. Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy[J]. Brain, 2011, 134(Pt 10): 2912-2928. DOI:10.1093/brain/awr223
[16]
Cheng L, Yang X, Zhi-Wei G, et al. Abnormal basal ganglia functional connectivity, in idiopathic generalized epilepsy[J]. J Electr Sci Technol, 2011, 9(3):278-284. DOI: 10.3969/j.issn.1674-862X.2011.03.015
[17]
Loddenkemper T, Pan A, Neme S, et al. Deep brain stimulation in epilepsy[J]. J Clin Neurophysiol, 2001, 18(6): 514-532. DOI: 10.1097/00004691-200111000-00002
[18]
Krauss GL, Koubeissi MZ. Cerebellar and thalamic stimulation treatment for epilepsy[J]. Acta neurochir Suppl, 2007, 97(Pt 2):347-356