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: 7874721
• 负责人: Chandan J Vaidya
• 金额: $ 39.06万
• 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/7874721
• 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; 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; public health relevance; response; social; theories; trait; white matter

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: This project aims to elucidate individual differences in functional brain organization of higher cognition in 9-12 year old children with Autism Spectrum Disorders with normal intellectual function. It will use brain imaging to examine whether functional brain organization of executive function varies by anxiety and impulsivity that are reflected in symptoms of the disorder. Knowledge gained from proposed studies will refine clinical characterization and reveal new targets for pharmacological and behavioral treatment for Autism Spectrum Disorders.

描述（由申请人提供）：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，即使在智力水平较高的儿童中也是如此。其神经病理生理学涉及由前额叶皮层介导的执行功能障碍，但由于表型异质性高、注意力和焦虑障碍的共病以及执行功能受影响的组成过程缺乏解决方案，人们对其还没有很好的理解。我们假设，由于共病特征（冲动、焦虑）的影响，自闭症儿童的症状表现有所不同。使用敏感的功能磁共振成像探针检查由于焦虑和冲动而导致的执行控制功能性大脑组织的差异，将阐明自闭症谱系障碍儿童的表型异质性。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，这些过程在适应性平衡中发挥作用，以服务于目标导向的行为。我们将检验这样一个假设：介导适应性平衡的特定前额叶-纹状体-边缘回路在自闭症谱系障碍中是非典型的。我们将操纵 9-12 岁高功能 ASD 儿童的自上而下（自愿、非自愿）和自下而上（注意力偏向于显着性）处理的组件操作以及年龄、言语智商和性别匹配控制。将通过对功能网络和底层白质微观结构的验证性（假设驱动）和探索性（数据驱动）分析来检查焦虑、冲动和症状严重程度造成的群体差异和个体差异。目标 I 检查自闭症谱系障碍中，注意力的自愿和非自愿控制是否受到刺激显着性（即知觉新颖性、情感）的调节。实验 1 将检查正在进行的任务背景下对显着（新颖/不常见与熟悉/重复）干扰因素的偶然（非自愿）和有意（自愿）编码。实验 2 将检查点探测任务中对显着面孔（愤怒与中立）的外源（非自愿）和内源（自愿）注意偏差。目标 2 检查自闭症谱系障碍中，对反应的自愿和非自愿控制是否受到刺激领域（社会情感或非社会）的非典型调节。实验 3 将检查在具有象征性（非社交）刺激的侧卫任务期间的自愿反应控制（反应抑制和干扰抑制）和非自愿情境适应。实验 4 将在类似斯特鲁普的任务中检查社会情感意义不同的冲突期间的自愿反应控制。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。我们将从实验 1-4 中寻找由自愿和非自愿条件和领域（非社会、社会情感）汇集的执行控制组件操作的静息态相关性，并确定它们是否在自闭症谱系障碍中不典型，并因焦虑、冲动而变化，以及症状的严重程度。该提案的新知识将完善 ASD 神经病理生理学模型，并为药理学和行为干预提供目标。公共健康相关性：该项目旨在阐明具有正常智力功能的 9-12 岁自闭症谱系障碍儿童的高级认知功能大脑组织的个体差异。它将使用大脑成像来检查执行功能的功能性大脑组织是否因疾病症状所反映的焦虑和冲动而变化。从拟议研究中获得的知识将完善临床特征，并揭示自闭症谱系障碍药物和行为治疗的新目标。