Characterization of executive function dimensions across pediatric psychiatric disorders

儿科精神疾病执行功能维度的表征

基本信息

批准号：
9471432
负责人：
LAUREN KENWORTHY
金额：
$ 38.55万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-19 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9471432
关键词：
13 year old Accounting Address Amygdaloid structure Anxiety Disorders Arousal Attention deficit hyperactivity disorder Back Behavior Behavior Therapy Behavioral Brain Categories Child Child Behavior Checklist Childhood Classification Clinic Clinical Communities Comorbidity Corpus striatum structure Data Detection Diagnosis Diagnostic Dimensions Disease Disruptive Behavior Disorder Dorsal Emotional Equipment and supply inventories Executive Dysfunction Factor Analysis Failure Functional Magnetic Resonance Imaging Generations Gilles de la Tourette syndrome Goals Heterogeneity Hyperactive behavior Impairment Impulsive Behavior Impulsivity Intervention Lateral Learning Disabilities Life Link Machine Learning Measures Mediating Medical Medical center Mental disorders Methods Mood Disorders Nature Neurobiology Neuropsychology Outcome Outpatients Parents Parietal Pathway interactions Patient Self-Report Pattern Phenotype Population Process Property Psychiatric Diagnosis Quality of life Reporting Research Domain Criteria Rest Risk Services Short-Term Memory Symptoms System Testing Thinking Tic disorder Training Work associated symptom autism spectrum disorder base clinical practice clinically significant cognitive control cognitive system cohort comparison group dimensional analysis disease classification emotion regulation executive function falls flexibility graph theory inattention neural circuit novel personalized approach recruit response skills social success teacher treatment effect

项目摘要

PROJECT SUMMARY The proposal responds to RFA-MH-16-510 by focusing on the domain of “Cognitive Systems” and constructs “cognitive control” and “working memory” and integrating units of analysis “brain circuit” and “behavior”. These constructs are subsumed under executive function (EF), the ability to voluntarily constrain thoughts and actions in the service of goals. Among pediatric psychiatric categories, EF deficits define Attention Deficit Hyperactivity Disorder (ADHD) and are comorbid with a variety disorders, including Autism Spectrum Disorders, disruptive behavior disorders, mood and anxiety disorders, Tourette's/tics, and learning disabilities. Across these disorders, EF deficits limit adaptive functioning and success of behavioral intervention. Ameliorating EF deficits is a challenge, however, because current EF nosology falls short of capturing heterogeneity within and across disorders. The primary challenge then is identifying the dimensions of EF that capture the specific nature of impairment across disorders. Most past approaches utilize dimension- reducing methods that are sensitive to shared variance, but exclude unique variance. Here, we address this challenge through novel data-driven generation of behavioral profile-based EF dimensions derived from graph theory community-detection (following [1, 2]), applied to common clinical parent-report measures (ADHD Rating scale, inattention, hyperactivity/impulsivity, 8 Behavior Rating Inventory of Executive Function subdomains, Child Behavior Checklist internalizing, and externalizing). Community-detection applied to N=322 (8-13 yrs; IQ>70; no “medical” diagnosis) presenting at Children's National Medical Center neuropsychology clinics identified three EF profiles distinguished by deficits and relative strengths: 1) poor working memory; good flexibility and inhibition; 2) poor inhibition; good working memory; 3) poor flexibility and emotion regulation; good working memory. We will recruit from this growing cohort to examine: Aim 1 – seek replication by testing a new larger cohort with support vector machine classification trained on preliminary data. Aim 2 - characterize functional networks distinguishing the 3 profiles, by group comparison and dimensional analysis. Task-based functional connectivity will test hypothesis about specific circuits distinguishing the novel EF dimensions using fMRI during: 1) N-back working memory; 2) Response inhibition; and 3) Adaptive socio-emotional cognitive control. Task-free resting-state fMRI will test hypothesis about large-scale network interaction differences between EF dimensions. Aim 3 - test the hypothesis that the novel EF dimensions are associated with specific domains of adaptive function, mediated by specific functional networks. Results will: 1) provide neurobiologically validated EF dimensions for re- conceptualizing pediatric psychiatric nosology, and 2) identify treatment targets and increase precision in measuring treatment effects – i.e., who should receive what treatment and how to best measure response and outcome, both of which are essential to the success of a personalized approach to clinical practice.

项目摘要提案对RFA-MH-16-510的响应通过着重于“认知系统”的领域并构建 “认知控制”和“工作记忆”以及整合分析单位“脑电路”和“行为”。这些构造被纳入执行功能（EF），即自愿限制思想和行动的能力为目标服务。在小儿精神科类别中，EF定义注意力缺陷多动症疾病（ADHD），并且合并有多种疾病，包括自闭症谱系障碍，破坏性行为障碍，情绪和焦虑症，Tourette/TICS和学习障碍。遍及这些 EF疾病定义了限制自适应功能和行为干预的成功。改善EF 但是，缺陷是一个挑战，因为当前的EF病态缺乏捕获异质性内外疾病。然后，主要的挑战是确定EF的维度捕获跨疾病的损害的具体性质。过去的大多数方法都利用维度 - 还原对共享差异敏感但排除唯一方差的方法。在这里，我们解决通过新颖的数据驱动的基于行为概况的EF维度来挑战的挑战图理论社区检测（以下[1，2]），适用于常见的临床父母报告措施（ADHD 评级量表，注意力不集中，多动症/冲动性，8行政职能库存库存子域，儿童行为清单内部化和外部化）。社区检测应用于n = 322 （8-13岁； IQ> 70;无“医学”诊断）在儿童国家医学中心神经心理学诊所确定了三个通过区分的EF轮廓定义和相对强度：1）工作记忆不佳；良好的灵活性和抑制作用； 2）抑制不良；良好的工作记忆； 3）灵活性和情感不佳规定;良好的工作记忆。我们将从这个不断增长的队列中招募考试：目标1 - 寻求通过测试新的较大队列的复制初步数据。 AIM 2-表征通过组区分3个配置文件的功能网络比较和维度分析。基于任务的功能连接将测试有关特定的假设在以下过程中使用fMRI区分新颖的EF维度的电路：1）n背部工作记忆； 2）响应抑制; 3）自适应社会情感控制。无任务休息状态fMRI将检验假设关于EF维度之间的大规模网络交互差异。目标3-检验以下假设新型的EF维度与自适应功能的特定域相关联，由特定的功能网络。结果将：1）提供经过神经生物学验证的EF维度以进行重新概念化儿科精神病学，以及2）确定治疗目标并提高精度测量治疗效果 - 即谁应该接受什么治疗以及如何最佳衡量响应和结果，这两种结果对于成功的临床实践方法的成功至关重要。