Chan Shi Yu, Chuah Jasmine Si Min, Huang Pei, Tan Ai Peng
Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A⁎STAR), 30 Medical Dr, Singapore 117609, Singapore.
Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A⁎STAR), 30 Medical Dr, Singapore 117609, Singapore; Yong Loo Lin School of Medicine, National University of Singapore (NUS), 10 Medical Dr, Singapore 117597, Singapore; Department of Diagnostic Imaging, National University Health System, 1E Kent Ridge Rd, Singapore 119228, Singapore.
Dev Cogn Neurosci. 2025 Jan;71:101483. doi: 10.1016/j.dcn.2024.101483. Epub 2024 Nov 25.
Autism spectrum disorder (ASD) is highly heterogeneous in presentation. While abnormalities in brain functional connectivity are consistently observed in autistic males, the neurobiological basis underlying the different domains of autism symptoms is unclear. In this study, we evaluated whether individual variations in functional connectivity deviations map to social behavior in ASD males. Using neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE), we modeled normative trajectories of between-network resting-state functional connectivity (rsFC) in non-ASD males across childhood (n = 321). These normative charts were then applied to ASD males (n = 418) to calculate individual deviation scores (z-scores) that reflect the degree of rsFC atypicality. Deviations in rsFC patterns among the default mode network (DMN), ventral attention network (VAN), frontoparietal network (FPN), and somatomotor network (SMN) were associated with distinct dimensions of social behavior. Cognitive flexibility and working memory mediated the association between VANxDMN z-scores and social behavioral problems. Our findings underscore the potential of normative models to identify atypical brain connectivity at an individual level, revealing the neurobiological patterns associated with social behavioral problems in ASD that are critical for precision diagnosis and intervention. Social outcomes in ASD males may be improved by targeting cognitive flexibility and working memory.
自闭症谱系障碍（ASD）在临床表现上具有高度异质性。虽然在自闭症男性中始终观察到大脑功能连接异常，但自闭症症状不同领域背后的神经生物学基础尚不清楚。在本研究中，我们评估了功能连接偏差的个体差异是否与ASD男性的社会行为相关。利用来自自闭症脑成像数据交换（ABIDE）的神经影像数据，我们建立了非ASD男性在童年期（n = 321）网络间静息态功能连接（rsFC）的规范轨迹模型。然后将这些规范图表应用于ASD男性（n = 418），以计算反映rsFC非典型程度的个体偏差分数（z分数）。默认模式网络（DMN）、腹侧注意网络（VAN）、额顶叶网络（FPN）和躯体运动网络（SMN）之间rsFC模式的偏差与社会行为的不同维度相关。认知灵活性和工作记忆介导了VANxDMN z分数与社会行为问题之间的关联。我们的研究结果强调了规范模型在个体水平上识别非典型脑连接的潜力，揭示了与ASD中社会行为问题相关的神经生物学模式，这对精确诊断和干预至关重要。针对认知灵活性和工作记忆可能会改善ASD男性的社会结局。
