Basal ganglia and dopamine contributions to feedback-based learning

描述（由申请人提供）：本提案的主要目的是了解支持增量式反馈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神经节（BG）-主要是纹状体及其多巴胺能传入。相比之下，内侧颞叶（MTL）中的一个独特而独立的记忆系统被认为支持对单次试验事件的快速形成的记忆。然而，最近的研究表明，这种二分法可能过于简单，在许多情况下，BG和MTL都有助于学习。因此，基本的问题仍然存在的情况下，这些系统中的每一个支持学习和他们的参与的知识表示的影响。跨电生理学数据，计算建模和人类神经心理学的桥梁，拟议的研究旨在测试的假设，驱动学习依赖于一个系统或其他的一个关键因素是响应的时机-偶然反馈。本文的研究试图通过系统地调查反馈的时间（即时与延迟）如何调节学习和记忆的不同方面来验证这一假设。我们的模型系统是健康的老年人和帕金森病患者，他们患有BG功能中断，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病患者基于反馈的学习来进一步研究慢性和急性多巴胺扰动。最后，我们的目标是确定在不同的延迟条件下所涉及的认知机制，比较增量和情景学习。由此产生的研究结果，预计将提高我们的认知和神经系统支持反馈为基础的学习，以及这些是如何调制BG功能障碍和多巴胺能机制的理解。公共卫生相关性：帕金森病的特征是一系列的学习缺陷。由此产生的结果将提供深入了解这些缺陷的性质和可能原因，以及它们如何受到药物的影响。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有关，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.