Park Shinwon, Haak Koen V, Cho Han Byul, Valk Sofie L, Bethlehem Richard A I, Milham Michael P, Bernhardt Boris C, Di Martino Adriana, Hong Seok-Jun
Institute for Basic Science, Center for Neuroscience Imaging Research, Sungkyunkwan University, Suwon, South Korea.
Department of Biomedical Engineering, Sungkyunkwan University, Suwon, South Korea.
Front Psychiatry. 2021 Aug 20;12:699813. doi: 10.3389/fpsyt.2021.699813. eCollection 2021.
A notable characteristic of autism spectrum disorder (ASD) is co-occurring deficits in low-level sensory processing and high-order social interaction. While there is evidence indicating detrimental cascading effects of sensory anomalies on the high-order cognitive functions in ASD, the exact pathological mechanism underlying their atypical functional interaction across the cortical hierarchy has not been systematically investigated. To address this gap, here we assessed the functional organisation of sensory and motor areas in ASD, and their relationship with subcortical and high-order trandmodal systems. In a resting-state fMRI data of 107 ASD and 113 neurotypical individuals, we applied advanced connectopic mapping to probe functional organization of primary sensory/motor areas, together with targeted seed-based intrinsic functional connectivity (iFC) analyses. In ASD, the connectopic mapping revealed topological anomalies (i.e., excessively more segregated iFC) in the motor and visual areas, the former of which patterns showed association with the symptom severity of restricted and repetitive behaviors. Moreover, the seed-based analysis found diverging patterns of ASD-related connectopathies: decreased iFCs within the sensory/motor areas but increased iFCs between sensory and subcortical structures. While decreased iFCs were also found within the higher-order functional systems, the overall proportion of this anomaly tends to increase along the level of cortical hierarchy, suggesting more dysconnectivity in the higher-order functional networks. Finally, we demonstrated that the association between low-level sensory/motor iFCs and clinical symptoms in ASD was mediated by the high-order transmodal systems, suggesting pathogenic functional interactions along the cortical hierarchy. Findings were largely replicated in the independent dataset. These results highlight that atypical integration of sensory-to-high-order systems contributes to the complex ASD symptomatology.
自闭症谱系障碍（ASD）的一个显著特征是在低水平感觉处理和高阶社会互动方面同时存在缺陷。虽然有证据表明感觉异常对ASD中的高阶认知功能有有害的级联效应，但它们在整个皮质层级中跨区域的非典型功能相互作用背后的确切病理机制尚未得到系统研究。为了填补这一空白，我们评估了ASD中感觉和运动区域的功能组织，以及它们与皮质下和高阶跨模态系统的关系。在107名ASD患者和113名神经典型个体的静息态功能磁共振成像（fMRI）数据中，我们应用先进的连接拓扑映射来探究初级感觉/运动区域的功能组织，并进行了基于目标种子的内在功能连接（iFC）分析。在ASD患者中，连接拓扑映射揭示了运动和视觉区域的拓扑异常（即过度分离的iFC），其中前者的模式与受限和重复行为的症状严重程度相关。此外，基于种子的分析发现了与ASD相关的连接病变的不同模式：感觉/运动区域内的iFC减少，但感觉和皮质下结构之间的iFC增加。虽然在高阶功能系统中也发现了iFC减少的情况，但这种异常的总体比例倾向于随着皮质层级的升高而增加，这表明高阶功能网络中存在更多的功能连接障碍。最后，我们证明了ASD中低水平感觉/运动iFC与临床症状之间的关联是由高阶跨模态系统介导的，这表明在整个皮质层级中存在致病的功能相互作用。这些发现在独立数据集中得到了很大程度的重复。这些结果突出表明，从感觉系统到高阶系统的非典型整合导致了复杂的ASD症状。
