Characterizing neural mechanisms of cognitive control

描述(申请人提供)：我们研究项目的总体目的是了解认知控制的大脑机制，即根据内部目标灵活调整思想和行为的能力。前一个授权期的工作集中于信息处理中的冲突(例如，在繁忙的十字路口如何最好地驶入预期车道的不确定性)如何立即将注意力重新集中在手头的任务上(冲突控制)。在这份续签申请中，我们广泛地询问：下一次您接近那个十字路口时会发生什么？你会记住你以前遇到的困难，并从一开始就以高度的注意力来处理它吗？认知控制和记忆过程之间的这种相互作用渗透到我们的日常生活中，未能将情景需求与注意力状态适当匹配是许多令人衰弱的精神障碍的关键特征，如精神分裂症。然而，线索(如交叉点)和适当的控制状态之间的关联是如何形成的，以及不同控制操作对后续记忆的影响目前还不太清楚，部分原因是控制是历史上定义的，与良好学习的反应(“意志与习惯”)相反。因此，这项建议的目的是表征认知控制和联想过程的相互作用，以改进目前大脑如何支持适应行为的模型，并使新的方法能够理解临床领域中认知控制的失败。为此，我们从两个方面考察了控制-记忆的交互作用：第一，具体目标1考察学习如何驱动认知控制的分配。换句话说，繁忙的交叉口如何与更高的控制状态相关联？我们使用计算建模、功能磁共振成像和功能磁共振成像引导的TMS方法来表征大脑如何学习以适应不断变化的需求(研究1)，并直接对比将线索与控制状态(上下文控制学习)联系起来的神经机制与支持经典刺激-刺激和刺激-反应学习的神经机制(研究2和3)。第二，特定目标2描述了认知控制过程是如何影响记忆的。例如，在克服困难之后，你是否更有可能记住有关十字路口的关键细节？具体地说，我们将评估三种关键的认知控制操作(冲突控制、更新和反应抑制)对记忆编码的影响，方法是让参与者对不同的刺激执行这些操作，然后通过意外记忆测试测试他们对这些刺激的识别(研究4-6)。将这种方法与功能磁共振成像相结合，我们可以通过对比成功(随后记住)和不成功(随后忘记)编码任务相关和任务无关刺激的神经签名作为控制状态的函数，来解析将特定控制操作与记忆联系起来的大脑机制。这一创新项目将显著提高我们对人脑如何促进上下文敏感的受控行为的理解，并深入了解这种能力可能会如何失败。

DESCRIPTION (provided by applicant): The overall purpose of our research program is to understand the brain mechanisms of cognitive control, the ability to flexibly adapt thoughts and behavior in line with internal goals. Work in the previous grant period has focused on how conflicts in information processing (e.g., uncertainty over how to best steer into your intended lane at a busy intersection) can lead to an immediate re-focusing of attention on the task at hand (conflict- control). In this renewal application, we ask broadly: what happens the next time you approach that intersection? Will you remember your previous difficulties and approach it with a heightened focus of attention to start with? This type of interaction between cognitive control and memory processes pervades our daily lives, and a failure to appropriately match situational demands with attentional states is a key feature of many debilitating psychiatric disorders, such as schizophrenia. However, how associations are formed between cues (e.g., the intersection) and appropriate control states, and what the consequences are of different control operations for subsequent memory, is presently poorly understood, owing in part to control being defined historically in opposition to well-learned responses ("will vs. habit"). Therefore, the goal of this proposal is to characterize the interaction of cognitive control and associative processes in order to improve current models of how the brain supports adaptive behavior, and to enable new approaches for understanding failures of cognitive control in the clinical domain. To this end, we examine control-memory interactions from two directions: first, specific aim 1 investigates how learning drives the allocation of cognitive control. In other words how does the busy intersection become associated with a heightened control state? We use computational modeling, fMRI, and fMRI-guided TMS approaches to characterize how the brain learns to adapt control settings to changing demands (study 1), and to directly contrast the neural mechanisms that link cues to control states (context-control learning) with those supporting classic stimulus-stimulus and stimulus- response learning (studies 2 and 3). Second, specific aim 2 characterizes how cognitive control processes affect memory. E.g., are you more likely to remember key details about the intersection after you had to overcome difficulty there? Specifically, we will assess the impact of three crucial cognitive control operations (conflict-control, updating, and response inhibition) on memory encoding, by having participants perform these operations on different stimuli and subsequently testing their recognition of these stimuli i surprise memory tests (studies 4-6). Pairing this approach with fMRI allows us to parse the brain mechanisms that link specific control operations to memory by contrasting the neural signatures of successful (subsequently remembered) vs. unsuccessful (subsequently forgotten) encoding of task-relevant and task-irrelevant stimuli as a function of control state. This innovative projec is set to significantly improve our understanding of how the human brain facilitates context-sensitive, controlled behavior, and to gain insight into how this ability may fail.