Research of brain small-world network in children with Tourette syndrome

doi:10.3877/cma.j.issn.1673-5250.2018.02.002

Objective

To investigate the characteristics of brain small-world network in children with Tourette syndrome (TS) and the relationship between TS regional network features and clinical symptoms by resting state functional MRI (rs-fMRI).

Methods

From September 2015 to August 2017, a total of 25 cases of children who were diagnosed as TS in the West China Second University Hospital of Sichuan University were recruited as the study group. And 22 healthy children for physical examination were selected during the same period in the same hospital as the control group. The rs-fMRI data of subjects in two groups were collected and analyzed by GRETNA software to get brain regions with differences between whole brain and regional network properties. The correlation analysis of these clinical data was carried out. Chi-square test was used to compare the constituent ratio of gender of subjects between two groups. Independent-samples t test was used to compare the age of subjects between two groups. Wilcoxon rank sum test was used to compare the years of education of subjects between two groups. Non-parametric permutation test was used to compare the parameters of whole brain and local network of subjects between two groups. Linear correlation analysis was used to analyze the correlation between the area under curve (AUC) in the brain area with decreased node efficiency (e) and the Yale Comprehensive Symptom Scale (YGTSS) score. This study was approved by the Ethics Committee of Human Beings in West China Second University Hospital of Sichuan University and the guardians of every subject signed informed consent of clinical research.

Results

① There were no significant differences between two groups among the constituent ratio of gender, age, education years and other general clinical data (P>0.05). ② The results of the YGTSS scores of the study group were as follows, the motor tic total score was (13.32±2.94) scores, phonic tic total score was (4.84±5.10) scores, YGTSS total score was (42.16±12.59) scores. ③ The whole brain network of subjects in study group and control group both exhibited small-world network properties. Compared with control group, global efficiency (Eglob) in study group was significantly lower (P=0.014 1), characteristic path length (Lp) and standardized characteristic path length (λ) in study group were both significantly longer (P=0.008 2, 0.035 7), and all the differences between two groups were statistically significant, respectively. The e of left posterior cingulate gyrus (PCC) of study group was significantly lower than that of control group (P<0.000 1), and the e of the right putamen of study group was also significantly lower than that of control group (P=0.000 3), and both the differences between two groups were statistically significant, respectively. The above data of e between two groups were corrected by false positive rate (FDR). ④ In study group, there was a negative correlation between the AUC value of left operculum of gyrus frontalis inferior with decreased e and the YGTSS total score (r=-0.444 3, P=0.026 1), and the AUC value of right temporal pole with decreased e was also negatively correlated with the YGTSS total score (r=-0.462 2, P=0.020 0).

Conclusions

This study reveals that global brain network of children with TS has small-world network properties, but its whole brain and nodal neural network properties are different from healthy children with decreased Eglob, increased Lp and λ, which tends to switch to regular network. The nodal abnormal regions of the neuronal network in children with TS locate in the cerebral cortex-striatum-thalamic-cerebral cortex (CSTC) loop, revealing the characteristics of brain network. It provides whole brain network biomarker to assess the disease status and treatment of children with TS.

Key words: Tourette syndrome, Resting state functional magnetic resonance imaging, Small-world network, Child

表1 2组受试儿一般临床资料比较

组别	例数	性别[例数(%)]		年龄(岁，±s)	受教育年限[年，M(P₂₅～P₇₅)]
组别	例数	男	女	年龄(岁，±s)	受教育年限[年，M(P₂₅～P₇₅)]
研究组	25	19(76.0)	6(24.0)	8.4±2.0	2(1～3)
对照组	22	16(72.7)	6(27.3)	8.5±2.3	2(1～3)
检验值	?	χ²＝0.066 0		t＝－0.232 8	Z＝－0.219 1
P值	?	0.797 3		0.816 9	0.826 6

表1 2组受试儿一般临床资料比较

组别	例数	性别[例数(%)]		年龄(岁，±s)	受教育年限[年，M(P₂₅～P₇₅)]
组别	例数	男	女	年龄(岁，±s)	受教育年限[年，M(P₂₅～P₇₅)]
研究组	25	19(76.0)	6(24.0)	8.4±2.0	2(1～3)
对照组	22	16(72.7)	6(27.3)	8.5±2.3	2(1～3)
检验值	?	χ²＝0.066 0		t＝－0.232 8	Z＝－0.219 1
P值	?	0.797 3		0.816 9	0.826 6

图1 抽动秽语综合征患儿全脑节点效率减低的脑区位置示意图

表2 2组受试儿全脑及局部网络属性参数的曲线下面积比较(±s)

组别	例数	Eglob	Eloc	Cp	γ	λ	Lp	σ	左侧PCC的e	右侧壳e
研究组	25	0.128±0.008	0.176±0.008	0.136±0.013	0.439±0.078	0.262±0.010	0.465±0.035	0.400±0.077	0.101±0.032	0.118±0.021
对照组	22	0.133±0.005	0.179±0.008	0.133±0.014	0.461±0.053	0.257±0.007	0.441±0.018	0.428±0.052	0.136±0.014	0.140±0.012
P值	?	0.014 1^a	0.159 7	0.295 9	0.172 2	0.035 7^a	0.008 2^a	0.111 6	<0.000 1^b	0.000 3^b

表2 2组受试儿全脑及局部网络属性参数的曲线下面积比较(±s)

组别	例数	Eglob	Eloc	Cp	γ	λ	Lp	σ	左侧PCC的e	右侧壳e
研究组	25	0.128±0.008	0.176±0.008	0.136±0.013	0.439±0.078	0.262±0.010	0.465±0.035	0.400±0.077	0.101±0.032	0.118±0.021
对照组	22	0.133±0.005	0.179±0.008	0.133±0.014	0.461±0.053	0.257±0.007	0.441±0.018	0.428±0.052	0.136±0.014	0.140±0.012
P值	?	0.014 1^a	0.159 7	0.295 9	0.172 2	0.035 7^a	0.008 2^a	0.111 6	<0.000 1^b	0.000 3^b

图2 研究组25例抽动秽语综合征患儿的全脑节点效率减低脑区节点效率的AUC值与YGTSS总评分相关性分析(图2A：左侧岛盖部额下回e减低区e的AUC值与YGTSS总评分呈负相关关系，r＝－0.444 3，P＝0.026 1；图2B：右侧颞极e减低区e的AUC值与YGTSS总评分呈负相关关系，r＝－0.462 2，P＝0.020 0)

[1]	BattleDE. Diagnostic and statistical manual of mental disorders (DSM)[J]. Codas, 2013, 25(2): 191-192.
[2]	CavannaAE,SeriS. Tourette′s syndrome[J]. BMJ, 2013, 347: f4964.
[3]	GanosC,RoessnerV,MünchauA. The functional anatomy of Gilles de la Tourette syndrome[J]. Neurosci Biobehav Rev, 2013, 37(6): 1050-1062.
[4]	NeunerI,WernerCJ,ArrublaJ, et al. Imaging the where and when of tic generation and resting state networks in adult Tourette patients[J]. Front Hum Neurosci, 2014, 8(1): 362.
[5]	WangZ,MaiaTV,MarshR, et al. The neural circuits that generate tics in Tourette′s syndrome.[J]. Am J Psychiatry, 2011, 168(12): 1326-1337.
[6]	TinazS,BelluscioBA,MaloneP, et al. Role of the sensorimotor cortex in Tourette syndrome using multimodal imaging[J]. Hum Brain Mapp, 2014, 35(12): 5834-5846.
[7]	ChurchJA,FairDA,DosenbachNU, et al. Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity[J]. Brain, 2009, 132(1): 225-238.
[8]	ChurchJA,WengerKK,DosenbachNUF, et al. Task control signals in pediatric Tourette syndrome show evidence of immature and anomalous functional activity[J]. Front Hum Neurosci, 2009, 3(4): 38.
[9]	BassettDS,BullmoreET. Small-world brain networks revisited[J]. Neuroscientist, 2016, 23(5): 499-516.
[10]	TomasiD,VolkowND. Mapping small-world properties through development in the human brain: disruption in schizophrenia[J]. PLoS One, 2014, 9(4): e96176.
[11]	XiaS,FoxeJJ,SroubekAE, et al. Topological organization of the " small-world" visual attention network in children with attention deficit/hyperactivity disorder (ADHD)[J]. Front Hum Neurosci, 2014, 8(8): 162.
[12]	HeY,DagherA,ChenZ, et al. Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load[J]. Brain, 2009, 132(Pt 12): 3366-3379.
[13]	NelsonHE. A modified card sorting test sensitive to frontal lobe defects[J]. Cortex, 1976, 12(4): 313-324.
[14]	MacLeodCM. Half a century of research on the Stroop effect: an integrative review[J]. Psychol Bull, 1991, 109(2): 163-203.
[15]	LeckmanJF,RiddleMA,HardinMT, et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity[J]. J Am Acad Child Adolesc Psychiatry, 1989, 28(4): 566-573.
[16]	ZhangJ,WangJ,WuQ, et al. Disrupted brain connectivity networks in drug-naive, first-episode major depressive disorder[J]. Biol Psychiatry, 2011, 70(4): 334-342.
[17]	SuoX,LeiD,LiK, et al. Disrupted brain network topology in pediatric posttraumatic stress disorder: a resting-state fMRI study[J]. Hum Brain Mapp, 2015, 36(9): 3677-3686.
[18]	Tzourio-MazoyerN,LandeauB,PapathanassiouD, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain[J]. Neuroimage, 2002, 15(1): 273-289.
[19]	BenjaminiY,DraiD,ElmerG, et al. Controlling the false discovery rate in behavior genetics research[J]. Behav Brain Res, 2001, 125(1-2): 279-284.
[20]	SalvadorR,SucklingJ,ColemanMR, et al. Neurophysiological architecture of functional magnetic resonance images of human brain[J]. Cereb Cortex, 2005, 15(9): 1332-1342.
[21]	DecoG,TononiG,BolyM, et al. Rethinking segregation and integration: contributions of whole-brain modelling[J]. Nat Rev Neurosci, 2015, 16(7): 430-439.
[22]	PetersonBS,SkudlarskiP,AndersonAW, et al. A functional magnetic resonance imaging study of tic suppression in Tourette syndrome[J]. Arch Gen Psychiatry, 1998, 55(4): 326-333.
[23]	Hernández-LópezS,BargasJ,SurmeierDJ, et al. D1 receptor activation enhances evoked discharge in neostriatal medium spiny neurons by modulating an L-type Ca^2＋ conductance[J]. J Neurosci, 1997, 17(9): 3334-3342.
[24]	NicolaSM,SurmeierDJ,MalenkaRC. Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens[J]. Annu Rev Neurosci, 2000, 23(1): 185-215.
[25]	BerridgeKC,AldridgeJW. Super-stereotypy I: enhancement of a complex movement sequence by systemic dopamine D1 agonists[J]. Synapse, 2000, 37(3): 194-204.
[26]	MinkJW. The basal ganglia// Squire L, Berg D, Bloom FE, et al. Fundamental Neuroscience[M]. 4th Ed. Manhattan: Academic Press, 2014: 653-676.
[27]	GraybielAM. The basal ganglia and chunking of action repertoires[J]. Neurobiol Learn Mem, 1998, 70(1-2): 119-136.
[28]	OtmakhovaN,DuzelE,DeutchAY, et al. The hippocampal-VTA loop: the role of novelty and motivation in controlling the entry of information into long-term memory// Intrinsically motivated learning in natural and artificial systems[M]. Berlin: Springer, 2013: 235-254.
[29]	SchultzW,TremblayL,HollermanJR. Changes in behavior-related neuronal activity in the striatum during learning[J]. Trends Neurosci, 2003, 26(6): 321-328.
[30]	Vogt BA,FinchDM,OlsonCR. Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions[J]. Cereb Cortex, 1992, 2(6): 435-443.
[31]	HagmannP,CammounL,GigandetX, et al. Mapping the structural core of human cerebral cortex[J]. PLoS Biology, 2008, 6(7): e159.
[32]	LeechR,KamouriehS,BeckmannCF, et al. Fractionating the default mode network: distinct contributions of the ventral and dorsal posterior cingulate cortex to cognitive control[J]. J Neurosci, 2011, 31(9): 3217-3224.
[33]	HaydenBY,SmithDV,PlattML. Electrophysiological correlates of default-mode processing in macaque posterior cingulate cortex[J]. Proc Natl Acad Sci USA, 2009, 106(14): 5948-5953.

[1]	Xuan Zhang, Yutong Ma, Yuqian Miao, Yun Zhang, Shiwen Wu, Xiaochu Dang, Yingying Chen, Zhaoming Zhong, Xuejuan Wang, Miao Hu, Yanfeng Sun, Xiuzhu Ma, Faqin Lyu, Haiyan Kou. Ultrasound assessment of diaphragm function in pediatric patients with Duchenne muscular dystrophy[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(10): 1068-1073.
[2]	Baofu Zhang, Jin Yu, Jingjing Ye, Jiangen Yu, Xiaohui Ma, Xiwang Liu. Echocardioimagedata diagnosis of anomalous pulmonary venous connection caused by congenital malposition of the septum primum[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(10): 1074-1080.
[3]	Dan Han, Ting Wang, Huan Xiao, Lirong Zhu, Jingyu Chen, Yi Tang. Diagnostic value of contrast enhanced ultrasound versus contrast enhanced computed tomography in benign and malignant liver lesions in children[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(09): 939-944.
[4]	Tingting Liu, Yanbing Lin, Shan Wang, Murong Chen, Zijian Tang, Dongling Dai, Bei Xia. Evaluation of metabolic dysfunction-associated fatty liver disease in children by ultrasound-guided attenuation parameter[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(08): 787-794.
[5]	Yuhan Zhou, Huan Xiao, Chunjiang Yang, Juan Zhou, Lirong Zhu, Juan Xu, Fangting Mou. Diagnostic value of ultrasound in children with temporary hip synovitis[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(08): 795-800.
[6]	Jiu Wang, Jun Chen, Xia Zhu, Yangjin Mima, Sheng Zhao, Xinlin Chen, Jianhua Li, Shuang Wang. Effect of implementing fetal systemic ultrasound screening in Material and Child Health Hospital of Shannan[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(07): 728-733.
[7]	Jie Mi, Chen Chen, Jialing Li, Haina Pei, Hengbo Zhang, Fei Li, Dongjie Li. Analysis of the characteristics of children's head and face trauma[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2023, 18(06): 511-515.
[8]	Tao Ma, Chunwei Ye, Tao Liu, Wenxi Peng, Zhipeng Li. Comparison of laparoscopic and open disconnected pyeloplasty in the treatment of ureteropelvic junction obstruction in children[J]. Chinese Journal of Endourology(Electronic Edition), 2023, 17(06): 605-610.
[9]	Lei Wang, Shaohua Wang, Haizhen Niu, Tengfei Yin. Application of early warning intervention based on risk assessment in perioperative nursing of children with inguinal hernia[J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2023, 17(06): 768-772.
[10]	Fang Li, Rui Xu, Yangyang Li, Xiuquan Shi. Application of the concept of evidence-based medicine in children with inguinal hernia[J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2023, 17(06): 782-786.
[11]	Lei Lyu, Xiao Feng, Kaiming He, Kaining Zeng, Qing Yang, Haijin Lyu, Huimin Yi, Shuhong Yi, Yang Yang, Binsheng Fu. Value of revised King's score in evaluation of live transplantation timing for children with acute liver failure due to Wilson's disease and literature review[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(06): 661-668.
[12]	Xiangyu Zhu, Jianmei Wang, Hui Zhang, Hongying Ye. Correlation analysis between left ventricular function parameters and liver cirrhosis using non-invasive left ventricular pressure-strain cycle[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 494-498.
[13]	Shaohong Zhuo, Xiuling Lin, Cuimei Zhou, Weilian Xiong, Xingzao Ma. Application value of CD64 index combined with serum SAA/CRP and PCT in the diagnosis of children with infectious gastrointestinal diseases[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 505-509.
[14]	Zehui Huang, Jiexian Liang, Wei Zeng. Application of dexmedetomidine combined with esketamine in painless gastroscopy in children[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 510-513.
[15]	Jing Li, Lingling Zhang, Wei Xing. Value of concept of interest induction before anesthesia induction in pediatric surgery and its effect on family satisfaction[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(07): 812-817.

Viewed

Full text

Abstract

Please choose a citation manager

Content to export