Neural Mechanisms of Cognitive Meta-Flexibility

认知元灵活性的神经机制

• 批准号: 10334552
• 负责人: Tobias Egner
• 金额: $ 39.58万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-04 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10334552
• 关键词: Adaptive Behaviors; Adopted; Behavioral; Brain; Brain imaging; Brain region; Classification; Clinical; Cognition; Cognitive; Cues; Data; Data Collection; Disease; Episodic memory; Failure; Fostering; Foundations; Functional Magnetic Resonance Imaging; Goals; Health; Human; Impaired cognition; Impairment; Individual; Individual Differences; Learning; Life; Literature; Magnetism; Measurement; Measures; Mediating; Memory; Mental disorders; Mind; Modeling; Nature; Neurocognitive; Parietal; Patient Self-Report; Patients; Pattern; Persons; Pharmaceutical Preparations; Play; Process; Protocols documentation; Psychiatry; Psychological reinforcement; Readiness; Research; Retrieval; Role; Sampling; Science; Short-Term Memory; Site; Stimulus; Sum; Symptoms; Testing; Time; Transcranial magnetic stimulation; Update; Wit; adjudicate; base; clinically relevant; clinically significant; cognitive ability; cognitive control; cost; distraction; endophenotype; flexibility; image guided; imaging study; innovation; learned behavior; mental state; neural patterning; neuromechanism; operation; patient population; programs; relating to nervous system; response; success; translational potential

Project Summary/Abstract Adaptive behavior requires the ability to keep a current task set in mind and shield it from distraction (cognitive stability), as well as to update task sets in response to changing requirements (cognitive flexibility). Cognitive stability and flexibility are complementary but opponent processing modes, as greater stability comes at the cost of lower flexibility, and vice versa. Importantly, neither a stable nor a flexible mental state is inherently beneficial; rather, it is the adaptation of one’s flexibility level to varying environmental demands – or meta-flexibility - that produces optimal cognition. Accordingly, adopting a contextually optimal set point in the stability/flexibility trade-off is considered a challenging (and poorly understood) “cognitive control dilemma”, and this ability is severely impaired in many psychiatric disorders. Therefore, understanding the neural mechanisms that mediate meta-flexibility is of great significance to both basic and clinical brain science. However, whereas individual differences and externally (e.g., drug-) induced changes in flexibility set points have been studied with some success, it is not presently known how the brain produces strategic meta-flexibility, i.e., learning to adapt one’s flexibility level to changing contexts. While a budding behavioral literature shows that people strategically adapt their readiness to switch tasks in line with changes in contextual switch-likelihood, no study to date has examined the neural mechanisms underlying these dynamic, learned changes in cognitive flexibility. Therefore, the overall goal of this proposal is to foster a new understanding of strategic meta-flexibility. We triangulate this goal via 3 strategic aims: in aim 1 we delineate the neural loci and mechanisms of meta-flexibility by combining proactive (Study 1) and reactive (Study 2) cognitive flexibility learning protocols with functional magnetic resonance imaging (fMRI) and a suite of cutting-edge analysis approaches, including brain state “pinging” and representational similarity (RSA), multivoxel pattern (MVPA), and dynamic functional connectivity (dFC) analyses. In aim 2, we then move on to determine the learning processes that guide the above mechanisms of strategic shifts in switch-readiness. Here, we use model-based fMRI, multivariate measures of neural memory reinstatement, and fMRI-guided model-based transcranial magnetic stimulation (TMS) to test how both “incremental” reinforcement learning (RL) (Studies 3 and 4) and episodic reinstatement (Study 5) may contribute to guiding strategic meta-flexibility. Having established the basic brain mechanisms of strategic meta-flexibility, in aim 3 we then examine its potential clinical significance as a transdiagnostic cognitive endophenotype, by leveraging large-scale online data collection to relate individual differences in strategic meta-flexibility to variance in clinically relevant self-report measures (Study 6). We thus lay the foundation for a potential computational psychiatry of cognitive meta-flexibility. In sum, this proposal is the first systematic research program into neurocognitive mechanisms of strategic meta-flexibility, the ability to adapt switch-readiness to suit changing contexts. This innovative project will significantly enhance our understanding of how task-switching is regulated, and help identify potential failure modes of meta-flexibility in health and disease.

项目摘要/摘要 自适应行为需要牢记当前任务并将其避免分心的能力（认知 稳定性），以及以响应不断变化的要求（认知灵活性）来更新任务集。 稳定性和灵活性是完整的，但是选项处理模式，因为以更高的稳定性为代价 灵活性较低，反之亦然。重要的是，稳定或灵活的精神状态都不是天生有益的。 相反，适应一个人的灵活性水平来改变环​​境需求（或元屈曲度） 产生最佳认知。根据以下内容，在稳定/灵活性权衡中适应上下文最佳的设定点被认为是一个挑战（并且理解很少）“认知控制困境”，这种能力严重是 许多精神疾病受损。因此，了解介导荟萃的神经力学对基础和临床脑科学都具有重要意义。但是，尽管个体差异 在外部（例如，药物）诱导的灵活性设定点的变化已经研究了，并没有 目前知道大脑如何产生战略性的元屈服性，即学习适应一个人的灵活性水平 改变上下文。虽然萌芽的行为文献表明，人们从战略上适应了自己的准备 切换任务与上下文开关样式的变化一致，迄今为止尚无研究检查神经 这些动态，学习的认知灵活性变化的机制。因此，总体目标 提案是为了促进对战略性元融合性的新理解。我们通过3个战略目标对此目标进行三角测量： 在AIM 1中，我们通过组合主动（研究1）和 反应性（研究2）具有功能磁共振成像（fMRI）和A的认知灵活性学习方案 尖端分析方法的套件，包括大脑状态“ ping”和代表性相似性（RSA）， 多毒素模式（MVPA）和动态功能连接性（DFC）分析。在AIM 2中，我们继续前进 确定指导上述开关准备方面战略转变机制的学习过程。在这里，我们 使用基于模型的功能磁共振成像，神经膜恢复的多元测量以及基于fMRI指导的模型 经颅磁刺激（TMS）测试如何“增量”增强学习（RL）（研究3和 4）和情节恢复原状（研究5）可能有助于指导战略性元借助性。建立了 战略性元屈服性的基本大脑机制，在AIM 3中，我们将其潜在的临床意义研究为 通过利用大规模的在线数据收集到相关个人 临床相关的自我报告措施中对差异的战略元屈服性差异（研究6）。因此，我们 奠定了认知元屈曲度潜在的计算精神病学的基础。总而言之，该提议是 第一个系统研究计划，用于策略元融合性的神经认知机制，适应能力 开关准备度适合改变上下文。这个创新的项目将大大增强我们对 如何调节任务切换，并有助于确定健康和疾病中元屈服的潜在失败模式。