A brain imaging study on conditioning deficits in antisocial youths

 描述(申请人提供)：破坏性行为障碍(DBD)，包括品行障碍和对立违抗障碍，是儿童最常见和最重要的临床障碍之一。从理论上讲，神经生物标志物可以带来客观信息 到诊断过程中。当个体考虑从事反社会行为时，未能在线索和负面后果之间建立联系可能会导致缺乏焦虑和预期恐惧，从而导致更多的反社会行为。同样，不能区分预测奖励的线索和非预测性线索，可能会导致适当行为的刺激强化学习受到影响。目前尚不清楚为什么一些儿童会患上DBD，为什么他们不像典型的发育中的儿童那样，学会用适当的行为来取代不适当的行为。这项研究的长期目标是确定与DBD相关的情绪学习缺陷的神经机制。中心假设是大脑回路中的非典型激活，包括杏仁核、纹状体和腹内侧额前皮质(VmPFC)，将与年轻人在食欲和厌恶条件反射的背景下的破坏性行为有关。假说将通过追求三个具体目标来检验：1)确定青少年对次级补充剂的嗜好和厌恶条件作用的神经基础；2)确定DBD高危青少年大脑功能异常；3)确定高危青少年冷酷无情(CU)个性特征、精神变态向下延伸和破坏性行为的独特神经生物学协变量。这项研究计划从68名(34名高风险和34名低风险)11至12岁的社区样本中获取脑成像数据，当时他们正在接受以金钱收益和金钱损失为强化因素的经典条件反射范式。初步结果表明，我们的条件反射范式在诱发皮肤电条件化反应方面是有效的，并将破坏性行为与皮肤电条件化缺陷与货币增强剂联系起来。这项研究方案具有创新性，因为：(1)它首次使用功能磁共振成像来确定患有DBD风险儿童的食欲和厌恶条件缺陷的神经基础，(2)它使用具有社会意义的增强剂(金钱损失或获得)来研究条件作用的神经基础，以及(3)它确定了高危青少年破坏性行为和CU个性特征的独特神经生物学协变量。NIH支持这一提议将为申请者提供过渡到独立调查人员所需的经验。确定与DBDS相关的条件性缺陷的神经机制有可能揭示与DBDS的发展有关的潜在的精神病理过程。这一知识对临床诊断和行为矫正治疗计划具有潜在的意义，并可能有助于针对那些最有需要的儿童进行有针对性的治疗。

 DESCRIPTION (provided by applicant): Disruptive behavior disorders (DBDs), which include conduct disorder and oppositional defiant disorder, are among the most common and important clinical disorders in children. Neurobiological markers could in theory bring objective information to the diagnostic process. Failure to form associations between cues and negative consequences may result in lack of anxiety and anticipatory fear whenever the individual contemplates the engagement in an antisocial act, thus leading to more antisocial behavior. Similarly, inability to differentiate cues that predict rewards and non-predictive cues may result in compromised stimulus- reinforcement learning of appropriate behaviors. It is unknown why some children develop DBDs and why they do not learn to substitute inappropriate behaviors with appropriate behaviors, as typically-developing children do. The long term goal of this study is to identify neural mechanisms that contribute to the emotional learning deficits associated with DBDs. The central hypotheses are atypical activation in brain circuitries, including amygdala, striatum, and ventromedial prefrontal cortex (vmPFC), will be associated with disruptive behaviors in youths in the context of appetitive and aversive conditioning. Hypotheses will be tested by pursuing three specific aims: 1) to determine the neural substrates underlying appetitive and aversive conditioning to secondary reinforcers in youths; 2) to determine the functional abnormality in the brains of youths at risk for DBDs, and 3) to determine the unique neurobiological covariates of callous-unemotional (CU) personality traits, the downward extension of psychopathy, and disruptive behaviors in high-risk youths. This study plans to acquire brain imaging data from a community sample of 68 (34 high- and 34 low- risk) 11- to 12-year-olds when they are undergoing a classical conditioning paradigm with monetary gain and monetary loss as reinforcers. Preliminary results have indicated that our conditioning paradigm is valid in eliciting electrodermal conditioning responses, and have linked disruptive behaviors with electrodermal conditioning deficits to monetary reinforcers. The research proposal is innovative because: (1) for the first time it uses fMRI to determine the neural substrates underlying appetitive and aversive conditioning deficits in children at risk for DBDs, (2) it investigates the neural bases of conditioning using socially meaningful reinforcers (monetary loss or gain), and (3) it determines the unique neurobiological covariates of disruptive behaviors and CU personality traits in high-risk youths. NIH support of this proposal will provide the applicant with the experience necessary to transition into an independent investigator. Determination of the neural mechanisms that contribute to the conditioning deficits related to DBDs has the potential to uncover underlying psychopathological processes involved in the development of DBDs. This knowledge has potential implications for clinical diagnosis and behavioral modification treatment programs, and may help to target treatment efforts on those children in most need.