Attention-deficit/hyperactivity disorder (ADHD) is associated with atypical fronto-subcortical neural circuitry and heightened delay discounting, or a stronger preference for smaller, immediate rewards over larger, delayed rewards. Recent evidence of ADHD-related sex differences in brain structure and function suggests anomalies in fronto-subcortical circuitry may differ among girls and boys with ADHD. The current study examined whether the functional connectivity (FC) within fronto-subcortical neural circuitry differs among girls and boys with ADHD compared to same-sex typically developing (TD) controls and relates to delay discounting. Participants include 8–12-year-old children with ADHD (n = 72, 20 girls) and TD controls (n = 75, 21 girls). Fronto-subcortical regions of interest were functionally defined by applying independent component analysis to resting-state fMRI data. Intrinsic FC between subcortical components, including the striatum and amygdala, and prefrontal components, including ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and anterior dorsolateral prefrontal cortex (dlPFC), was compared across diagnostic groups overall and within sex. Correlations between intrinsic FC of the six fronto-subcortical pairs and delay discounting were also examined. Both girls and boys with ADHD show atypical FC between vmPFC and subcortical regions including the striatum (stronger positive FC in ADHD) and amygdala (weaker negative FC in ADHD), with the greatest diagnostic effects among girls. In addition, girls with ADHD show atypical intrinsic FC between the striatum and dlPFC components, including stronger positive FC with ACC and stronger negative FC with dlPFC. Further, girls but not boys, with ADHD, show heightened real-time delay discounting. Brain–behavior correlations suggest (1) stronger negative FC between the striatal and dlPFC components correlated with greater money delay discounting across all participants and (2) stronger FC between the amygdala with both the dlPFC and ACC components was differentially related to heightened real-time discounting among girls and boys with and without ADHD. Our findings suggest fronto-subcortical functional networks are affected in children with ADHD, particularly girls, and relate to delay discounting. These results also provide preliminary evidence of greater disruptions in fronto-subcortical FC among girls with ADHD that is not due to elevated inattention symptom severity, intellectual reasoning ability, age, or head motion.

中文翻译：

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额叶皮层下固有功能连接中的ADHD相关性别差异及延迟贴现的关联

注意缺陷/多动障碍（ADHD）与非典型额叶皮层下神经回路和延迟折扣增加有关，或者与较大的，延迟的奖励相比，更倾向于较小的，立即的奖励。与多动症相关的大脑结构和功能的性别差异的最新证据表明，患有多动症的男孩和女孩的额下皮层回路异常可能有所不同。目前的研究检查了患有ADHD的男孩和女孩中额叶-皮层下神经回路内的功能连通性（FC）与同等发育的典型同性（TD）对照相比是否存在差异，并且与延迟贴现有关。参加者包括患有ADHD的8至12岁儿童（n = 72，20个女孩）和TD对照（n = 75，21，女孩）。通过将独立成分分析应用于静息状态fMRI数据在功能上定义了额额皮质下区域。在整个诊断组和性别诊断组之间比较了皮层下成分（包括纹状体和杏仁核）和前额叶成分（包括腹膜前额叶皮层（vmPFC），前扣带回皮层（ACC）和前背外侧前额叶皮层（dlPFC）之间的内在FC。还检查了六个额叶皮层下皮质对的固有FC与延迟贴现之间的相关性。ADHD的男孩和女孩在vmPFC和皮层下区域（包括纹状体（ADHD中较强的阳性FC）和杏仁核（ADHD中较弱的阴性FC））之间均表现出非典型FC，对女孩的诊断效果最大。此外，患有ADHD的女孩在纹状体和dlPFC成分之间显示非典型的内在FC，包括ACC较强的正FC和dlPFC较强的负FC。此外，患有多动症的女孩而非男孩表现出更高的实时延迟折扣。脑与行为的相关性提示：（1）纹状体和dlPFC成分之间的负FC增强，与所有参与者的延误折扣更大相关；（2）带有dlPFC和ACC成分的杏仁核之间的FC增强与实时性的提高存在差异有或没有多动症的女孩和男孩之间的折扣。我们的研究结果表明额叶皮层下功能网络在多动症儿童，特别是女孩中受到影响，并且与延迟贴现有关。