Neuroimaging of Top-Down Control and Bottom-Up Processes in Childhood ASD

儿童自闭症谱系障碍自上而下控制和自下而上过程的神经影像学

基本信息

批准号：
8447542
负责人：
Chandan J Vaidya
金额：
$ 37.18万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8447542
关键词：
12 year old Address Affect Age Amygdaloid structure Anger Anterior Anxiety Anxiety Disorders Attention Behavior Behavior Therapy Behavioral Brain Brain imaging Build-it Child Childhood Clinical Cognition Cognitive deficits Collaborations Comorbidity Conflict (Psychology)Corpus striatum structure Data Development Diffusion Magnetic Resonance Imaging Dimensions Disease Dorsal Emotional Emotions Equilibrium Face Functional Magnetic Resonance Imaging Functional disorder Gender Goals Heterogeneity Impulsivity Individual Individual Differences Knowledge Mediating Methods Modeling Neuroanatomy Parietal Pharmacological Treatment Prefrontal Cortex Process Psychopathology Research Resolution Rest Scanning Services Severities Stimulus Symptoms Testing Variant autism spectrum disorder cognitive function cognitive neuroscience executive function information processing neuroimaging novel novel strategies operation response social theories trait white matter

项目摘要

ABSTRACT Autism Spectrum Disorder (ASD) is characterized by pervasive socio-emotional and cognitive deficits even in children with high intellectual function. Its neuropathophysiology involves executive dysfunction mediated by prefrontal cortex but is not well-understood, due to high phenotypic heterogeneity and comorbidity with attention and anxiety disorders and a lack of resolution in affected component processes of executive function. We postulate that symptom expression varies among ASD children due to the influence of traits that characterize comorbid disorders (impulsivity, anxiety). Examining differences in functional brain organization of executive control due to anxiety and impulsivity with sensitive fMRI probes will elucidate phenotypic heterogeneity in ASD children. Guided by developmental neuroanatomical models, we will examine multiple top-down control processes and bottom-up perceptual processes that function in adaptive balance to serve goal-directed behavior. We will test the hypothesis that specific prefrontal-striato- limbic circuits, which mediate that adaptive balance, are atypical in ASD. We will manipulate component operations of top-down (voluntary, involuntary) and bottom-up (attention bias to salience) processing in 9-12 year-old high-functioning ASD children and age, Verbal IQ, and gender matched controls. Group differences and individual variation by anxiety, impulsivity, and symptom severity will be examined with confirmatory (hypothesis-driven) and exploratory (data-driven) analysis of functional networks and underlying white-matter microstructure. Aim I examines whether voluntary and involuntary control of attention is modulated by stimulus saliency (i.e., perceptual novelty, emotion) atypically in ASD. Exp 1 will examine incidental (involuntary) and intentional (voluntary) encoding of salient (novel/infrequent vs. familiar/repeated) distracters in the context of an ongoing task. Exp 2 will examine exogenous (involuntary) and endogenous (voluntary) attentional bias to salient faces (angry vs. neutral) in the Dot-probe task. Aim 2 examines whether voluntary and involuntary control of responses is modulated by stimulus domain (social-emotional or non- social) atypically in ASD. Exp 3 will examine voluntary response control (response inhibition and interference suppression) and involuntary context adaptation during a Flanker task with symbolic (non-social) stimuli. Exp 4 will examine voluntary response control during conflict varying in socio-emotional significance in a Stroop-like task. Aim 3 will examine whether intrinsic resting-state connectivity is atypical in ASD. Current research shows parallel functional organization during behavioral and resting states. We will search for resting-state correlates of component operations of executive control pooled by voluntary and involuntary conditions and domains (non-social, socio-emotional) from Exps 1-4 and determine whether they are atypical in ASD and vary by anxiety, impulsivity, and symptom severity. New knowledge from this proposal will refine models of ASD neuropathophysiology and provide targets for pharmacological and behavioral intervention.

抽象的自闭症谱系障碍 (ASD) 的特点是普遍存在社会情感和认知缺陷，即使在智力功能高的儿童。其神经病理生理学涉及由以下因素介导的执行功能障碍：前额叶皮层，但由于表型异质性高以及与前额叶皮层的共病，人们对其了解还不够。注意力和焦虑障碍以及执行功能受影响的组成过程缺乏解决能力。我们假设，由于以下特征的影响，自闭症儿童的症状表现有所不同：描述共病障碍（冲动、焦虑）。检查大脑功能组织的差异使用敏感的功能磁共振成像探针对由于焦虑和冲动而导致的执行控制的影响将阐明表型 ASD 儿童的异质性。在发育神经解剖模型的指导下，我们将检查多个自上而下的控制过程和自下而上的感知过程，在自适应中发挥作用平衡以服务于目标导向的行为。我们将检验特定前额叶-纹状体-的假设调节适应性平衡的边缘回路在自闭症谱系障碍中是不典型的。我们将操纵组件 9-12 中自上而下（自愿、非自愿）和自下而上（注意偏向显着）处理的操作岁高功能 ASD 儿童和年龄、语言智商和性别匹配的对照。群体差异焦虑、冲动和症状严重程度的个体差异将得到验证性检查功能网络和底层白质的（假设驱动）和探索性（数据驱动）分析微观结构。目标 I 检查注意力的自愿和非自愿控制是否受到以下因素的调节自闭症谱系障碍中的刺激显着性（即知觉新颖性、情感）不典型。实验 1 将检查附带的（非自愿）和有意（自愿）编码显着（新颖/不常见与熟悉/重复）的干扰因素在正在进行的任务的背景下。实验 2 将检查外源性（非自愿）和内源性（自愿）点探测任务中对显着面孔（愤怒与中立）的注意偏差。目标 2 检查是否自愿反应的无意识控制是由刺激域（社会情感或非社交）在自闭症谱系障碍中非典型。实验 3 将检查自愿反应控制（反应抑制和干扰抑制）和在具有象征性（非社交）的侧翼任务期间的非自愿上下文适应刺激。实验 4 将检验冲突期间社会情感意义不同的自愿反应控制类似斯特鲁普的任务。目标 3 将检查自闭症谱系障碍 (ASD) 中内在的静息态连接是否不典型。目前的研究表明，行为状态和休息状态下的功能组织是平行的。我们将寻找用于按自愿和非自愿汇集的执行控制组成部分操作的静息态相关性实验 1-4 中的条件和领域（非社会、社会情感）并确定它们是否非典型自闭症谱系障碍 (ASD) 中的症状因焦虑、冲动和症状严重程度而异。该提案中的新知识将得到完善 ASD 神经病理生理学模型，并为药理学和行为干预提供目标。