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.

项目概要/摘要 适应性行为需要能够牢记当前的任务并避免分心（认知 稳定性），以及更新任务集以响应不断变化的需求（认知灵活性）。 稳定性和灵活性是互补的，但处理模式相反，因为更高的稳定性是以牺牲 灵活性较低，反之亦然，稳定或灵活的心理状态本质上都不是有益的； 相反，它是一个人的灵活性水平对不同环境需求的适应——或元灵活性—— 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（且知之甚少）的“认知控制困境”，并且这种能力是严重的。 因此，了解介导元灵活性的神经机制对于基础和临床脑科学都具有重要意义。 外部（例如药物）引起的灵活性设定点变化的研究已经取得了一些成功，但这并不是 目前已知大脑如何产生策略元灵活性，即学习使一个人的灵活性水平适应 而新兴的行为文献表明，人们会策略性地调整自己的准备状态，以适应不断变化的环境。 根据上下文切换可能性的变化来切换任务，迄今为止还没有研究检查神经网络 这些动态的、习得的认知灵活性变化背后的机制因此是本研究的总体目标。 我们的建议是为了培养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）认知灵活性学习方案，采用功能性磁共振成像 (fMRI) 和 一套尖端的分析方法，包括大脑状态“pinging”和表征相似性（RSA）， 在目标 2 中，我们将继续进行多体素模式 (MVPA) 和动态功能连接 (dFC) 分析。 确定指导上述转换准备战略转变机制的学习过程。 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)，用于测试“增量”强化学习 (RL)（研究 3 和 4）和间歇性恢复（研究 5）可能有助于指导战略元灵活性。 战略元灵活性的基本大脑机制，在目标 3 中，我们检查其潜在的临床意义： 跨诊断认知内表型，通过利用大规模在线数据收集将个体联系起来 临床相关自我报告测量中的策略元灵活性差异（研究 6）。 为认知元灵活性的潜在计算精神病学奠定基础总而言之，该提案是 第一个针对策略元灵活性（即适应能力）的神经认知机制的系统研究计划 这个创新项目将显着增强我们对环境的理解。 如何调节任务切换，并帮助识别健康和疾病中元灵活性的潜在失败模式。