Hippocampal-orbitofrontal interactions and reward learning

海马-眶额相互作用和奖励学习

• 批准号: 10064645
• 负责人: Joni D Wallis
• 金额: $ 45.5万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-03 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10064645
• 关键词: Affect; Alpha Rhythm; Anterior; Anxiety; Area; Brain; Cognitive; Communication; Data; Decision Making; Dorsal; Environment; Evolution; Frequencies; Functional disorder; Future; Goals; Grant; Habits; Hippocampus (Brain); Lead; Learning; Maps; Measures; Mediating; Mental Depression; Methodology; Methods; Modeling; Mood Disorders; Neurons; Obsessive-Compulsive Disorder; Pathway interactions; Performance; Post-Traumatic Stress Disorders; Primates; Process; Property; Psychiatry; Psychological reinforcement; Psychopathology; Research; Rewards; Rodent; Role; Schizophrenia; Signal Transduction; Stimulus; Structure; Symptoms; System; Testing; Therapeutic; Therapeutic Intervention; Theta Rhythm; Work; addiction; base; electrical microstimulation; environmental change; flexibility; high dimensionality; improved; learning strategy; microstimulation; neuromechanism; neuropsychiatric disorder; relating to nervous system; response; skills; time use

Project summary (<30 lines) Dysfunction of both the hippocampus and the orbitofrontal cortex have been implicated in a wide variety of neuropsychiatric disorders, including obsessive-compulsive disorder, mood disorders and addiction. However, their exact contribution remains unclear. A major problem is that most research on hippocampal mechanisms is derived from rodent work. However, the structure of the hippocampus has undergone dramatic changes across the course of evolution, particularly in those parts associated with psychopathologies. This necessitates the use of primate models, but there have been few studies of hippocampus in the primate. The current grant will investigate the neuronal properties of hippocampus in the primate and determine how it interacts with orbitofrontal cortex. The theoretical framework that we will employ is derived from computational psychiatry, with a particular focus on how the computational processes underlying reinforcement learning might contribute to neuropsychiatric disease. Our hypothesis is that both hippocampus and orbitofrontal cortex make critical contributions to model-based reinforcement learning, whereby hippocampus is responsible for constructing the cognitive map that instantiates the neural representation of the task model, and orbitofrontal cortex is responsible for using the cognitive map to generate reward predictions that can be used to guide decision-making. To test this hypothesis, we will use a combination of high-channel count neuronal recordings and electrical microstimulation. We will record from single neurons in the hippocampus during performance of a reward-based learning task and examine whether hippocampal neurons show value place tuning. We will then examine how hippocampus might communicate this information to orbitofrontal cortex by recording from both structures simultaneously. Our prediction is that this communication will be mediated via synchronization of theta rhythms. However, such measures are correlative. Establishing a causal role for neural rhythms has proven challenging, since it is difficult to manipulate a specific neuronal rhythm without affecting other neuronal rhythms and/or neuronal firing rates. We have recently developed a closed-loop approach, which involves recording rhythms in real-time and using those signals to control the application of electrical microstimulation. This allows us to disrupt a neuronal rhythm of a specific frequency. We will use this method to examine whether there is a causal role for the theta oscillation in reward-based learning. Taken together, the results of this proposal will provide convergent correlative and causal evidence for the role of hippocampus and orbitofrontal cortex in reward-based learning and the mechanism by which they communicate. This will help lay the groundwork for future potential therapeutic approaches for frontolimbic dysfunction based on closed-loop microstimulation.

项目摘要（<30 行） 海马体和眶额皮质的功能障碍与多种疾病有关 神经精神疾病，包括强迫症、情绪障碍和成瘾。然而， 他们的具体贡献仍不清楚。一个主要问题是大多数关于海马机制的研究 来自啮齿动物的工作。然而海马体的结构却发生了巨大的变化 整个进化过程，特别是与精神病理学相关的部分。这需要 使用灵长类动物模型，但对灵长类动物海马体的研究很少。目前的补助金 将研究灵长类动物海马体的神经元特性，并确定它如何与 眶额皮质。 我们将采用的理论框架源自计算精神病学，特别关注 关于强化学习背后的计算过程如何有助于神经精神病学 疾病。我们的假设是海马体和眶额皮质都对 基于模型的强化学习，海马体负责构建认知图 实例化任务模型的神经表示，眶额皮层负责使用 认知图生成可用于指导决策的奖励预测。为了测试这个 假设，我们将使用高通道数神经元记录和电学的组合 微刺激。 我们将在执行基于奖励的学习任务期间记录海马体中的单个神经元 并检查海马神经元是否表现出价值位置调节。然后我们将检查海马体如何 可能会通过同时从两个结构进行记录来将此信息传达给眶额皮层。 我们的预测是，这种交流将通过 θ 节律的同步来介导。然而，这样的 措施是相关的。事实证明，建立神经节律的因果作用具有挑战性，因为它是 难以操纵特定的神经元节律而不影响其他神经元节律和/或神经元 发射率。我们最近开发了一种闭环方法，其中涉及实时记录节奏 并使用这些信号来控制电微刺激的应用。这使我们能够破坏 特定频率的神经节律。我们将使用这种方法来检查是否存在因果关系 基于奖励的学习中的 theta 振荡。 总而言之，该提案的结果将为该角色提供收敛的相关性和因果性证据 海马体和眶额皮质在基于奖励的学习中的作用及其机制 交流。这将有助于为未来额边缘的潜在治疗方法奠定基础 基于闭环微刺激的功能障碍。