Hippocampal-orbitofrontal interactions and reward learning

项目摘要(&lt；30行) 海马体和眶前叶皮质的功能障碍与许多不同的 神经精神障碍，包括强迫症、情绪障碍和成瘾。然而， 他们的具体贡献尚不清楚。一个主要的问题是，大多数关于海马体机制的研究 是从啮齿动物的工作中衍生出来的。然而，海马体的结构发生了戏剧性的变化 在进化过程中，特别是在那些与精神病相关的部分。这是必要的 灵长类动物模型的使用，但关于灵长类动物海马体的研究很少。目前的拨款 将研究灵长类动物海马区的神经元特性，并确定它如何与 眶前叶皮质。 我们将使用的理论框架来自计算精神病学，并特别关注 强化学习背后的计算过程如何可能有助于神经精神病学 疾病。我们的假设是，海马体和眼眶前额叶皮质都对 基于模型的强化学习，其中海马体负责构建认知地图 这实例化了任务模型的神经表示，而眶前皮质负责使用 产生可用于指导决策的奖励预测的认知图。为了测试这一点 假设，我们将使用高通道计数神经元记录和电信号的组合 微刺激。 我们将在基于奖励的学习任务中记录海马区的单个神经元 并检查海马神经元是否显示出有价值的位置调节。然后我们将研究海马体是如何 可能会通过同时从两个结构进行记录来将这一信息传递到眶前皮质。 我们的预测是，这种交流将通过theta节律的同步来调节。然而，这样的 措施是相互关联的。确定神经节律的因果作用被证明是具有挑战性的，因为它 很难在不影响其他神经元节律和/或神经元的情况下操纵特定的神经元节律 射击率。我们最近开发了一种闭环方法，包括实时记录节奏 并使用这些信号来控制电微刺激的应用。这允许我们扰乱一个 特定频率的神经元节律。我们将使用这种方法来检验是否存在因果关系 基于奖励的学习中的theta振荡。 综上所述，这一提议的结果将为这一角色提供趋同的相关和因果证据 奖赏学习中海马区和眶前叶皮质的变化及其机制 交流。这将有助于为未来额叶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。

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.