Prefrontal cortico-thalamic dynamics in cognitive control

根据当前目标和背景灵活调整行为的能力称为认知控制， 这对于我们在生活中面对的各种情况做出适当反应至关重要。这一点非常清楚 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， 根据上下文提示动作。当我们采取行动时，我们通常从应用抽象规则开始（例如， 早晨意味着咖啡），这有助于选择更具体的规则（例如，咖啡意味着磨豆） 更接近行动规范。前额叶皮层（PFC），特别是46区和9/46区，对处理信息至关重要 PFC神经元已经被证明可以代表具体和抽象的规则。这引起了两个 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？ 虽然有两个突出的建议，为PFC的功能组织，一个建议前- 后梯度的基础上的规则抽象和其他建议个别神经元有助于 处理多个规则（而不是地形组织），缺乏电生理学 研究测试这些建议。第二个问题是不同的PFC神经元集合如何灵活地 并根据行为相关的规则选择性地激活？神经同步可能是一个合适的选择 机制，在同步小区之间动态路由信息。有证据表明，越高- 顺序丘脑，形成皮层区域之间的间接通路，可以调节皮层振荡， 同步性丘脑背内侧核（MD）与前额叶皮层有广泛的联系， 能够影响PFC的活动。功能磁共振成像和病变研究表明，MD起着重要作用， 在规则处理和认知控制中的作用。然而，很少有电生理学 研究探讨MD在认知控制中的作用，没有人探讨MD和PFC如何相互作用， 灵长类动物拟议研究的目标是表征MD如何有助于规则处理（SA#1）， PFC是如何在功能上组织的（SA#2），以及MD和PFC在规则引导的行为中如何相互作用（SA#3）。 核心假设是MD调节PFC神经元之间的信息传递。一个关键机制 可能涉及MD同步代表任务相关规则的PFC神经元。为了验证这个假设，我们 同时记录执行基于规则任务的猴子的MD和区域46和9/46中的神经活动。 我们还刺激MD，以测试MD是否对振荡活动、神经同步性和 为了将这项工作转化为人类，我们获得了颅内记录， 癫痫患者执行相同的基于规则的任务。拟议中的研究将促进我们的理解 大规模的网络动态，调解认知控制。定义认知的基本机制 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。

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.