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 该途径获得独立奖的目标（K99/R00）申请是获得认知培训 专家研究人员的灵活认知控制和大脑网络分析的神经科学为准备 独立性，该培训将用于启动研究网络机制的实验室 灵活控制。灵活控制 - 能力支持适应性，目标指导行为在每日重要 生活 - 受到各种精神疾病的影响，显着降低了生活质量。至关重要的是机制 在认知和神经水平上，潜在的柔性控制仍然很少理解。一大堆 有证据表明，通过一组额叶 - 额叶在各种情况下实现了灵活的控制 大脑区域有时称为认知控制网络（CCN）。我们最近发现CCN 地区在人脑中拥有最高的全球大脑连通性（GBC），更重要的是 GBC在侧面前额叶CCN区域中强烈预测流体推理 - 表明柔性控制与 特定大脑区域的全球连通性特性。根据这些发现，我们假设灵活 集线器假设：某些CCN区域能够使用其广泛的连接来灵活地重新配置 根据任务，当前有效的连接（具有任务相关的感觉，语义和运动区域） 需求。我们将调查柔性枢纽是灵活的关键神经机制的假设 通过确定灵活关系之间关系的神经网络和认知特性来控制 轮毂和灵活的控制。在指导的（K99）期间，我将从博士那里获得图形理论的培训。 史蒂夫·彼得森（Co-Contor），奥拉夫·斯波恩斯（Olaf Sporns）博士（合作者）和迪安娜·巴奇（Deanna Barch）博士（合作者）启用 开发更定量的精确网络属性指标，这些指标可以识别并定义灵活性 人脑中的集线器。此外，托德·布拉弗（Todd Braver）博士（导师）的个体差异方法培训 兰德尔·恩格尔（Randall Engle 灵活控制的度量。在独立（R00）阶段，我们将在这项研究的基础上进行，并 训练以确定动态（跨任务）灵活集线器连接性的变化与稳定网络有关 属性和灵活的控制能力。灵活枢纽和 灵活的控制将使对A中存在的灵活控制障碍有更全面的了解 各种精神疾病。培训将在圣路易斯的华盛顿大学进行，该大学有广泛的 智力和设备资源用于进行涉及个人的行政职能的研究 差异和功能连通性磁共振成像（FCMRI）。 Braver博士是世界专家 认知控制研究，并使用个体差异方法具有丰富的经验 功能性MRI，这使他成为拟议培训计划的出色指导者。彼得森博士是一个世界 开发图理论FCMRI方法并将其应用于认知控制研究的专家，使他 拟议的培训计划的出色院长。重要的是，几位公认的合作者将 还可以补充我在K99阶段的培训和评估以及向独立R00的过渡 阶段。我一直在研究研究执行功能的认知神经科学的兴趣，因为我 位于加州大学伯克利分校的马克·埃斯波斯托（Mark D'Esposito）实验室的本科生。随后我去了 匹兹堡大学的沃尔特·施耐德（Walter Schneider）的实验室，并获得了博士学位。在神经科学中。我的 研究生研究导致基于创新研究方法驱动的多个第一著名的出版物 由我强大的独立研究兴趣。具体来说，这些兴趣使我主要关注两行 研究：快速指导任务学习（RITL）和GBC。首先，RITL调查了执行职能 潜在的灵活，适应性的人类行为（即灵活的认知控制）。这很重要且及时 研究仍然是一个谜，这仍然是一个谜 实际上，无限的任务多种多样（以及这种能力如何在精神疾病中受到损害）。为了 实例，第一次使用手机时使用此功能（以适应与 “座机”电话）或任何新技术。第二条研究的GBC专注于表征 大脑最连接的区域。我在Braver博士实验室的博士后研究员的时间很高 富有成效的，因为我已经学到了新的高级fMRI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， 除其他成就。至关重要的是，拟议的研究计划将结合起来 - 并从协同作用中受益 之间 - 在形成我自己的独立实验室的准备工作中，RITL和GBC研究线。我 计划主要在这两条研究的汇合处开发我的实验室：调查方式 其中大脑网络连接指定了灵活认知控制的基础动力学。培训 这本K99/R00提案中概述的研究是我职业发展计划的重要组成部分 过渡到成为一名成功的独立研究人员。