Chuah Jasmine Si Min, Manahan Aisleen M A, Chan Shi Yu, Ngoh Zhen Ming, Huang Pei, Tan Ai Peng
Agency for Science, Technology and Research, Institute for Human Development and Potential (IHDP), Singapore, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore.
Autism Res. 2025 Jan;18(1):70-82. doi: 10.1002/aur.3280. Epub 2024 Dec 5.
The thalamus has extensive cortical connections and is an integrative hub for cognitive functions governing social behavior. This study examined (1) associations between thalamocortical resting-state functional connectivity (RSFC) and social behavior in children and (2) how various executive function (EF) subdomains mediate the association between thalamocortical RSFC and social behavior. Children from the autism brain imaging data exchange (ABIDE) initiative with neuroimaging, behavioral, and demographic data were included in our study (age < 14, ASD; n = 207, typically developing; n = 259). Thalamocortical RSFC was examined for associations with social communication and interaction (SCI) scores (SRS; social responsiveness scale) using Spearman's rank-order correlation, first in ASD children and then in typically developing children. This was followed by a more granular analysis at the thalamic subregion level. We then examined the mediating roles of eight EF subdomains in ASD children (n = 139). Right thalamus-default mode network (DMN) RSFC was significantly associated with SCI scores in ASD children (ρ = 0.23, p = 0.012), primarily driven by the medial (ρ = 0.22, p = 0.013), ventral (ρ = 0.17, p = 0.036), and intralaminar (ρ = 0.17, p = 0.036) thalamic subregions. Cognitive flexibility (ACME = 0.13, p = 0.016) and emotional control (ACME = 0.08, p = 0.020) significantly mediated the association between right thalamus-DMN RSFC and SCI scores. This study provided novel insights into the association between thalamocortical RSFC and social behavior in ASD children at the thalamic subregion level, providing higher levels of precision in brain-behavior mapping. Cognitive flexibility and emotion regulation were highlighted as potential targets to ameliorate the downstream effects of altered thalamocortical connectivity to improve social outcomes in ASD children.
丘脑具有广泛的皮质连接，是支配社会行为的认知功能的整合枢纽。本研究考察了（1）儿童丘脑皮质静息态功能连接（RSFC）与社会行为之间的关联，以及（2）各种执行功能（EF）子领域如何介导丘脑皮质RSFC与社会行为之间的关联。来自自闭症脑成像数据交换（ABIDE）计划且拥有神经影像学、行为学和人口统计学数据的儿童被纳入我们的研究（年龄<14岁，自闭症谱系障碍；n = 207，发育正常；n = 259）。首先在自闭症谱系障碍儿童中，然后在发育正常的儿童中，使用斯皮尔曼等级相关法检验丘脑皮质RSFC与社会沟通和互动（SCI）分数（社交反应量表）之间的关联。随后在丘脑亚区域水平进行了更细致的分析。然后我们考察了八个EF子领域在自闭症谱系障碍儿童（n = 139）中的中介作用。右侧丘脑-默认模式网络（DMN）RSFC与自闭症谱系障碍儿童的SCI分数显著相关（ρ = 0.23，p = 0.012），主要由丘脑内侧（ρ = 0.22，p = 0.013）、腹侧（ρ = 0.17，p = 0.036）和板内核（ρ = 0.17，p = 0.036）亚区域驱动。认知灵活性（ACME = 0.13，p = 0.016）和情绪控制（ACME = 0.08，p = 0.020）显著介导了右侧丘脑-DMN RSFC与SCI分数之间的关联。本研究在丘脑亚区域水平上为自闭症谱系障碍儿童丘脑皮质RSFC与社会行为之间的关联提供了新的见解，在脑-行为映射方面提供了更高的精确性。认知灵活性和情绪调节被强调为改善丘脑皮质连接改变的下游效应以改善自闭症谱系障碍儿童社会结局的潜在靶点。
