Proj 2: Learning of executive fnct. (143-169)

这项研究的总体目标是通过经验性测试和进一步开发基于生物学的前额叶皮质和相关的皮质下系统(包括基底节和中脑多巴胺能核)的计算模型，了解不同大脑区域在执行功能学习中的具体作用。我们专注于两个具体的问题：(A)前额叶皮质区域抽象的、规则样的表征的学习，这通过使更好地概括到新的环境来支持灵活的行为；(B)反馈驱动的学习机制，根据我们的模型，它塑造了基底节对前额叶执行功能表征的自适应调制。这个计算模型框架的几个预测已经在不同的人群中成功测试，包括帕金森氏症患者和ADHD患者，这两个人都被认为涉及多巴胺能系统的障碍，因为它影响基底节和前额叶皮质。因此，这个模型对于理解执行功能的神经基础具有重要的意义，无论是在神经学上完好的人群还是在紊乱的人群中。 我们建议检验以下假设： 具体目标2.1：影响前额叶皮质表征学习的因素：首先，我们在年轻人和儿童身上测试了我们的计算模型中的一组预测。例如，分块训练应有助于发展抽象的、类似规则的表征，这反过来又支持对新任务背景的更好概括。其次，由于在我们的模型中，抽象学习的程度取决于主动维护的持续时间，所以可以根据抽象的相对程度和相应的维护持续时间来组织不同的PFC区域。我们在模型中探索了这一想法。 具体目标2.2：影响反馈学习的因素。我们通过使用多巴胺D2受体激动剂/拮抗剂，提供了一种更直接的测试，通过使用多巴胺D2受体激动剂/拮抗剂，可以更直接地测试事件相关电位信号对反馈信息(ERN)的反应，根据我们的模型，这应该对这些信号具有分离作用。我们还检验了情绪诱导是否能改变反馈反应的平衡，如事件相关电位的测量。最后，我们试图通过协调执行功能和负反馈学习研究来解开影响执行功能任务学习的多种因素。

The overarching goal of the proposed research is to understand the specific roles of different brain areas in the learning of executive function, by empirically testing and further developing a biologically-based computational model of the prefrontal cortex and associated subcortical systems (including the basal ganglia and midbrain dopaminergic nuclei). We focus on two specific issues: (a) the learning of abstract, rule-like representations in prefrontal cortical areas, which support flexible behavior by enabling better generalization to novel circumstances; and (b) the mechanisms of feedback-driven learning, which shape the adaptive modulation of prefrontal executive function representations by the basal ganglia, according to our model. Several predictions from this computational modeling framework have already been successfully tested in diverse populations, including Parkinson's patients and people with ADHD, both of which are thought to involve disorders of the dopaminergic system as it affects the basal ganglia and prefrontal cortex. Thus, this model has important implications for understanding the neural basis of executive function, both in neurologically intact and disordered populations. We propose to test the following hypotheses: ¿ Specific Aim 2.1: Factors Affecting Learning of Representations in Prefrontal Cortex: First, we test in both young adults and children a set of predictions from our computational model. For example, blocked training should facilitate the development of abstract, rule-like representations, which in turn support better generalization to novel task contexts. Second, because the degree of abstraction learning depends on the duration of active maintenance in our model, different regions of PFC may be organized according to relative degree of abstraction, and corresponding maintenance duration. We explore this idea in the model. ¿ Specific Aim 2.2: Factors Affecting Feedback Learning. We provide a more direct test of dopaminergic mediation of event-related potential signals responsive to feedback information (ERN) by administering dopamine D2 receptor agonists/antagonists, which should have dissociable effects on these signals according to our model. We also test whether mood induction can shift the balance of feedback responsiveness, as measured by ERP's. Finally, we attempt to disentangle multiple factors influencing learning of executive function tasks by using coordinated executive function and negative feedback learning studies in children.