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: 7731942
• 负责人: Chandan J Vaidya
• 金额: $ 40.37万
• 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/7731942
• 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; Operative Surgical Procedures; 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; 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）的特征是，即使在具有智力较高的儿童中，也普遍存在的社会情感和认知缺陷。它的神经病理生理学涉及前额叶皮层介导的执行功能障碍，但由于高表型异质性和合并症而伴随着注意力和焦虑症，并且缺乏在受影响的执行功能的成分过程中缺乏分辨率，因此并未得到充分理解。我们假设症状表达在ASD儿童中由于特征性疾病的特征（冲动性，焦虑）的影响而有所不同。检查由于焦虑和使用敏感的FMRI探针冲动而导致的高管控制功能性大脑组织的差异将阐明ASD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，这些过程在自适应平衡中起作用，以服务于目标指导行为。我们将检验以下假设：介导这种适应性平衡的特定前额叶 - 边缘电路在ASD中是非典型的。我们将操纵自上而下的（自愿，非自愿）和自下而上的（注意显着性）处理的组件操作，以9-12岁的高功能ASD儿童和年龄，言语智商和性别匹配的控制措施。通过确认性（假设驱动）和探索性（数据驱动）分析功能网络和基本的白色 - 一种微观结构，将检查焦虑，冲动和症状严重程度的群体差异和个人变化。 AIM I研究了刺激显着性（即感知新颖性，情感）是否在ASD中进行了自愿和非自愿控制。 EXP 1将检查在持续的任务的背景下，偶然的（非自愿）和故意（自愿）编码显着的（新颖/不经常与熟悉/重复）的干扰物。 EXP 2将检查DOT探针任务中对显着面（愤怒与中性）的外源性（自愿）和内源性（自愿）注意偏见。 AIM 2检查了对响应的自愿和非自愿控制是否通过ASD中非典型的刺激领域（社会情感或非社会）调节。 EXP 3将检查自愿反应控制（反应抑制和干扰抑制）和具有符号（非社会）刺激的侧翼任务期间的非自愿环境适应。 EXP 4将检查冲突期间的自愿响应控制在类似于Stroop的任务中的社会情感意义各异。 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。我们将搜索执行控制的组件操作的休息状态相关性，这些操作由Exp 1-4的自愿和非自愿条件和领域（非社会，社会情感）汇总，并确定它们在ASD中是非典型的，并且因焦虑，冲动性，冲动性和症状严重程度而变化。该提案的新知识将完善ASD神经病理生理学的模型，并为药理学和行为干预提供目标。公共卫生相关性：该项目旨在阐明在9至12岁患有正常智力功能的自闭症谱系障碍的儿童的功能性脑组织中的个体差异。它将使用大脑成像检查执行功能的功能性大脑组织是否会随着疾病症状反映的焦虑和冲动性而有所不同。从建议的研究中获得的知识将完善临床表征，并揭示自闭症谱系障碍药理和行为治疗的新靶标。