Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography
Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography
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DOI：
10.1038/npp.2015.18
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发表时间：
2015-06-01
影响因子：
7.6
通讯作者：
Posner, Jonathan
中科院分区：
文献类型：
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作者：
Cha, Jiook;Fekete, Tomer;Posner, Jonathan
攻击性在患有注意力缺陷/多动障碍（ADHD）的儿童中被广泛观察到，并且经常与挫折或对奖励的不满意的预期有关。尽管动物研究和人类功能性神经成像暗示了攻击行为中奖赏处理的改变，但之前没有研究证明前额-伏隔回路（通往皮层下边缘区域的关键皮质通路）与未接受药物治疗的多动症儿童的攻击行为之间的关系。为了解决这个问题，我们收集了30名ADHD儿童和31名健康对照（平均年龄，10 +/- 2.1 SD）的行为测量和攻击和冲动的父母报告，以及结构和扩散MRI。利用灰质形态测量和概率神经束造影结合多元统计模型（偏最小二乘回归和支持向量回归），我们确定了儿童多动症患者额伏神经回路中的异常，这些异常与攻击性增加有关。更具体地说，与HC相比，ADHD儿童表现出右侧伏核体积和额-伏核白质连通性的减少。ADHD组中伏核体积减小的幅度与攻击性增加显著相关，这种效应是由伏核体积和冲动性之间的关系介导的。此外，攻击性，而非冲动性，可以通过额-伏隔白质连通性和眶额皮质皮质厚度的多变量测量得到显著解释。我们的多模态成像结合多元统计模型表明，额伏神经回路是ADHD儿童攻击行为的重要基础。这些发现表明，旨在探测额伏神经回路的策略可能有助于治疗儿童多动症的攻击行为。
Aggression is widely observed in children with attention deficit/hyperactivity disorder (ADHD) and has been frequently linked to frustration or the unsatisfied anticipation of reward. Although animal studies and human functional neuroimaging implicate altered reward processing in aggressive behaviors, no previous studies have documented the relationship between fronto-accumbal circuitry-a critical cortical pathway to subcortical limbic regions-and aggression in medication-naive children with ADHD. To address this, we collected behavioral measures and parental reports of aggression and impulsivity, as well as structural and diffusion MRI, from 30 children with ADHD and 31 healthy controls (HC) (mean age, 10 +/- 2.1 SD). Using grey matter morphometry and probabilistic tractography combined with multivariate statistical modeling (partial least squares regression and support vector regression), we identified anomalies within the fronto-accumbal circuit in childhood ADHD, which were associated with increased aggression. More specifically, children with ADHD showed reduced right accumbal volumes and frontal-accumbal white matter connectivity compared with HC. The magnitude of the accumbal volume reductions within the ADHD group was significantly correlated with increased aggression, an effect mediated by the relationship between the accumbal volume and impulsivity. Furthermore, aggression, but not impulsivity, was significantly explained by multivariate measures of fronto-accumbal white matter connectivity and cortical thickness within the orbitofrontal cortex. Our multi-modal imaging, combined with multivariate statistical modeling, indicates that the fronto-accumbal circuit is an important substrate of aggression in children with ADHD. These findings suggest that strategies aimed at probing the fronto-accumbal circuit may be beneficial for the treatment of aggressive behaviors in childhood ADHD.