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.

根据当前目标和情境灵活调整行为的能力称为认知控制，即 对于适当应对我们生活中面临的各种情况至关重要。这变得非常明显 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，它映射 根据上下文采取行动的提示。当我们采取行动时，我们通常从应用抽象规则开始（例如 早上意味着咖啡），这有助于选择更具体的规则（例如咖啡意味着研磨豆） 更接近动作规范。前额皮质 (PFC)，尤其是 46 和 9/46 区域，对于处理过程至关重要 规则，PFC 神经元已被证明可以代表具体和抽象的规则。这引发了两个 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？ 尽管对于 PFC 的功能组织有两个重要的建议，其中一个建议是前额皮质 基于规则抽象的后验梯度和另一个表明单个神经元有助于 处理多个规则（而不是按地形组织），缺乏电生理学 研究测试这些建议。第二个问题是PFC神经元的不同集合如何灵活地 并根据行为相关规则选择性激活？神经同步可能是一个合适的选择 机制，在同步单元之间动态路由信息。有证据表明，较高的 丘脑序列在皮质区域之间形成间接通路，可以调节皮质振荡和 同步。丘脑内侧核 (MD) 与 PFC 广泛相连，因此与 定位影响 PFC 活动。功能性 MRI 和病变研究表明 MD 发挥着重要作用 一般而言，在规则处理和认知控制中。然而，电生理学方面的研究却很少。 研究探讨了 MD 在认知控制中的作用，但没有一个研究探讨 MD 和 PFC 在认知控制中如何相互作用。 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 如何在功能上组织 (SA#2)，以及 MD 和 PFC 在规则引导行为期间如何交互 (SA#3)。 中心假设是 MD 调节 PFC 神经元之间的信息传递。关键机制 可能涉及 MD 同步代表任务相关规则的 PFC 神经元。为了检验这个假设，我们 同时记录执行基于规则的任务的猴子的 MD 和区域 46 和 9/46 的神经活动。 我们还刺激 MD 来测试 MD 是否对振荡活动、神经同步和 通过 PFC 的信息传输。为了将这项工作转化为人类，我们获取了颅内录音 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 介导认知控制的大规模网络动态。定义认知的基本机制 控制是制定针对认知控制缺陷的有效治疗策略的第一个必要步骤。

项目成果

Topographic organization of connections between prefrontal cortex and mediodorsal thalamus: Evidence for a general principle of indirect thalamic pathways between directly connected cortical areas.

前额皮质和内侧丘脑之间连接的地形组织：直接连接的皮质区域之间间接丘脑通路一般原理的证据。

• 发表时间: 2019
• 影响因子: 5.7
• 作者: Phillips, Jessica M;Fish, Lesenia R;Kambi, Niranjan A;Redinbaugh, Michelle J;Mohanta, Sounak;Kecskemeti, Steven R;Saalmann, Yuri B
• 通讯作者: Saalmann, Yuri B