Basal ganglia and dopamine contributions to feedback-based learning

描述(由申请人提供)：本提案的广泛目标是了解支持递增的、基于反馈的学习的认知和神经系统。最近的证据表明，这种类型的学习依赖于基底节(BG)--主要是纹状体及其多巴胺能传入。相比之下，内侧颞叶(MTL)中独特而独立的记忆系统被认为支持对单次试验情节的快速形成记忆。然而，最近的研究表明，这种二分法可能过于简单化，而且在许多情况下，BG和MTL都有助于学习。因此，这些系统中的每一个在什么情况下支持学习，以及它们的参与对知识表示的影响等基本问题仍然存在。这项拟议的研究跨越了电生理数据、计算模型和人类神经心理学，旨在测试这一假设，即驱动学习依赖于一个或另一个系统的关键因素是响应条件反馈的时机。这里的研究试图通过系统地研究反馈的时间(即时和延迟)如何调节学习和记忆的不同方面来检验这一假说。我们的模型系统是健康的老年人和帕金森氏症患者，他们患有BG功能障碍，但MTL功能完整。我们将通过研究多巴胺能药物如何调节帕金森患者基于反馈的学习来进一步检查慢性和急性多巴胺扰动。最后，我们的目标是确定不同延迟条件下涉及的认知机制，比较增量学习和情景学习。这些结果有望增强我们对支持基于反馈的学习的认知和神经系统的理解，以及这些系统是如何受到BG功能障碍和多巴胺能机制的调节的。公共卫生相关性：帕金森氏症的特点是一系列学习障碍。由此产生的发现将提供对这些缺陷的性质和可能的原因的洞察，以及药物如何影响它们。了解基于反馈的学习的基本机制也与影响大部分人群的其他疾病相关，如阿尔茨海默病、抑郁症和精神分裂症--所有这些疾病的特征都是学习和记忆问题。通过了解人们如何因反馈信息的变化而以不同的方式学习，以及大脑化学如何影响这种学习，我们就可以更好地了解如何帮助那些已经患有此类疾病的人，并为未来更好的治疗做出贡献。

DESCRIPTION (provided by applicant): The broad aim of this proposal is to understand the cognitive and neural systems that support incremental, feedback-based learning. Recent evidence suggests that this type of learning depends on the basal ganglia (BG) - primarily the striatum and its dopaminergic afferents. By contrast, a distinct and independent memory system in the medial temporal lobe (MTL) is thought to support rapidly formed memories of single-trial episodes. However, recent studies have shown that this dichotomy may be oversimplified, and that in many cases the BG and the MTL both contribute to learning. Thus, fundamental questions remain regarding the circumstances under which each of these systems support learning and the implications of their involvement for the representation of knowledge. Bridging across electrophysiological data, computational modeling, and human neuropsychology, the proposed research aims to test the hypothesis that a critical factor driving learning to depend on one system or the other is the timing of response-contingent feedback. The studies herein seek to test this hypothesis by systematically investigating how the timing of feedback (immediate vs. delayed) modulates different aspects of learning and memory. Our model system is healthy older adults and individuals with Parkinson's disease, who suffer from disrupted BG function but have intact MTL function. We will further examine both chronic and acute dopamine perturbations by examining how dopaminergic medication modulates feedback-based learning in Parkinson's patients. Finally, we aim to determine the cognitive mechanisms involved under different delay conditions, comparing incremental and episodic learning. The resulting findings are expected to enhance our understanding of the cognitive and neural systems supporting feedback-based learning, and how these are modulated by BG dysfunction and dopaminergic mechanisms. PUBLIC HEALTH RELEVANCE: Parkinson's disease is characterized by a range of learning deficits. The resulting findings will provide insight into the nature, and possible cause, of these deficits, as well as how they are impacted by medication. Understanding the basic mechanisms of feedback-based learning is also relevant to other diseases that affect large segments of the population, such as Alzheimer's disease, depression, and schizophrenia - all characterized by learning and memory problems. By understanding how people learn in different ways as a result of changes in feedback information and how brain chemistry affects this learning, we can better understand how to help those already suffering from such diseases and contribute to better treatments in the future.