Network Mechanisms of Flexible Cognitive Control

灵活认知控制的网络机制

• 批准号: 8280752
• 负责人: Michael William Cole
• 金额: $ 8.27万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8280752
• 关键词: Adaptive Behaviors; Affect; Award; Behavior; Behavioral; Biological Neural Networks; Brain; Brain region; Cells; Cognitive; Data Set; Development; Development Plans; Doctor of Philosophy; Educational Status; Equipment; Evaluation; Exhibits; Factor Analysis; Functional Magnetic Resonance Imaging; Goals; Graph; Human; Impairment; Individual; Individual Differences; Laboratories; Lateral; Learning; Life; Link; Liquid substance; Magnetic Resonance Imaging; Measures; Mental Depression; Mental disorders; Mentors; Methodology; Methods; Motor; Neurosciences; Paper; Parietal; Pathway Analysis; Pathway interactions; Pattern; Phase; Phase Transition; Postdoctoral Fellow; Prefrontal Cortex; Preparation; Procedures; Property; Proxy; Publications; Publishing; Quality of life; Research; Research Personnel; Research Training; Resources; Reversal Learning; Schizophrenia; Schools; Semantics; Sensory; Specific qualifier value; Statistical Models; Telephone; Testing; Time; Training; Universities; Washington; base; career development; cognitive control; cognitive neuroscience; executive function; experience; flexibility; imaging modality; improved; indexing; innovation; interest; neuromechanism; new technology; novel; relating to nervous system; theories

DESCRIPTION (provided by applicant): The goal of this Pathway to Independence Award (K99/R00) application is to obtain training in the cognitive neuroscience of flexible cognitive control and brain network analysis from expert researchers in preparation for independence, where this training will be used to start a laboratory that investigates the network mechanisms of flexible control. Flexible control - a capacity supporting adaptive, goal-directed behavior important in daily life - is affected in a variety of mental illnesses, markedly reducing quality o life. Critically, the mechanisms underlying flexible control remain poorly understood at both cognitive and neural levels. A large body of evidence suggests that flexible control is implemented across a variety of situations by a set of fronto-parietal brain regions sometimes referred to as the cognitive control network (CCN). We recently found that CCN regions have among the highest global brain connectivity (GBC) in the human brain and, more importantly, that GBC in a lateral prefrontal CCN region strongly predicts fluid reasoning - suggesting flexible control is linked to the global connectivity properties of specific brain regions. Based on these findings, we postulate the flexible hub hypothesis: that some CCN regions are able to use their extensive connectivity to flexibly reconfigure currently active connections (with task-relevant sensory, semantic, and motor regions) according to task demands. We will investigate the hypothesis that flexible hubs are a key neural mechanism underlying flexible control by determining the neural network and cognitive properties underlying the relationship between flexible hubs and flexible control. During the mentored (K99) phase I will receive training in graph theory from Dr. Steve Petersen (co-mentor), Dr. Olaf Sporns (collaborator), and Dr. Deanna Barch (collaborator) to enable the development of more quantitatively precise network property indicators that can identify and define flexible hubs in the human brain. Further, trainin in individual differences approaches from Dr. Todd Braver (mentor) and Dr. Randall Engle (collaborator) will enable the development of more quantitatively precise cognitive measures of flexible control. During the independent (R00) phase we will then build upon this research and training to determine how dynamic (across-task) flexible hub connectivity changes are related to stable network properties and flexible control abilities. This rigorous characterization of the lin between flexible hubs and flexible control will enable a more comprehensive understanding of the flexible control impairments present in a variety of mental illnesses. Training will take place at Washington University in St. Louis, which has extensive intellectual and equipment resources for conducting studies of executive functions involving individual differences and functional connectivity magnetic resonance imaging (fcMRI). Dr. Braver is a world expert in cognitive control research and has extensive experience using individual differences methodology with functional MRI, which makes him an excellent mentor for the proposed training plan. Dr. Petersen is a world expert in developing graph theory fcMRI methods and applying them to cognitive control research, makes him an excellent co-mentor for the proposed training plan. Importantly, several well-established collaborators will also supplement my training and evaluation during the K99 phase and the transition into the independent R00 phase. I have pursued my interest in researching the cognitive neuroscience of executive functions since I was an undergraduate in Mark D'Esposito's laboratory at UC Berkeley. I subsequently went to graduate school in Walter Schneider's laboratory at the University of Pittsburgh and received a Ph.D. in Neuroscience. My graduate research led to multiple first-authored publications based on innovative research approaches driven by my strong independent research interests. Specifically, these interests led me to focus primarily on two lines of research: rapid instructed task learning (RITL) and GBC. The first, RITL, investigates the executive functions underlying flexible, adaptive human behavior (i.e., flexible cognitive control). This is important and timely research as it remains a mystery how healthy individuals are able to rapidly (i.e., in a single tril) learn a virtually infinite variety of possible tasks (and how this ability can become impaired in mental illnesses). For instance, this ability is used the first time an individual uses a cell phon (in order to adapt to differences from 'landline' phones), or any new technology. The second line of research, GBC, is focused on characterizing the brain's most connected regions. My time as a postdoctoral fellow in Dr. Braver's lab has been highly productive, as I have learned new advanced fMRI methods such as multivariate pattern analysis (MVPA), developed a new RITL cognitive paradigm, and published a paper investigating GBC deficits in schizophrenia, among other accomplishment. Critically, the proposed research plan will combine - and benefit from synergy between - the RITL and GBC lines of research in preparation for forming my own independent laboratory. I plan to develop my laboratory primarily at the confluence of these two lines of research: investigating the ways in which brain network connectivity specifies the dynamics underlying flexible cognitive control. The training and research outlined in this K99/R00 proposal are essential components of my career development plans as I transition to becoming a successful independent researcher. PUBLIC HEALTH RELEVANCE: Flexible cognitive control supports adaptive behavior important in daily life and is clearly affected in a variety of mental illnesses (e.g., schizophrena, depression), yet the mechanisms underlying this ability are poorly understood. We will use novel behavioral and brain network analyses to improve basic understanding of how flexible cognitive control is implemented in the human brain, providing a more comprehensive understanding of the flexible cognitive control impairments present in a variety of mental illnesses.

描述（由申请人提供）：该途径获得独立奖的目的（K99/R00）的应用是要获得专家研究人员的灵活认知控制和大脑网络分析的认知神经科学的培训，以准备独立性，在此培训中，该培训将用于启动一个实验室，以研究灵活控制网络机制。灵活的控制 - 支持适应性，目标指导行为在日常生活中很重要的能力 - 在各种精神疾病中都受到影响，从而显着降低了质量的O生活。至关重要的是，在认知水平和神经水平上，柔性控制的机制仍然很少了解。大量证据表明，在各种情况下，通过一组额顶大脑区域（有时称为认知控制网络（CCN））实现了灵活的控制。我们最近发现，CCN区域在人脑中具有最高的全球脑连接性（GBC），更重要的是，横向前额叶CCN区域中的GBC强烈预测流体推理 - 表明灵活 控制与特定大脑区域的全球连通性特性有关。基于这些发现，我们假设灵活的集线器假设：某些CCN区域能够根据任务要求灵活地重新配置当前有效连接（具有与任务相关的感觉，语义和运动区域）。我们将通过确定灵活控制和柔性控制之间关系的基础的神经网络和认知特性来调查柔性枢纽是柔性控制的关键神经机制。在指导的（K99）期间，第一阶段将获得史蒂夫·彼得森（Steve Petersen）博士（同事），奥拉夫·斯波恩斯（Olaf Sporns）（合作者）和迪安娜·巴奇（Deanna Barch）博士（合作者）的培训，以促进可以识别和定义人脑中灵活枢纽的更定量精确的网络属性指标。此外，Trainin采用了Todd Braver博士（Mentor）和Randall Engle博士（合作者）的个体差异方法，将使更定量的灵活控制的认知度量更为精确。然后，在独立（R00）阶段，我们将基于此研究和培训，以确定动态（跨任务）灵活的集线器连接性变化与稳定的网络属性和灵活的控制能力有关。灵活枢纽和灵活控制之间的LIN的严格表征将使人们能够对各种精神疾病中存在的灵活控制障碍有更全面的了解。培训将进行 在圣路易斯的华盛顿大学，该大学拥有广泛的知识和设备资源，用于对涉及个体差异和功能连通性磁共振成像（FCMRI）的执行功能进行研究。 Braver博士是认知控制研究的世界专家，并使用功能性MRI的个体差异方法具有丰富的经验，这使他成为了拟议的培训计划的出色指导者。 Petersen博士是开发图理论FCMRI方法的世界专家，并将其应用于认知控制研究，使他成为拟议培训计划的出色院长。重要的是，几个成熟的合作者还将补充我在K99阶段的培训和评估，并过渡到独立R00阶段。自从我是加州大学伯克利分校的马克·埃斯波西托（Mark D'Esposito）实验室的本科生以来，我一直对研究执行功能的认知神经科学的兴趣。随后，我去了匹兹堡大学沃尔特·施耐德（Walter Schneider）实验室的研究生院，并获得了博士学位。在神经科学中。我的研究生研究导致了基于我强大的独立研究兴趣驱动的创新研究方法，从而导致了多个创作的出版物。具体而言，这些兴趣使我主要关注两项研究：快速指导任务学习（RITL）和GBC。首先，RITL调查了行政功能的灵活性，适应性人类行为（即灵活的认知控制）。这是重要及时的研究，因为它仍然是一个谜，这仍然是一个谜，那么健康的人如何能够迅速（即单一三核）学习几乎无限的可能任务（以及这种能力如何在精神疾病中受到损害）。例如，首次使用单个窗口电话（以适应“座机”手机的差异）或任何新技术时使用此功能。第二条研究GBC的重点是表征大脑最连接的区域。我在Braver博士实验室中担任博士后研究员的时间非常有生产力，因为我已经学到了新的先进功能磁共振成像方法，例如多元模式分析（MVPA），开发了一种新的RITL认知范式，并发表了一篇论文研究了精神分裂症的GBC缺陷，以及其他成就。至关重要的是，拟议的研究计划将结合起来并受益于RITL和GBC研究线之间的协同作用，以准备形成我自己的独立实验室。我计划主要在这两条研究的汇合处开发我的实验室：研究大脑网络连通性指定灵活认知控制的动态的方式。当我过渡成为成功的独立研究员时，这项K99/R00提案中概述的培训和研究是我职业发展计划的重要组成部分。 公共卫生相关性：灵活的认知控制支持在日常生活中重要的适应性行为，并且在各种精神疾病（例如精神分裂症，抑郁症）中显然受到影响，但是对这种能力的机制却很少了解。我们将使用新颖的行为和大脑网络分析来提高人们对人脑中灵活认知控制的基本了解，从而更全面地了解各种精神疾病中存在的灵活认知控制障碍。