Characterizing neural mechanisms of cognitive control

描述（由申请人提供）：“认知控制”描述了配置、维护和调整一系列处理策略（任务集）的能力，这是灵活的、目标导向行为的基础。这项提议的首要目标是提高我们对调节这种行为灵活性的神经机制的理解。这代表了神经科学中具有重要临床意义的核心挑战，因为许多精神和神经疾病的特征是认知控制受损。我们实现这一目标的总体策略是将认知控制的各种概念分解为实验可处理的组成过程，并利用行为，神经成像和神经破坏技术来探索它们的神经基础和相互关系。作为出发点，我们关注冲突驱动控制（“冲突适应”），这是认知控制的一个组成机制，服务于任务集维护的功能。在这里，由于同时激活不相容的刺激或反应表征而产生的加工冲突的监测被认为是为强化自上而下的偏倚过程（包括当前任务集）提供了一个信号，从而确保偏倚水平与任务难度保持相称。我们追求两个具体目标：第一，更深刻地理解冲突适应本身的神经机制；第二，将这种冲突驱动的控制机制置于其他类型控制过程的更广泛框架中，这些控制过程结合在一起，促进了灵活的行为。两项研究将解决第一个目标。研究1.1将检验冲突驱动控制在多个冲突适应循环的并行架构中组织的假设，这些循环独立解决不同类型的冲突。为此，我们将使用功能磁共振成像（fMRI）和经颅磁刺激（TMS）来定义冲突适应独立不同冲突来源的神经基质，以测试不同的自上而下控制来源是否在解决不同冲突中发挥可解解的因果作用。研究1.2将密切描述冲突适应过程的时间过程。为了解决第二个目标，另外三个研究将评估冲突适应如何与认知控制的其他组成机制相互作用。研究2.1通过将功能磁共振成像与相位和张力冲突水平的正交操作相结合，将短暂冲突适应机制与更持久的控制形式进行对比，来实现这一目标。研究2.2对比了冲突适应的反应性和主动招募的控制，这些控制来自于关于即将到来的冲突的明确线索。最后，研究2.3考察了冲突任务转换范式下，冲突驱动任务集强化的神经机制与任务改变检测和任务集重构的神经机制之间的关系。这个研究项目有可能显著增强我们对人类大脑如何支持灵活的、目标导向的行为的理解，并突出这种能力中可能的失败模式。

DESCRIPTION (provided by applicant): 'Cognitive control' describes the ability to configure, maintain, and adjust sets of processing strategies (task-sets), which underpins flexible, goal-directed behavior. The overarching goal of this proposal is to improve our understanding of the neural mechanisms mediating this behavioral flexibility. This represents a central challenge in the neurosciences that bears major clinical relevance, as many psychiatric and neurological conditions are characterized by impaired cognitive control. Our general strategy for achieving this goal is to fractionate the multifarious concept of cognitive control into experimentally tractable component processes, and to harness behavioral, neuroimaging, and neuro-disruptive techniques to probe their neural underpinnings and interrelations. As a point of departure we focus on conflict-driven control ('conflict adaptation'), a component mechanism of cognitive control that serves the function of task-set maintenance. Here, the monitoring of processing conflicts, arising from simultaneous activation of incompatible stimulus or response representations, is thought to provide a signal for reinforcing the top-down biasing processes that comprise the current task-set, thus ensuring that levels of biasing remain commensurate with task difficulty. We pursue two specific aims: first, to gain a more profound understanding of the neural mechanisms underlying conflict adaptation itself, and second, to position this conflict-driven control mechanism within the wider framework of other types of control processes that, in combination, facilitate flexible behavior. Two studies will address the first aim. Study 1.1 will examine the hypothesis that conflict-driven control is organized in a parallel architecture of multiple conflict adaptation loops, which resolve different types of conflict independently. For this purpose, we will define neural substrates of conflict adaptation to independently varied sources of conflict, using functional magnetic resonance imaging (fMRI), followed by fMRI-guided transcranial magnetic stimulation (TMS), to test whether distinct sources of top-down control play dissociable causal roles in resolving different conflicts. Study 1.2 will closely characterize the time-course of conflict adaptation processes. To address the second aim, three additional studies will assess how conflict adaptation interacts with other component mechanisms of cognitive control. Study 2.1 pursues this goal by contrasting the transient conflict adaptation mechanism with a more sustained form of control, by combining fMRI with an orthogonal manipulation of phasic and tonic levels of conflict. Study 2.2 contrasts the reactive nature of conflict adaptation with proactively recruited control, derived from explicit cues regarding forthcoming conflict. Finally, study 2.3 examines the relation between neural mechanisms underlying conflict-driven reinforcement of task-set with those that mediate detection of task-change and task-set reconfiguration, in a conflict task-switching paradigm. This research program has the potential to significantly enhance our understanding of how the human brain supports flexible, goal-directed behavior, and to highlight possible failure modes in this ability. PUBLIC HEALTH RELEVANCE: The proposed research is designed to elucidate neural mechanisms of 'cognitive control', the ability to generate, maintain, and adjust sets of goal-directed processing strategies, which lies at the heart of the type of flexible behavior that distinguishes humans from other animals, including other primates. We pursue this goal by combining experimental tasks that tax various component processes of cognitive control to differing degrees with measurements of brain activity (and functional connectivity between brain regions), as well as with stimulation techniques that temporarily inhibit function in a specific brain region, so that we can pinpoint which aspect of cognitive control is mediated by which brain region (or which set of interacting brain regions). The knowledge gained from this work will enhance our understanding of how the healthy brain mediates flexible, goal-directed behavior, and will provide more precise ideas of how neural mechanisms of cognitive control might be disrupted in psychiatric and neurological conditions.