Neural Substrates of Variability in Attention Deficit Hyperactivity Disorder (ADH

注意力缺陷多动障碍 (ADH) 变异的神经基质

• 批准号: 7851041
• 负责人: FRANCISCO XAVIER CASTELLANOS
• 金额: $ 57.65万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-10 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7851041
• 关键词: Address; Adult; Age; Anatomy; Anisotropy; Anterior; Attention deficit hyperactivity disorder; Awareness; Back; Behavioral; Biological; Biological Psychiatry; Bipolar Disorder; Brain; Brain Part; Characteristics; Child; Child Psychiatry; Childhood; Comorbidity; Complex; Data; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Drug abuse; Face; Frequencies; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Hand; Handedness; High Prevalence; Image; Impairment; Individual; Learning Disorders; Link; Maps; Matched Group; Measures; Medial; Mediator of activation protein; Methods; Modeling; Motor; Neurons; Neuropsychological Tests; Nicotine; Oppositional Defiant Disorder; Participant; Performance; Pervasive Development Disorder; Play; Prefrontal Cortex; Process; Psychopathology; Psychotic Disorders; Reaction Time; Recording of previous events; Reproduction; Research; Research Personnel; Rest; Role; Sampling; Scanning; Short-Term Memory; Socioeconomic Status; Subgroup; Symptoms; Task Performances; Testing; Therapeutic; Time; Variant; base; blood oxygen level dependent; brain behavior; cingulate cortex; cognitive control; executive function; improved; indexing; interest; myelination; neural circuit; neuroimaging; neurophysiology; neuropsychological; novel; novel strategies; outcome forecast; proband; public health relevance; relating to nervous system; response; sex; success; theories; white matter

DESCRIPTION (provided by applicant): In this revised application, we propose a novel approach to understanding the pathophysiology of Attention- Deficit/Hyperactivity Disorder (ADHD) by linking a neural circuit that has been associated with slower and more variable responses to increased intra-subject response time variability in children with ADHD. Based on extensive preliminary data in adults and children with ADHD, we hypothesize that ADHD-related abnormalities in functional connectivity (regional temporal coherence) in a circuit linking the right dorsal anterior cingulate cortex (dACC) to the retrosplenial complex (RSC; comprising precuneus and posterior cingulate cortex) which is involved in high level integration between posterior association processes and anterior executive functions, plays a key pathophysiological role in ADHD. We propose to characterize this novel locus of dysfunction by scanning 100 right-handed children so that we can analyze full imaging and neuropsychological data from at least 37 children with combined-type ADHD and 37 age-, IQ- socioeconomic status, handedness- and sex- matched healthy comparisons. We will (1) use fMRI to confirm our preliminary findings of weaker dACC/RSC functional connectivity associated with ADHD; and (2) determine whether ADHD-related increases in trial-by- trial response time variability are related to differences in the functional integrity of the dACC/RSC circuit. We will also conduct diffusion tensor imaging (DTI) studies to examine the relationship between functional and structural integrity of this key circuit, and explore key neuropsychological measures in relation to our cutting- edge measures of functional connectivity. This proposal, which combines novel methods and hypotheses with substantial preliminary data, has the potential to delineate brain-behavior relationships that will inform translational models of pathophysiology of this common and highly impairing disorder. PUBLIC HEALTH RELEVANCE: We propose to apply novel neuroimaging methods to better understand the brain mechanisms involved in Attention-Deficit/Hyperactivity Disorder (ADHD) in children. Individuals with ADHD are consistently inconsistent in their responses, and we will study a brain circuit that is associated with such inconsistency in a total of 100 children, about half of whom have ADHD and about half of whom are healthy subjects. The proposed study will allow us test a new theory about a the dysfunction of a specific brain circuit in ADHD which is believed to connect and coordinate key front and back parts of the brain. Achieving such a level of detailed information about brain functioning in ADHD would have major impact on our ability to improve methods of diagnosing ADHD and of developing new treatments.

描述（由申请人提供）：在该修订的申请中，我们提出了一种新的方法来理解注意力缺陷/多动障碍（ADHD）的病理生理学，其通过将与较慢和更可变的反应相关的神经回路与ADHD儿童中增加的受试者内反应时间变异性相关联。基于成人和儿童ADHD患者的大量初步数据，我们假设ADHD相关的功能连接异常在连接右背前扣带皮层（dACC）和压后复合体的回路中，（RSC;包括楔前叶和后扣带皮层），其参与后联合过程和前执行功能之间的高水平整合，在多动症中起着关键的病理生理作用。我们建议通过扫描100名右利手儿童来描述这种新的功能障碍位点，以便我们可以分析来自至少37名患有混合型ADHD的儿童和37名年龄，智商，社会经济地位，利手和性别匹配的健康对照的完整成像和神经心理学数据。我们将（1）使用fMRI来证实我们的初步发现，即与ADHD相关的dACC/RSC功能连接较弱;（2）确定ADHD相关的试验-试验反应时间变异性增加是否与dACC/RSC回路功能完整性的差异有关。我们还将进行扩散张量成像（DTI）研究，以检查这一关键回路的功能和结构完整性之间的关系，并探索与我们的功能连接性尖端测量相关的关键神经心理学测量。这个建议，结合了新的方法和假设与大量的初步数据，有可能描绘大脑行为的关系，将告知翻译模型的病理生理学这种常见的和高度损害的疾病。公共卫生关系：我们建议应用新的神经影像学方法，以更好地了解儿童注意力缺陷多动障碍（ADHD）的大脑机制。ADHD患者的反应总是不一致，我们将在总共100名儿童中研究与这种不一致相关的大脑回路，其中大约一半患有ADHD，大约一半是健康受试者。这项拟议中的研究将使我们能够测试一种新的理论，即ADHD中特定大脑回路的功能障碍，这种功能障碍被认为是连接和协调大脑的关键前部和后部。获得关于ADHD大脑功能的详细信息将对我们改善ADHD诊断方法和开发新治疗方法的能力产生重大影响。

项目成果

Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder.

• DOI: 10.1016/j.nicl.2015.10.017
• 发表时间: 2016
• 期刊: NeuroImage. Clinical
• 作者: Blackmon K;Ben-Avi E;Wang X;Pardoe HR;Di Martino A;Halgren E;Devinsky O;Thesen T;Kuzniecky R
• 通讯作者: Kuzniecky R

Response-time variability is related to parent ratings of inattention, hyperactivity, and executive function.

• DOI: 10.1177/1087054709356379
• 发表时间: 2011-10
• 期刊: Journal of attention disorders
• 影响因子: 3
• 作者: Gómez-Guerrero L;Martín CD;Mairena MA;Di Martino A;Wang J;Mendelsohn AL;Dreyer BP;Isquith PK;Gioia G;Petkova E;Castellanos FX
• 通讯作者: Castellanos FX

Dimensional brain-behavior relationships in children with attention-deficit/hyperactivity disorder.

• DOI: 10.1016/j.biopsych.2011.08.013
• 发表时间: 2012-03-01
• 期刊: BIOLOGICAL PSYCHIATRY
• 影响因子: 10.6
• 作者: Chabernaud, Camille;Mennes, Maarten;Kelly, Clare;Nooner, Kate;Di Martino, Adriana;Castellanos, F. Xavier;Milham, Michael P.
• 通讯作者: Milham, Michael P.

Is Increased Response Time Variability Related to Deficient Emotional Self-Regulation in Children With ADHD?

• DOI: 10.1177/1087054718788950
• 发表时间: 2020-05-01
• 期刊: JOURNAL OF ATTENTION DISORDERS
• 影响因子: 3
• 作者: Elmaghrabi, Shereen;Nahmias, Maria Julia;Castellanos, Francisco X.
• 通讯作者: Castellanos, Francisco X.

Reliable intrinsic connectivity networks: test-retest evaluation using ICA and dual regression approach.

• DOI: 10.1016/j.neuroimage.2009.10.080
• 发表时间: 2010-02-01
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Zuo XN;Kelly C;Adelstein JS;Klein DF;Castellanos FX;Milham MP
• 通讯作者: Milham MP