Aging effects on the neural coding of proactive and reactive cognitive control: Administrative Supplement

项目摘要 这项建议探讨了神经和心理机制，这些机制是公认的下降的基础， 认知控制功能的经验，否则健康的老年人。一个明确的共识， 衰老的神经科学是，与年龄相关的认知控制能力下降反映了神经生物学的变化， 在中脑多巴胺系统的运作中，与位于侧前额叶的目标相互作用， 前扣带皮层（ACC）。目前的提案采用了一种创新的实验性方法， 解决这个问题的方法，通过利用代表性相似性分析（RSA）的方法， 研究认知控制的神经编码以及它如何随着年龄的增长而变化。具体来说，我们利用 RSA测试双重控制机制（DMC）理论框架，该框架假设老年人 在主动控制的参与方面将表现出明显的损害，但相对保留了反应性控制。 控制该项目直接测试这一假设，采用新的理论优化的变体的工作- 马色词Stroop范式，结合RSA方法，探讨其神经机制 与前摄和反应性控制相关，使用多模态神经成像方法， fMRI和EEG研究。这种多模式方法可以对DMC进行系统和全面的测试 框架，以测试主动和被动控制是否有不同的时间动态签名，并涉及 解剖学上分离的神经机制在lPFC和ACC。我们进一步建议，以丰富我们的 了解认知控制功能中与年龄相关的变化机制，通过利用最近的 在评估临床前阿尔茨海默病（AD）和AD相关疾病风险的能力方面取得的进展 通过使用基于血浆的生物标志物来治疗神经变性。通过与Dr. 布莱恩·戈登，瑞安·博格丹博士和苏珊娜·辛德勒博士，我们将利用最先进的方法，包括 单分子阵列（Simoa）和质谱，以全面评估关键的血液生物标志物 与淀粉样蛋白（APOE，β-淀粉样蛋白）、tau（ptau 181）和神经变性（NfL，GFAP）相关，以及 解剖学MRI生物标志物（例如，皮质厚度）。我们建议一项行政补充规定， 为我们获取、处理和严格分析AD相关生物标志物数据提供额外支持。这种补充剂 将极大地提高范围，影响，

Project Summary This proposal explores the neural and psychological mechanisms that underlie the well-established declines in cognitive control function experienced by otherwise healthy older adults. A clear consensus in the cognitive neuroscience of aging is that age-related cognitive control declines reflect neurobiological changes that occur in the functioning of the mid-brain dopamine system, interacting with targets located in the lateral prefrontal cortex (lPFC) and anterior cingulate cortex (ACC). The current proposal adopts an innovative experimental approach to this issue, by leveraging the methodology of representational similarity analysis (RSA), to examine the neural coding of cognitive control and how it changes with advancing age. Specifically, we utilize RSA to test the Dual Mechanisms of Control (DMC) theoretical framework, which postulates that older adults will exhibit clear impairments in the engagement of proactive control, but relative preservation of reactive control. The project directly tests this hypothesis, employing novel theoretically-optimized variants of the work- horse color-word Stroop paradigm, combined with RSA methods, to examine the neural mechanisms associated with proactive and reactive control, using a multi-modal neuroimaging approach involving matched fMRI and EEG studies. This multi-modal approach enables a systematic and comprehensive test of the DMC framework, to test whether proactive and reactive control have distinct temporal dynamic signatures, and involve anatomically dissociable neural mechanisms within the lPFC and ACC. We further propose to enrich our understanding of the mechanisms of age-related change in cognitive control function, by capitalizing on recent advances in the ability to assess risk of preclinical Alzheimer’s Disease (AD) and AD-related neurodegeneration through the use of blood plasma-based biomarkers. Through new collaborations with Dr. Brian Gordon, Dr. Ryan Bogdan, and Dr. Suzanne Schindler, we will utilize state-of-the-art methods, including single-molecule array (Simoa) and mass spectrometry, to comprehensively assess key blood-based biomarkers related to amyloid (APOE, beta-amyloid), tau (ptau181), and neurodegeneration (NfL, GFAP), as well as anatomical MRI biomarkers (e.g., cortical thickness). We propose an Administrative Supplement to provide additional support for us to acquire, process and rigorously analyze AD-related biomarker data. This Supplement will dramatically enhance the scope, impact, and