Prefrontal cortico-thalamic dynamics in cognitive control

认知控制中的前额皮质丘脑动力学

• 批准号: 9925256
• 负责人: Yuri B Saalmann
• 金额: $ 37.61万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9925256
• 关键词: Anatomy; Anterior; Area; Attention deficit hyperactivity disorder; Behavior; Behavioral; Brain; Cells; Coffee; Cognition; Cues; Data; Diffusion Magnetic Resonance Imaging; Electrocorticogram; Electrodes; Electrophysiology (science); Epilepsy; Etiology; Face; Feedback; Functional Magnetic Resonance Imaging; Goals; Health; Human; Impaired cognition; Impairment; Individual; Knowledge; Lesion; Life; Link; Macaca; Maps; Measures; Medial Dorsal Nucleus; Mediating; Monkeys; Nature; Neurons; Obsessive-Compulsive Disorder; Pathway interactions; Patients; Physiology; Play; Positioning Attribute; Prefrontal Cortex; Primates; Public Health; Research; Role; Route; Schizophrenia; Short-Term Memory; Signal Transduction; Site; Source; Stimulus; Structure; Testing; Thalamic Nuclei; Thalamic structure; Time; Translating; Work; base; bean; cognitive control; cognitive process; density; effective therapy; experimental study; flexibility; implantation; neuromechanism; neurotransmission; operation; relating to nervous system; response; transmission process; treatment strategy

The ability to flexibly adapt behavior based on current goals and context is called cognitive control, which is essential for responding appropriately to the diverse situations we face in life. This becomes strikingly clear when cognitive control is impaired, as in schizophrenia, obsessive-compulsive disorder and attention-deficit hyperactivity disorder. An important implementation of cognitive control is the application of rules, which map cues to actions according to context. When we carry out actions, we often start by applying abstract rules (e.g. morning means coffee), which aid in the selection of more concrete rules (e.g. coffee means grind beans) closer to action specification. Prefrontal cortex (PFC), especially areas 46 and 9/46, is vital for processing rules, and PFC neurons have been shown to represent concrete and abstract rules. This raises two fundamental questions. First, how are neurons that represent abstract and concrete rules organized in PFC? Although there are two prominent proposals for the functional organization of PFC, one suggesting an anterior- posterior gradient based on rule abstraction and the other suggesting individual neurons contribute to the processing of multiple rules (instead of being topographically organized), there is a lack of electrophysiology studies testing these proposals. The second question is how are distinct ensembles of PFC neurons flexibly and selectively activated based on behaviorally relevant rules? Neural synchrony may be a suitable selection mechanism, dynamically routing information between synchronized cells. Evidence suggests that the higher- order thalamus, which forms indirect pathways between cortical areas, can regulate cortical oscillations and synchrony. The mediodorsal thalamic nucleus (MD) is extensively connected with PFC and is thus well positioned to influence PFC activity. Functional MRI and lesion studies suggest that MD plays an important role in rule processing and cognitive control in general. However, there have been very few electrophysiology studies probing the role of MD in cognitive control, and none have probed how MD and PFC interact in primates. The goal of the proposed research is to characterize how MD contributes to rule processing (SA#1), how PFC is functionally organized (SA#2), and how MD and PFC interact during rule-guided behavior (SA#3). The central hypothesis is that MD regulates information transmission between PFC neurons. A key mechanism may involve MD synchronizing PFC neurons that represent task-relevant rules. To test this hypothesis, we simultaneously record neural activity in MD and areas 46 and 9/46 of monkeys performing a rule-based task. We also stimulate MD to test whether MD has a causal influence on oscillatory activity, neural synchrony and information transmission across PFC. To translate this work to humans, we acquire intracranial recordings in epilepsy patients performing the same rule-based task. The proposed research will advance our understanding of the large-scale network dynamics that mediate cognitive control. Defining the basic mechanisms of cognitive control is a first necessary step in developing effective treatment strategies for cognitive control deficits.

根据当前目标和背景灵活调整行为的能力被称为认知控制，这是 对于恰当地应对我们生活中面临的各种情况是必不可少的。这一点变得非常清楚 当认知控制受损时，如精神分裂症、强迫症和注意力缺陷 多动症。认知控制的一个重要实现是规则的应用，这些规则映射 根据上下文提示行动。当我们采取行动时，我们通常从应用抽象的规则开始(例如 早晨意味着咖啡)，这有助于选择更具体的规则(例如咖啡意味着研磨豆子) 更接近动作规范。前额叶皮质(PFC)，特别是46区和9/46区，对脑加工至关重要 规则，而PFC神经元已被证明代表具体和抽象的规则。这引发了两个问题 基本问题。首先，代表抽象和具体规则的神经元在PFC中是如何组织的？ 尽管关于PFC的职能组织有两个突出的建议，一个建议是前置-- 一种是基于规则提取的后验梯度，另一种是单个神经元对 处理多个规则(而不是按地形组织)，缺乏电生理学 对这些建议进行测试的研究。第二个问题是不同的PFC神经元集合是如何灵活的 并根据行为相关规则有选择地激活？神经同步性可能是一个合适的选择 机制，在同步信元之间动态地路由信息。有证据表明，越高- 在皮质区域之间形成间接通路的有序丘脑，可以调节皮质振荡和 同步性。丘脑内侧背核(MD)与前额叶核(PFC)有广泛的联系，因此 定位于影响PFC活动。功能磁共振成像和病变研究表明MD在脑血管病变中起重要作用 一般在规则处理和认知控制方面。然而，电生理学的研究非常少。 探讨MD在认知控制中的作用的研究，没有探讨MD和PFC是如何相互作用的 灵长类动物。拟议研究的目标是描述MD如何促进规则处理(SA#1)， PFC是如何在功能上组织的(SA#2)，以及MD和PFC在规则引导行为期间如何交互(SA#3)。 中心假说是MD调节PFC神经元之间的信息传递。一个关键的机制 可能涉及MD同步代表任务相关规则的PFC神经元。为了检验这一假设，我们 同时记录执行基于规则的任务的猴子在MD和46区和9/46区的神经活动。 我们还刺激MD以测试MD是否对振荡活动、神经同步性和 通过PFC进行信息传输。为了将这项工作转移到人类身上，我们在 癫痫患者执行相同的基于规则的任务。拟议的研究将增进我们的理解 调节认知控制的大规模网络动态。界定认知的基本机制 控制是开发有效的认知控制缺陷治疗策略的第一个必要步骤。