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

衰老对主动和反应性认知控制神经编码的影响：行政补充

基本信息

批准号：
10715441
负责人：
TODD S BRAVER
金额：
$ 38.8万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10715441
关键词：
Administrative Supplement Adopted Adoption Age-associated memory impairment Aging Alzheimer associated neurodegeneration Alzheimer&apos s Disease Alzheimer’s disease biomarker Amyloid Amyloid beta-Protein Anatomy Anterior Award Behavioral Biological Markers Blood Blood specimen Brain Code Cognitive aging Collaborations Color Communities Consensus Data Data Collection Development Diagnostic Dissociation Elderly Emotions Ensure Exhibits Experimental Designs Funding Future Glial Fibrillary Acidic Protein Goals Grant Human Resources Impaired cognition Impairment Intervention Laboratories Lateral Life Link Literature Mass Spectrum Analysis Methodology Methods Midbrain structure Mission Modality Nerve Degeneration Neurobiology Participant Pathologic Pathology Pattern Plasma Prefrontal Cortex Process Research Research Design Research Personnel Research Project Grants Risk Assessment Sampling Science Specificity Stimulus Subgroup Techniques Testing Thick Thinking Universities Variant Washington Well in self Work age effect age related blood-based biomarker brain behavior cingulate cortex cognitive control cognitive function cognitive neuroscience cost effective dopamine system experience falls functional magnetic resonance imaging/electroencephalography healthy aging indexing innovation magnetic resonance imaging biomarker medical schools multimodal neuroimaging multimodality neural neuroimaging marker neuromechanism novel pilot test pre-clinical preservation prospective psychologic single molecule success tau Proteins temporal measurement

项目摘要

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

项目概要该提案探讨了公认的下降背后的神经和心理机制。健康老年人所经历的认知控制功能在认知方面达成了明确的共识。衰老的神经科学认为，与年龄相关的认知控制能力下降反映了发生的神经生物学变化在中脑多巴胺系统的功能中，与位于外侧前额叶的目标相互作用皮层（lPFC）和前扣带皮层（ACC）当前的提议采用了创新的实验。通过利用代表性相似性分析（RSA）的方法来解决这个问题具体来说，我们利用认知控制的神经编码及其如何随着年龄的增长而变化。 RSA 测试双重控制机制 (DMC) 理论框架，该框架假设老年人主动控制的参与将表现出明显的损害，但反应性控制的相对保留该项目直接测试了这一假设，采用了新颖的理论优化变体。马色词斯特鲁普范式，结合RSA方法，检验神经机制与主动和反应控制相关，使用多模式神经影像方法，涉及匹配这种多模态方法可以对 DMC 进行系统且全面的测试。框架，测试主动和被动控制是否具有不同的时间动态特征，并涉及我们进一步建议丰富我们的 LPFC 和 ACC 内的解剖学分离神经机制。通过利用最近的研究，了解认知控制功能中与年龄相关的变化的机制评估临床前阿尔茨海默病 (AD) 和 AD 相关疾病风险的能力取得进展通过使用基于血浆的生物标记物来治疗神经退行性疾病。 Brian Gordon、Ryan Bogdan 博士和 Suzanne Schindler 博士，我们将利用最先进的方法，包括单分子阵列 (Simoa) 和质谱分析，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蛋白（ptau181）和神经变性（NfL、GFAP）相关，以及我们提出了一份行政补充文件来提供解剖 MRI 生物标志物（例如皮质厚度）。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。将极大地扩大范围、影响和