孤独症谱系障碍男童脑岛与感觉及社交脑区功能连接特征

李小雪; 翟巾赫; 郝海莹; 徐子涵; 曹轩; 夏薇; 王佳

doi:10.16835/j.cnki.1000-9817.2023.03.004

孤独症谱系障碍男童脑岛与感觉及社交脑区功能连接特征

doi: 10.16835/j.cnki.1000-9817.2023.03.004

李小雪¹,
翟巾赫¹,
郝海莹¹,
徐子涵¹,
曹轩¹,
夏薇¹,
王佳^{1, 2, ,}

1.
哈尔滨医科大学公共卫生学院儿少卫生与妇幼保健学教研室，黑龙江 150081
2.
黑龙江省医学科学院

基金项目:

国家自然科学基金项目 81874210

黑龙江省自然科学基金 LH2022H051

详细信息

作者简介:
李小雪(1995-)，女，黑龙江省人，在读硕士，主要研究方向为儿童发育障碍和行为问题

通讯作者:
王佳，E-mail：wangjiahyd@163.com

利益冲突声明 所有作者声明无利益冲突。
中图分类号: R748 R338.2
计量
- 文章访问数: 387
- HTML全文浏览量: 174
- PDF下载量: 27
- 被引次数: 0
出版历程
- 收稿日期: 2022-08-20
- 修回日期: 2022-12-12
- 刊出日期: 2023-03-25

Functional connectivity among insula, sensory and social brain regions in boys with autism spectrum disorder

1.
Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin(150081), China

摘要

摘要: 目的探究孤独症谱系障碍(autism spectrum disorder, ASD)男童脑岛与感觉、社交相关脑区功能连接特征，为探索ASD男童感觉异常影响核心症状的中枢神经基础提供基础资料。方法收集在黑龙江省孤独症定点康复机构进行训练的34例ASD男童与29例幼儿园健康对照(TD组)男童的静息态功能磁共振数据，基于功能连接分析方法，以感觉相关脑区、脑岛、社交相关脑区为种子点，比较两组被试种子点间的功能连接(FC)水平的差异，结果经FDR校正。采用孤独症诊断观察量表(ADOS)、儿童孤独症评定量表(CARS)、孤独症特质量表-儿童版(AQ-Child)评估ASD男童的核心表型。结果与TD组相比，ASD组男童触觉、嗅觉和听觉脑区与脑岛之间的FC水平升高；脑岛与双侧杏仁核、内侧前额叶皮质(mPFC)之间的FC水平升高(P值均 < 0.05)。Pearson相关性分析表明，ASD组听觉脑区(BA42)与左侧脑岛FC值与ADOS的沟通(r=-0.44)、相互性社会互动(r=-0.43)、沟通和社会互动总分(r=-0.49)、AQ-Child的细节关注(r=-0.41)得分均呈负相关；右侧脑岛与右侧杏仁核FC值与AQ-Child的注意力转移得分均呈正相关(r=0.38)，右侧脑岛与mPFC间的FC值与ADOS的刻板行为和局限兴趣(r=0.48)、AQ-Child的注意力转移(r=0.49)、AQ-Child总分(r=0.41)、CARS总分(r=0.41)均呈正相关(P值均 < 0.05)。结论 ASD儿童脑岛与感觉、社交相关脑区功能连接存在异常，且与临床症状相关，可开展深入研究，探索其中枢神经机制。
- 孤独性障碍 /
- 脑 /
- 感觉 /
- 儿童 /
- 男(雄)性
Abstract: Objective To identify the functional connectivity characteristics of insula, sensory and social related brain regions in boys with autism spectrum disorder(ASD), to explore the central nervous basis of sensory abnormality affecting core symptoms in boys with ASD. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 34 boys with ASD and 29 typical development boys (TD group). Based on functional connectivity analysis, the sensory-related brain regions, insula, and social-related brain regions were taken as regions of interest to calculate the functional connectivity (FC) level between the regions of interest, the differences between the two groups were compared and the results were corrected by FDR. The Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS) and Autism Spectrum Quotient-Children's Version (AQ-Child) were used to assess the core phenotypes of boys with ASD. Results Compared with the TD group, the levels of FC between tactile brain regions and insula, olfactory brain regions and insula, auditory brain regions and insula in boys with ASD group were significantly increased. The level of FC between the insula and bilateral amygdala, insula and the medial prefrontal cortex(mPFC) were significantly increased(P < 0.05).Pearson correlation analysis showed that the level of FC between auditory brain region(BA42)and left insula in ASD group was negatively correlated with the scores of communication subscale of ADOS(r=-0.44), social interaction subscale of ADOS(r=-0.43), communication & social interaction subscale of ADOS(r=-0.49), attention to details subscale of AQ-Child(r=-0.41). The level of FC between the right insula and right amygdala was positively correlated with the attention switch subscale of AQ-Child(r=0.38), the level of FC between right insula and mPFC was positively correlated with the scores of repetitive behavior subscale of ADOS(r=0.48), the attention switch subscale of AQ-Child(r=0.49), total scale subscale of AQ-Child(r=0.41), total scale of CARS(r=0.41)(P < 0.05). Conclusion The levels of FC between insula and sensory-related, social-related brain regions are abnormal in children with ASD, which have significant correlations with clinical symptoms. In-depth studies can be conducted to explore underlying neutral mechanisms.
- Autistic disorder /
- Brain /
- Sensation /
- Child /
- Male
注释:

1) 利益冲突声明 所有作者声明无利益冲突。

HTML全文

表 1 用于功能连接分析的种子点

Table 1. Regions of interest for functional connectivity analysis

脑区	种子点	英文缩写
触觉脑区	ROI1	BA1
	ROI2	BA2
	ROI3	BA3
视觉脑区	ROI4	BA17
	ROI5	BA18
	ROI6	BA19
听觉脑区	ROI7	BA22
	ROI8	BA41
	ROI9	BA42
嗅觉脑区	ROI10	BA34
脑岛	ROI11	INS_L
	ROI12	INS_R
杏仁核	ROI13	AMY_L
内侧前额叶皮质	ROI14	AMY_R
	ROI15	mPFC
注：BA为布罗德曼分区；INS_L为左侧脑岛；INS_R为右侧脑岛；AMY_L为左侧杏仁核；AMY_R为右侧杏仁核；mPFC为内侧前额叶皮质。

下载: 导出CSV

表 2 ASD组与TD组儿童感觉、脑岛和社交脑区之间功能连接差异比较(x±s)

Table 2. Brain regions with different functional connections between sensory, insula and social brain regions in ASD and TD groups (x±s)

组别	人数	感觉-脑岛			脑岛-社交
组别	人数	BA2- INS_L	BA34-INS_R	BA42-INS_L	INS_R-AMY_L	INS_R-AMY_R	INS_R-mPFC
ASD组	34	2.37±2.33	5.33±2.54	4.20±2.54	4.45±2.62	6.71±2.65	0.86±2.40
TD组	29	0.42±2.93	2.76±2.76	1.99±2.93	1.59±3.10	4.62±2.39	-1.14±2.48
t值		2.95	3.85	3.20	3.97	3.27	3.25
P值		< 0.05	< 0.01	0.03	< 0.01	0.03	0.03
注：BA为布罗德曼分区；INS_L为左侧脑岛；INS_R为右侧脑岛；AMY_L为左侧杏仁核；AMY_R为右侧杏仁核；mPFC为内侧前额叶皮质。

下载: 导出CSV

表 3 ASD组男童FC值与孤独症临床评估结果相关系数(r值，n=34)

Table 3. Correlation analysis between FC values of boys with ASD group and autism behavior evaluation results(r, n=34)

量表	维度	BA42-INS_L	INS_R-AMY_R	INS_R-mPFC
ADOS	沟通	-0.44^*	-0.26	0.28
	社会互动	-0.43^*	0.05	0.29
	沟通和社会互动	-0.49^**	-0.10	0.32
	刻板行为和局限兴趣	-0.31	-0.16	0.48^**
AQ-Child	社会技能	0.12	0.05	0.21
	注意力转移	0.07	0.38^*	0.49^**
	细节关注	-0.41^*	-0.28	0.09
	沟通能力	-0.08	0.07	0.24
	想象能力	-0.18	0.01	0.34
	总分	-0.12	0.05	0.41^*
CARS	总分	-0.10	0.05	0.41^*
注：P < 0.05，*P < 0.01。BA为布罗德曼分区；INS_L为左侧脑岛；INS_R为右侧脑岛；AMY_R为右侧杏仁核；mPFC为内侧前额叶皮质。

下载: 导出CSV

参考文献(24)

[1]	American Psyciatric Association. Diagnostic and statistical manual of mental disorders: DSM-5[M]. Washington DC: American Psychiatric Association, 2013: 50-51.
[2]	MAENNER M J, SHAW K A, BAKIAN A V, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years-autism and developmental disabilities monitoring network, 11 sites, United States, 2018[J]. MMWR Surv Summ, 2021, 70(11): 1-16. doi: 10.15585/mmwr.ss7011a1
[3]	ZHOU H, XU X, YAN W, et al. Prevalence of autism spectrum disorder in China: a nationwide multi-center population-based study among children aged 6 to 12 years[J]. Neurosci Bull, 2020, 36(9): 961-971. doi: 10.1007/s12264-020-00530-6
[4]	GONG X, LI X, WANG Q, et al. Comparing visual preferences between autism spectrum disorder (ASD) and normal children to explore the characteristics of visual preference of ASD children by improved visual preference paradigm: a case-control study[J]. Transl Pediatr, 2021, 10(8): 2006-2015. doi: 10.21037/tp-21-294
[5]	MANSOUR Y, BURCHELL A, KULESZA R J. Central auditory and vestibular dysfunction are key features of autism spectrum disorder[J]. Front Integr Neurosci, 2021, 15: 743561. doi: 10.3389/fnint.2021.743561
[6]	BALASCO L, PROVENZANO G, BOZZI Y. Sensory abnormalities in autism spectrum disorders: a focus on the tactile domain, from genetic mouse models to the clinic[J]. Front Psychiatry, 2020, 10: 1016. doi: 10.3389/fpsyt.2019.01016
[7]	SCHAFFLER M, MIDDLETON L, ABDUS-SABOOR I. Mechanisms of tactile sensory phenotypes in autism: current understanding and future directions for research[J]. Curr Psychiatry Rep, 2019, 21(12): 134. doi: 10.1007/s11920-019-1122-0
[8]	GOGOLLA N. The insular cortex[J]. Curr Biol, 2017, 27(12): R580-R586. doi: 10.1016/j.cub.2017.05.010
[9]	汤宜朗, 郭延庆, CATHERINE E R, 等. 孤独症诊断的金标准之一《孤独症诊断观察量表》介绍[J]. 国际精神病学杂志, 2010, 37(1): 38-40. https://www.cnki.com.cn/Article/CJFDTOTAL-GWYJ201001011.htm TANG Y L, GUO Y Q, CATHERINE E R, et al. Introduction of Autism Diagnostic Observation Scale one of the gold standards of autism diagnosis[J]. Int J Psychiatry, 2010, 37(1): 38-40. https://www.cnki.com.cn/Article/CJFDTOTAL-GWYJ201001011.htm
[10]	卢建平, 杨志伟, 舒明耀, 等. 儿童孤独症量表评定的信度、效度分析[J]. 中国现代医学杂志, 2004, 14(13): 119-121, 123. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXDY200413037.htm LU J P, YANG Z W, SHU M Y, et al. Raliability, validity analysis of the Childhood Autism Rating Scale[J]. Chin J Mod Med, 2004, 14(13): 119-121, 123. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXDY200413037.htm
[11]	李洪成, 李雪, 刘靖, 等. 孤独症谱系儿童版-中文简化版的信效度研究[J]. 中国全科医学, 2019, 22(21): 2606-2610. doi: 10.12114/j.issn.1007-9572.2019.00.085 LI H C, LI X, LIU J, et al. Reliability and validity of the Chinese Version of the Short Abridged Autism Spectrum Quotient-Children's Version[J]. Chin Gen Pract, 2019, 22(21): 2606-2610. doi: 10.12114/j.issn.1007-9572.2019.00.085
[12]	郭璇, 朱远来, 焦小燕, 等. 汉语版、哈萨克语版皮博迪图片词汇测验第四版的效度与信度[J]. 中国心理卫生杂志, 2019, 33(11): 845-850. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXWS201911010.htm GUO X, ZHU Y L, JIAO X Y, et al. Validity and reliability of the Chinese and Kazakh Versions of the Peabody Picture Vocabulary Test: forth edition in preschool children[J]. Chin J Ment Health, 2019, 33(11): 845-850. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXWS201911010.htm
[13]	BRODMANN K. Brodmann's localisation in the cerebral cortex[M]. Boston, MA: Springer, 2006.
[14]	MVLLER R A, FISHMAN I. Brain connectivity and neuroimaging of social networks in autism[J]. Trends Cogn Sci, 2018, 22(12): 1103-1116. doi: 10.1016/j.tics.2018.09.008
[15]	SCHLAGENHAUF F, STERZER P, SCHMACK K, et al. Reward feedback alterations in unmedicated schizophrenia patients: relevance for delusions[J]. Biol Psychiatry, 2009, 65(12): 1032-1039. doi: 10.1016/j.biopsych.2008.12.016
[16]	AVERY J A, INGEHOLM J E, WOHLTJEN S, et al. Neural correlates of taste reactivity in autism spectrum disorder[J]. Neuroimag Clin, 2018, 19: 38-46. doi: 10.1016/j.nicl.2018.04.008
[17]	GREEN S A, HERNANDEZ L, BOOKHEIMER S Y, et al. Salience network connectivity in autism is related to brain and behavioral markers of sensory overresponsivity[J]. J Am Acad Child Adolesc Psychiatry, 2016, 55(7): 618-626. doi: 10.1016/j.jaac.2016.04.013
[18]	WILSON K C, KORNISCH M, IKUTA T. Disrupted functional connectivity of the primary auditory cortex in autism[J]. Psychiatry Res Neuroimag, 2022, 324: 111490. doi: 10.1016/j.pscychresns.2022.111490
[19]	JAO K R J, PUESCHEL E B, GAO Y, et al. Underconnectivity between visual and salience networks and links with sensory abnormalities in autism spectrum disorders[J]. J Am Acad Child Adolesc Psychiatry, 2021, 60(2): 274-285. doi: 10.1016/j.jaac.2020.02.007
[20]	ABBOTT A E, NAIR A, KEOWN C L, et al. Patterns of atypical functional connectivity and behavioral links in autism differ between default, salience, and executive networks[J]. Cereb Cortex, 2016, 26(10): 4034-4045. doi: 10.1093/cercor/bhv191
[21]	LI L, HE C, JIAN T, et al. Attenuated link between the medial prefrontal cortex and the amygdala in children with autism spectrum disorder: evidence from effective connectivity within the "social brain"[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2021, 111: 110147. doi: 10.1016/j.pnpbp.2020.110147
[22]	CHEN Y Y, ULJAREVIC M, NEAL J, et al. Excessive functional coupling with less variability between salience and default mode networks in autism spectrum disorder[J]. Biol Psychiatry Cogn Neurosci Neuroimag, 2022, 7(9): 876-884.
[23]	VON DEM HAGEN E A, STOYANOVA R S, BARON-COHEN S, et al. Reduced functional connectivity within and between "social" resting state networks in autism spectrum conditions[J]. Soc Cogn Affect Neurosci, 2013, 8(6): 694-701. doi: 10.1093/scan/nss053
[24]	GUO X, DUAN X, SUCKLING J, et al. Partially impaired functional connectivity states between right anterior insula and default mode network in autism spectrum disorder[J]. Hum Brain Mapp, 2019, 40(4): 1264-1275.