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）：该独立之路奖（K99/R00）申请的目标是从专家研究人员那里获得灵活认知控制和脑网络分析的认知神经科学培训，为独立做准备，该培训将用于启动一个实验室，研究灵活控制的网络机制。灵活控制——一种支持日常生活中重要的适应性、目标导向行为的能力——会受到各种精神疾病的影响，显着降低生活质量。至关重要的是，灵活控制背后的机制在认知和神经层面仍然知之甚少。大量证据表明，灵活的控制是由一组额顶叶脑区域（有时称为认知控制网络（CCN））在各种情况下实现的。我们最近发现 CCN 区域具有人脑中最高的全局大脑连接性 (GBC)，更重要的是，外侧前额叶 CCN 区域的 GBC 强烈预测流体推理 - 这表明灵活 控制与特定大脑区域的全局连接特性有关。基于这些发现，我们提出灵活枢纽假设：一些 CCN 区域能够根据任务需求，利用其广泛的连接来灵活地重新配置当前活动的连接（与任务相关的感觉、语义和运动区域）。我们将通过确定灵活中枢和灵活控制之间关系背后的神经网络和认知特性来研究灵活中枢是灵活控制背后的关键神经机制的假设。在指导（K99）阶段，我将接受 Steve Petersen 博士（共同导师）、Olaf Sporns 博士（合作者）和 Deanna Barch 博士（合作者）的图论培训，以开发更定量精确的网络属性指标，这些指标可以识别和定义人脑中的灵活中枢。此外，Todd Braver 博士（导师）和 Randall Engle 博士（合作者）对个体差异方法的培训将有助于开发更加定量精确的灵活控制认知测量方法。在独立（R00）阶段，我们将在此研究和培训的基础上确定动态（跨任务）灵活的集线器连接变化如何与稳定的网络属性和灵活的控制能力相关。这种对灵活中枢和灵活控制之间联系的严格表征将使人们能够更全面地了解各种精神疾病中存在的灵活控制障碍。将进行培训 圣路易斯华盛顿大学拥有广泛的智力和设备资源，可用于开展涉及个体差异和功能连接磁共振成像（fcMRI）的执行功能研究。 Braver 博士是认知控制研究方面的世界专家，在使用个体差异方法和功能 MRI 方面拥有丰富的经验，这使他成为拟议培训计划的优秀导师。 Petersen 博士是开发图论 fcMRI 方法并将其应用于认知控制研究的世界专家，这使他成为拟议培训计划的优秀联合导师。重要的是，几位成熟的合作者也将补充我在 K99 阶段和过渡到独立 R00 阶段期间的培训和评估。自从我在加州大学伯克利分校 Mark D'Esposito 实验室读本科以来，我就一直对研究执行功能的认知神经科学感兴趣。随后，我在匹兹堡大学沃尔特·施耐德实验室读研究生，并获得了博士学位。在神经科学中。我的研究生研究基于我强烈的独立研究兴趣驱动的创新研究方法，发表了多篇第一作者出版物。具体来说，这些兴趣使我主要关注两条研究方向：快速指导任务学习 (RITL) 和 GBC。第一个是 RITL，研究灵活、适应性人类行为（即灵活的认知控制）背后的执行功能。这是一项重要且及时的研究，因为健康个体如何能够快速（即在一次三分钟内）学习几乎无限多种可能的任务（以及这种能力如何在精神疾病中受到损害）仍然是一个谜。例如，当个人第一次使用手机（为了适应与“固定电话”电话的差异）或任何新技术时，就会使用这种能力。第二条研究线 GBC 的重点是描述大脑中连接最紧密的区域。我在 Braver 博士实验室担任博士后期间非常富有成效，因为我学习了新的先进功能磁共振成像方法，例如多元模式分析 (MVPA)，开发了新的 RITL 认知范式，并发表了一篇研究精神分裂症中 GBC 缺陷的论文，以及其他成就。至关重要的是，拟议的研究计划将结合 RITL 和 GBC 的研究路线并受益于它们之间的协同作用，为组建我自己的独立实验室做准备。我计划主要在这两条研究路线的交汇处发展我的实验室：研究大脑网络连接指定灵活认知控制背后的动态的方式。当我过渡到成为一名成功的独立研究员时，本 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。 公共健康相关性：灵活的认知控制支持日常生活中重要的适应性行为，并且明显受到各种精神疾病（例如精神分裂症、抑郁症）的影响，但人们对这种能力背后的机制知之甚少。我们将使用新颖的行为和大脑网络分析来提高对人脑如何实施灵活认知控制的基本理解，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。