儿童抽动秽语综合征小世界网络研究

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

中华妇幼临床医学杂志(电子版) ›› 2018, Vol. 14 ›› Issue (02) : 133 -140. doi: 10.3877/cma.j.issn.1673-5250.2018.02.002

所属专题：文献；

论著

儿童抽动秽语综合征小世界网络研究

廖怡¹, 曲海波¹^,^†(

), 蔡晓唐², 宁刚¹, 蒋月薪¹, 鲍莉¹, 张毓瑾¹, 李学胜¹, 孙怀强³

^1. 610041　成都，四川大学华西第二医院放射科、出生缺陷与相关妇儿疾病教育部重点实验室
^2. 610041　成都，四川大学华西第二医院儿童神经科
^3. 610041　成都，四川大学华西医院放射科华西磁共振研究中心

收稿日期:2017-11-19 修回日期:2018-02-28 出版日期:2018-04-01
通信作者: 曲海波

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

Yi Liao¹, Haibo Qu¹^,^†(), Xiaotang Cai², Gang Ning¹, Yuexin Jiang¹, Li Bao¹, Yujin Zhang¹, Xuesheng Li¹, Huaiqiang Sun³

^1. Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, Sichuan Province, China
^2. Department of Pediatrical Neurology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
^3. Huaxi MR Research Center, Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China

Received:2017-11-19 Revised:2018-02-28 Published:2018-04-01
Corresponding author: Haibo Qu
About author:
Corresponding author: Qu Haibo, Email: windowsqhb@126.com

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引用本文：

廖怡, 曲海波, 蔡晓唐, 宁刚, 蒋月薪, 鲍莉, 张毓瑾, 李学胜, 孙怀强. 儿童抽动秽语综合征小世界网络研究[J]. 中华妇幼临床医学杂志(电子版), 2018, 14(02): 133-140.

Yi Liao, Haibo Qu, Xiaotang Cai, Gang Ning, Yuexin Jiang, Li Bao, Yujin Zhang, Xuesheng Li, Huaiqiang Sun. Research of brain small-world network in children with Tourette syndrome[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2018, 14(02): 133-140.

目的

应用静息态功能MRI(rs-fMRI)，对儿童抽动秽语综合征(TS)患儿脑小世界网络特征，以及TS的网络区域属性与临床症状的相关性进行研究。

方法

选择2015年9月至2017年8月，于四川大学华西第二医院就诊，并且被诊断为儿童TS的25例患儿为研究对象，纳入研究组。选择同期于本院进行体检的22例健康儿童，纳入对照组。采集2组受试儿的rs-fMRI相关数据，采用GRETNA软件进行分析，得到全脑网络属性与区域网络属性有差异的脑区，并且对其临床资料进行相关性分析。采用χ²检验，对2组受试儿的性别构成比进行比较。采用独立样本t检验，对2组受试儿的年龄进行比较。采用Wilcoxon秩和检验，对2组受试儿的受教育年限进行比较。采用非参数置换检验，对2组受试儿的全脑及局部网络属性参数进行比较。采用直线相关性分析，对节点效率(e)减低脑区的曲线下面积(AUC)与《耶鲁综合抽动症状量表(YGTSS)》总评分进行相关性分析。本研究遵循的程序符合四川大学华西第二医院人体试验委员会所制定的伦理学标准，得到该委员会批准，分组征得受试儿监护人的知情同意，并与之签署临床研究知情同意书。

结果

①研究组与对照组受试儿的性别构成比、年龄、受教育年限等一般临床资料比较，差异均无统计学意义(P>0.05)。②研究组受试儿的YGTSS评分结果：躯体抽动总评分为(13.32±2.94)分，发声抽动总评分为(4.84±5.10)分，YGTSS总评分为(42.16±12.59)分。③研究组和对照组受试儿全脑网络均表现出小世界网络属性。与对照组相比，研究组受试儿的全脑效率(Eglob)显著降低，2组比较，差异有统计学意义(P＝0.014 1)；而特征路径长度(Lp)、标准化特征路径长度(λ)则均显著增加，差异均有统计学意义(P＝0.008 2、0.035 7)。与对照组相比，研究组左侧后扣带回(PCC)的e显著降低，2组比较，差异有统计学意义(P<0.000 1)；而右侧壳核e亦显著减低，差异有统计学意义(P＝0.000 3)，这2组数据均采取错误发现率(FDR)校正。④研究组受试儿左侧岛盖部额下回及右侧颞极e减低区的AUC值与YGTSS总评分，均呈负相关关系(r＝－0.444 3，P＝0.026 1；r＝－0.462 2，P＝0.020 0)。

结论

本研究揭示了儿童TS全脑网络具有小世界网络属性。TS患儿神经网络全脑及其诸个节点属性与正常儿童比较存在差异，其Eglob减低，而Lp、λ增加，趋向于向规则网络转换。儿童TS患儿的神经网络全脑诸个节点属性异常脑区，聚集于大脑皮质-纹状体-丘脑-大脑皮质(CSTC)环路，这揭示其脑网络特点，对评估儿童TS的疾病状态及对该病的治疗，提供了全脑网络生物学标志物。

关键词: 抽动秽语综合征, 静息态功能磁共振成像, 小世界网络, 儿童

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)

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

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