Network Mechanisms of Flexible Cognitive Control

灵活认知控制的网络机制

• 批准号: 8773729
• 负责人: Michael William Cole
• 金额: $ 24.9万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-03 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8773729
• 关键词: Adaptive Behaviors; Affect; Award; Behavior; Behavioral; Biological Neural Networks; Brain; Brain region; Cellular Phone; 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; abstracting; 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

Project Summary/Abstract 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 of 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, training 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 link 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 trial) 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 phone (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.

项目摘要/摘要 这个独立之路奖(K99/R00)申请的目标是获得认知方面的培训 灵活认知控制的神经科学和专家研究人员的脑网络分析 独立性，该培训将用于启动一个调查网络机制的实验室 灵活的控制。灵活的控制-支持日常重要的适应性、目标导向行为的能力 生活--受到各种精神疾病的影响，显著降低了生活质量。关键的是，这些机制 在认知和神经层面上，人们对潜在的灵活控制仍然知之甚少。一大堆 证据表明，在不同的情况下，灵活的控制是由一组额顶叶 大脑区域有时被称为认知控制网络(CCN)。我们最近发现CCN 人类大脑中具有最高全球大脑连接性(GBC)的区域之一，更重要的是， 外侧前额叶CCN区域的GBC强烈预测流体推理--表明灵活的控制与 特定大脑区域的全局连接特性。基于这些发现，我们假设 集线器假设：某些CCN区域能够利用其广泛的连通性灵活地重新配置 根据任务当前活跃的连接(具有与任务相关的感觉、语义和运动区) 要求。我们将研究这样一种假设，即柔性中枢是支撑柔性的关键神经机制 控制通过确定神经网络和认知属性之间的关系而灵活 集线器和灵活的控制。在指导(K99)阶段，我将接受图论博士的培训。 Steve Petersen(共同导师)、Olaf Sporns博士(合作者)和Deanna Bch博士(合作者)使 开发更精确的量化网络属性指标，可以灵活地识别和定义 人脑中的中枢。此外，托德·布雷弗博士(导师)对个人差异方法的培训 而兰德尔·恩格尔博士(合作者)将使更多数量上精确的认知发展成为可能 灵活控制的措施。在独立(R00)阶段，我们将在此研究和 培训以确定动态(跨任务)灵活的集线器连接变化与稳定网络的关系 性能和灵活的控制能力。这种对灵活集线器和 灵活控制将使您能够更全面地了解 各种精神疾病。培训将在圣路易斯的华盛顿大学进行，该校拥有广泛的 智力和设备资源，用于对涉及个人的执行职能进行研究 差异和功能连接磁共振成像(FcMRI)。布雷弗博士是一位世界专家 认知控制研究，有丰富的使用个体差异方法论的经验 功能核磁共振，这使他成为拟议的培训计划的优秀导师。彼得森博士是一个世界 在开发图论fcMRI方法并将其应用于认知控制研究方面的专家，使他 建议的培训计划的优秀合作导师。重要的是，一些久负盛名的合作者将 我还补充了我在K99阶段和过渡到独立R00期间的培训和评估 相位。我一直致力于研究执行功能的认知神经科学，从我 他是加州大学伯克利分校马克·德斯波西托实验室的本科生。后来，我上了研究生。 沃尔特·施奈德在匹兹堡大学的实验室工作，并获得了神经科学博士学位。我的 研究生研究导致了基于创新研究方法的多份第一作者出版物 由于我强烈的独立研究兴趣。具体地说，这些兴趣使我主要关注两条线 研究方向：快速指导式任务学习(RITL)和GBC。第一，RITL，调查执行职能 潜在的灵活、适应性的人类行为(即灵活的认知控制)。这很重要，也很及时。 研究仍然是一个谜，健康的人如何能够迅速(即，在一次试验中)学习 几乎有无限种可能的任务(以及这种能力如何在精神疾病中受损)。为 例如，此能力在个人第一次使用手机时使用(以适应来自 固定电话)，或任何新技术。第二条线的研究，GBC，专注于描述 大脑中连接最紧密的区域。我在布雷弗博士的实验室做博士后的时间非常长 卓有成效，因为我已经学习了新的先进的fMRI方法，如多变量模式分析(MVPA)， 开发了一种新的RITL认知范式，并发表了一篇研究精神分裂症患者GBC缺陷的论文， 在其他成就中。关键是，拟议的研究计划将结合起来--并从协同中受益 在RITL和GBC之间进行研究，为组建自己的独立实验室做准备。我 计划主要在这两个研究方向的交汇处发展我的实验室：调查方法 其中，大脑网络连接指定了灵活认知控制背后的动态。培训 这份K99/R00提案中概述的研究和研究是我职业发展计划的重要组成部分 转变为一名成功的独立研究人员。