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

项目 2：学习执行功能。

• 批准号: 8378643
• 负责人: RANDALL CHARLES O'REILLY
• 金额: $ 14.29万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8378643
• 关键词: Address; Adolescence; Affect; Agonist; Anterior; Area; Attention deficit hyperactivity disorder; Basal Ganglia; Behavior; Biological; Brain; Cell Nucleus; Child; Complex; Computer Simulation; Development; Diamond; Disease; Disputes; Dopamine; Dopamine D2 Receptor; Dopaminergic Agents; Dorsal; Equilibrium; Event-Related Potentials; Feedback; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Human; Individual Differences; Inferior; Lateral; Learning; Link; Maintenance; Measures; Mediating; Mediation; Midbrain structure; Modeling; Moods; Nature; Neurobiology; Neurons; Parkinson Disease; Patients; Population; Population Heterogeneity; Prefrontal Cortex; Process; Property; Relative (related person); Research; Rewards; Role; Shapes; Short-Term Memory; Signal Transduction; System; Testing; Time; Training; Update; Vocabulary; abstracting; base; executive function; flexibility; improved; neural patterning; novel; psychologic; relating to nervous system; research study; response; young adult

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.

拟议研究的总体目标是了解不同大脑区域在执行功能学习中的具体作用，通过经验测试和进一步开发前额叶皮层和相关皮层下系统（包括基底神经节和中脑多巴胺能核）的基于生物学的计算模型。我们专注于两个具体问题：（a）学习抽象的，规则般的表征在前额叶皮层区域，支持灵活的行为，使更好地概括到新的情况下;（B）反馈驱动的学习机制，形成自适应调制的前额叶执行功能的表征，根据我们的模型。这个计算模型框架的几个预测已经在不同的人群中成功地进行了测试，包括帕金森病患者和多动症患者，这两种患者都被认为涉及多巴胺能系统的疾病，因为它影响基底神经节和前额叶皮层。因此，该模型对于理解执行功能的神经基础具有重要意义，无论是在神经系统完整的人群还是在神经系统紊乱的人群中。 我们建议检验以下假设： 具体目标2.1：影响前额叶皮层表征学习的因素：首先，我们在年轻人和儿童中测试了一组来自我们计算模型的预测。例如，分块训练应该促进抽象的、规则般的表征的发展，这反过来又支持更好地概括新的任务上下文。第二，由于抽象学习的程度取决于主动维护的持续时间，在我们的模型中，PFC的不同区域可以根据相对抽象程度和相应的维护持续时间来组织。我们在模型中探索这个想法。 具体目标2.2：影响反馈学习的因素。我们提供了一个更直接的测试多巴胺能介导的事件相关的潜在信号响应反馈信息（ERN）通过管理多巴胺D2受体激动剂/拮抗剂，这应该有解离的影响，这些信号根据我们的模型。我们还测试了情绪诱导是否可以改变反馈反应的平衡，ERP的测量。最后，我们尝试通过对儿童的协调执行功能和负反馈学习的研究来理清影响执行功能任务学习的多个因素。