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

• 批准号: 8235038
• 负责人: Chandan J Vaidya
• 金额: $ 38.71万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8235038
• 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

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）的特征是，即使在 具有智力功能的孩子。它的神经病理生理学涉及由执行功能障碍 前额叶皮层，但由于高表型异质性和合并症而没有得到很好的理解 注意力和焦虑症以及在影响执行功能的组成过程中缺乏解决方案。 我们假设症状表达因特征的影响而在ASD儿童中有所不同 表征合并症（冲动性，焦虑）。检查功能大脑组织的差异 由于焦虑和冲动性敏感的功能磁共振成像探针而导致的执行控制，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适应起作用的自下而上的感知过程 平衡服务目标行为。我们将检验以下假设： 介导这种自适应平衡的边缘电路在ASD中是非典型的。我们将操纵组件 9-12中自上而下的（自愿，非自愿）和自下而上的操作（注意显着性）处理 一岁的高功能ASD儿童和年龄，口头智商和性别匹配的控件。群体差异 以及通过确认性检查焦虑，冲动和症状严重程度的个人变化 （假设驱动）和功能网络的探索性（数据驱动）分析和潜在的白色象征 微观结构。目的我检查了注意力的自愿和非自愿控制是否受到调节 刺激显着性（即感知新颖性，情感）在ASD中是非典型的。 EXP 1将检查偶然 （非自愿）和有意的（自愿）对显着的编码 在持续的任务中。 EXP 2将检查外源性（非自愿）和内源性（自愿） 在“点探针”任务中，注意显着脸（愤怒与中立）的偏见。 AIM 2检查是否自愿 刺激领域（社会情感或非 - 社交）非典型在ASD中。 EXP 3将检查自愿反应控制（响应抑制和 干扰抑制）和非自愿上下文适应在侧翼任务中，具有象征性（非社会） 刺激。 EXP 4将检查冲突期间的自愿响应控制在社会情感意义上有所不同 一项类似于Stroop的任务。 AIM 3将检查固有的静止状态连通性在ASD中是否非典型。 当前的研究表明，行为和静止状态下的平行功能组织。我们将搜索 用于执行控制组件操作的静止状态相关，由自愿和非自愿汇总 exp 1-4的条件和域（非社会，社会情感），并确定它们是否非典型 在ASD中，随着焦虑，冲动和症状严重程度而变化。该提议的新知识将完善 ASD神经病理生理学的模型，并为药理和行为干预提供了靶标。