Neural Mechanisms of Cognitive Meta-Flexibility

认知元灵活性的神经机制

• 批准号: 9906944
• 负责人: Tobias Egner
• 金额: $ 39.97万
• 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/9906944
• 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; 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

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.

项目总结/摘要 适应性行为需要有能力记住当前的任务，并保护它不受干扰（认知）。 稳定性），以及根据不断变化的要求更新任务集（认知灵活性）。认知 稳定性和灵活性是互补的，但相反的处理模式，因为更大的稳定性是以牺牲 灵活性低，反之亦然。重要的是，无论是稳定的还是灵活的心理状态都不是天生有益的; 相反，它是一个人的灵活性水平，以适应不同的环境要求-或元灵活性-， 产生最佳认知。因此，在稳定性/灵活性权衡中采用上下文最佳设定点被认为是具有挑战性的（并且理解不足的）“认知控制困境”，并且这种能力严重地被限制。 在许多精神疾病中受损。因此，了解介导元灵活性的神经机制对基础和临床脑科学都具有重要意义。然而，尽管个体差异 并且在外部（例如，药物）诱导的柔性设定点的变化已经研究了一些成功，但它不是 目前已知大脑如何产生战略元灵活性，即，学习调整自己的灵活性水平， 不断变化的环境虽然一个萌芽的行为文献表明，人们战略性地调整他们的准备， 切换任务与上下文切换可能性的变化一致，迄今为止还没有研究检查神经 认知灵活性中这些动态的、习得的变化背后的机制。因此，这一总体目标 建议是促进对战略元灵活性的新理解。我们通过三个战略目标来实现这一目标： 在目标1中，我们通过结合主动（研究1）和 反应性（研究2）认知灵活性学习协议与功能性磁共振成像（fMRI）和 一套尖端的分析方法，包括大脑状态“ping”和表征相似性（RSA）， 多体素模式（MVPA）和动态功能连接性（dFC）分析。在目标2中，我们继续 确定指导上述转换准备中战略转变机制的学习过程。这里我们 使用基于模型的功能磁共振成像，神经记忆恢复的多变量测量，以及基于功能磁共振成像引导的模型 经颅磁刺激（TMS），以测试“增量”强化学习（RL）（研究3和 4)和情景恢复（研究5）可能有助于指导战略元灵活性。在建立了 基本的大脑机制的战略元灵活性，在目标3，我们然后检查其潜在的临床意义， 一种跨诊断的认知内表型，通过利用大规模的在线数据收集， 在临床相关的自我报告措施中，策略元灵活性对方差的差异（研究6）。我们因此 为认知元灵活性的潜在计算精神病学奠定基础。总而言之，这项建议是 第一个系统的研究计划，进入神经认知机制的战略元灵活性，适应能力， 随时准备切换以适应不断变化的环境。这一创新项目将大大提高我们对 如何调节任务转换，并帮助识别健康和疾病中元灵活性的潜在故障模式。