Neural Mechanisms of Cognitive Meta-Flexibility

项目摘要/摘要 适应性行为需要在头脑中记住当前的任务，并使其免受分心(认知 稳定性)，以及根据不断变化的需求更新任务集(认知灵活性)。认知 稳定性和灵活性是互补的，但处理模式是对立的，因为更大的稳定性是以 灵活性较低，反之亦然。重要的是，稳定或灵活的心理状态从本质上来说都不是有益的； 相反，这是一个人的灵活性水平适应不同的环境要求--或元灵活性--的结果 产生最佳认知。因此，在稳定性/灵活性的权衡中采用上下文最优的设置点被认为是一种具有挑战性的(也是很难理解的)“认知控制困境”，这种能力是严重的 在许多精神疾病中受损。因此，了解调节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 而外界(例如，药物)引起的灵活性设定值的变化已经得到了一些成功的研究，但还没有 目前已知大脑如何产生策略性元灵活性，即学习调整一个人的灵活性水平以适应 不断变化的环境。虽然新兴的行为文学表明，人们会战略性地调整他们的准备，以适应 转换任务与语境转换可能性的变化一致，到目前为止还没有研究检查神经 这些动态、习得的认知灵活性变化背后的机制。因此，这一总体目标是 建议的目的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，我们通过结合主动性(研究1)和元灵活性来描绘元灵活性的神经位置和机制 反应性(研究2)认知灵活性学习协议与功能磁共振成像(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，我们然后继续 确定指导上述交换准备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、神经记忆恢复的多变量测量以及基于模型的功能磁共振成像引导 经颅磁刺激(TMS)以测试“增量”强化学习(RL)(研究3和 4)和间歇性恢复(研究5)可能有助于引导策略元灵活性。在建立了 策略性元灵活性的基本脑机制，在目标3中，我们然后检验其潜在的临床意义 一种跨诊断的认知内表型，通过利用大规模在线数据收集将个人联系起来 策略元灵活性与临床相关的自我报告测量差异的差异(研究6)。因此，我们 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 首次系统研究策略性元灵活性、适应能力的神经认知机制 随时准备交换，以适应不断变化的环境。这一创新项目将极大地提高我们对 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。

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.