Objective:

A large body of functional MRI research has examined a potential role for subcortico-cortical loops in the pathogenesis of attention deficit hyperactivity disorder (ADHD), but has produced inconsistent findings. The authors performed a mega-analysis of six neuroimaging data sets to examine associations between ADHD diagnosis and traits and subcortico-cortical connectivity.

Methods:

Group differences were examined in the functional connectivity of four subcortical seeds in 1,696 youths with ADHD diagnoses (66.39% males; mean age, 10.83 years [SD=2.17]) and 6,737 unaffected control subjects (47.05% males; mean age, 10.33 years [SD=1.30]). The authors examined associations between functional connectivity and ADHD traits (total N=9,890; 50.3% males; mean age, 10.77 years [SD=1.96]). Sensitivity analyses were used to examine specificity relative to commonly comorbid internalizing and non-ADHD externalizing problems. The authors further examined results within motion-matched subsamples, and after adjusting for estimated intelligence.

Results:

In the group comparison, youths with ADHD showed greater connectivity between striatal seeds and temporal, fronto-insular, and supplementary motor regions, as well as between the amygdala and dorsal anterior cingulate cortex, compared with control subjects. Similar findings emerged when ADHD traits were considered and when alternative seed definitions were adopted. Dominant associations centered on the connectivity of the caudate bilaterally. Findings were not driven by in-scanner motion and were not shared with commonly comorbid internalizing and externalizing problems. Effect sizes were small (largest peak d, 0.15).

Conclusions:

The findings from this large-scale mega-analysis support established links with subcortico-cortical circuits, which were robust to potential confounders. However, effect sizes were small, and it seems likely that resting-state subcortico-cortical connectivity can capture only a fraction of the complex pathophysiology of ADHD.

中文翻译：

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ADHD 中的皮质下皮质不连接：跨多个队列的体素大型分析

客观的：

大量的功能性 MRI 研究已经检验了皮质下-皮质环路在注意力缺陷多动障碍 (ADHD) 发病机制中的潜在作用，但得出的结果不一致。作者对六个神经影像数据集进行了大规模分析，以检查多动症诊断与特征和皮质下皮质连接之间的关联。

方法：

对 1,696 名患有 ADHD 诊断的青少年（66.39% 男性；平均年龄，10.83 岁 [SD=2.17]）和 6,737 名未受影响的对照受试者（47.05% 男性；平均年龄，10.33 岁 [SD=2.17]）的四个皮层下种子的功能连接进行了组间差异检查。标准差=1.30]）。作者检查了功能连接与 ADHD 特征之间的关联（总 N=9,890；50.3% 男性；平均年龄，10.77 岁 [SD=1.96]）。敏感性分析用于检查与常见共病内化和非 ADHD 外化问题相关的特异性。作者进一步检查了运动匹配子样本中的结果，并在调整了估计智力后。

结果：

在组比较中，与对照组相比，患有多动症的青少年在纹状体种子和颞叶、额岛和辅助运动区域之间以及杏仁核和背侧前扣带皮层之间表现出更大的连通性。当考虑多动症特征并采用替代种子定义时，出现了类似的发现。主导关联集中于双边尾状核的连接。研究结果不是由扫描仪内运动驱动的，也不是常见共病的内化和外化问题。效应量很小（最大峰 d，0.15）。

结论：

这项大规模大型分析的结果支持与皮质下皮质回路建立联系，这对于潜在的混杂因素来说是稳健的。然而，效应大小很小，而且静息态皮质下皮质连接似乎只能捕获 ADHD 复杂病理生理学的一小部分。