Functional Neuroimaging of Attention in Autism

自闭症注意力的功能神经影像学

• 批准号: 8030961
• 负责人: BENJAMIN YERYS
• 金额: $ 23.42万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8030961
• 关键词: 10 year old; Address; Adult; Analysis of Variance; Attention; Attention deficit hyperactivity disorder; Autistic Disorder; Basal Ganglia; Behavior; Behavioral; Biological; Biological Markers; Biology; Brain; Brain region; Child; Childhood; Clinic; Clinical; Cognitive; Complex; Control Groups; Data; Diagnosis; Diagnostic; Event; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genetic; Genotype; Goals; Heterogeneity; Hyperactive behavior; Imaging Techniques; Impairment; Impulsivity; Investigation; Life; Link; Magnetic Resonance Imaging; Maps; Methods; Methylphenidate; Motor; Neuroanatomy; Neurobiology; Neurophysiology - biologic function; Outcome; Parents; Pattern; Population; Problem behavior; Process; Relative (related person); Reporting; Research; Rest; Ritalin; Scanning; Source; Strategic Planning; Subgroup; Symptoms; Testing; Therapy Clinical Trials; Time; Work; autism spectrum disorder; base; endophenotype; hemodynamics; improved; inattention; independent component analysis; innovation; meetings; neural circuit; neural patterning; neuroimaging; novel; relating to nervous system; response; segregation; skills; tool; trait; treatment response

DESCRIPTION (provided by applicant): Research into the causes and treatments of Autism Spectrum Disorders (ASD) are limited by extreme heterogeneity in how children and adults present at our clinics. There is an increasing appreciation for inattention and hyperactivity/impulsivity symptoms as a contributing factor to heterogeneity in ASD. Our work shows that the presence of these symptoms leads to worse outcomes (more maladaptive behaviors and poorer daily living skills). Clinicians have adapted diagnostics and treatments from Attention Deficit/Hyperactivity Disorder (ADHD), but this approach has shown reduced efficacy of methylphenidate (i.e., ritalin) treatment in children with ASD. This suggests an alternative pathophysiology for the ADHD symptoms. The proposed study will use functional MRI and rest state MRI along with novel, data-driven methods to examine brain networks disrupted in children with ASD and ADHD symptoms. This approach has two distinct advantages: 1) a basal ganglia-thalamocortical loop tapped by response inhibition is well- defined and known to be disrupted in children with prototypical ADHD; and 2) our data-driven methods make no a priori assumptions about potential sub-groups identified or connectivity among brain regions. We will examine the presence of ADHD symptoms and inhibitory control in everyday settings in 8-10-year-old children with ASD (n=30) and typically developing controls (n=15). These children will complete fMRI and resting state scans to examine functional neuroanatomy and functional connectivity of response inhibition. We hypothesize that our data-driven variance methods will identify one pattern of children with ASD and few ADHD symptoms and two patterns of ASD subgroups with significant ADHD symptoms: one group with fMRI response inhibition activation patterns similar to prototypical ADHD children, and one group with patterns distinct from prototypical ADHD. We hypothesize that functional connectivity among networks involved in response inhibition will have greater intra-network correlations and lower inter-network correlations as ADHD symptoms and everyday inhibitory control impairments decrease in the ASD group. If successful, we will identify novel biologically- based subgroups to characterize ASD, as well as identify novel treatment targets for ADHD symptoms that can be tested in future therapeutic trials. PUBLIC HEALTH RELEVANCE: Research into the causes and treatments of ASD is limited by extreme heterogeneity, and no studies to our knowledge have attempted to reduce this heterogeneity at the neural level by examining the impact of comorbid ADHD symptoms. Also, our use of new, data-driven analysis methods will identify subgroups of ASD that is based on biology. If successful, these new subgroups of children with ASD will reduce heterogeneity for future genetic investigations and serve as a guide for future therapeutic trials for reducing ADHD symptoms in ASD.

描述（由申请人提供）：对自闭症谱系障碍 (ASD) 的病因和治疗的研究受到儿童和成人在我们诊所的表现极端异质性的限制。人们越来越认识到注意力不集中和多动/冲动症状是导致自闭症谱系障碍异质性的一个因素。我们的工作表明，这些症状的存在会导致更糟糕的结果（更多的适应不良行为和更差的日常生活技能）。临床医生已经调整了注意力缺陷/多动障碍 (ADHD) 的诊断和治疗方法，但这种方法显示哌醋甲酯（即利他林）治疗 ASD 儿童的疗效降低。这表明多动症症状有另一种病理生理学。拟议的研究将使用功能性 MRI 和静息态 MRI 以及新颖的数据驱动方法来检查患有自闭症谱系障碍 (ASD) 和多动症 (ADHD) 症状的儿童的大脑网络是否受到干扰。这种方法有两个明显的优点：1）通过反应抑制激活的基底神经节-丘脑皮质环路是明确的，并且已知在患有典型 ADHD 的儿童中会被破坏； 2）我们的数据驱动方法没有对已识别的潜在亚组或大脑区域之间的连接性做出先验假设。我们将检查 8-10 岁患有自闭症谱系障碍 (ASD) 儿童 (n=30) 和典型发育对照儿童 (n=15) 的日常环境中是否存在 ADHD 症状和抑制控制。这些孩子将完成功能磁共振成像和静息态扫描，以检查功能性神经解剖学和反应抑制的功能连接。我们假设我们的数据驱动方差方法将识别一种患有 ASD 和很少 ADHD 症状的儿童模式，以及两种具有明显 ADHD 症状的 ASD 亚组模式：一组具有与典型 ADHD 儿童相似的 fMRI 反应抑制激活模式，另一组具有与典型 ADHD 不同的模式。我们假设，随着 ASD 组 ADHD 症状和日常抑制控制障碍的减少，参与反应抑制的网络之间的功能连接将具有更大的网络内相关性和更低的网络间相关性。如果成功，我们将确定新的基于生物学的亚组来表征自闭症谱系障碍，并确定可在未来的治疗试验中测试的 ADHD 症状的新治疗目标。 公共卫生相关性：对 ASD 病因和治疗的研究受到极端异质性的限制，据我们所知，没有研究试图通过检查共病 ADHD 症状的影响来减少神经水平上的这种异质性。此外，我们使用新的数据驱动分析方法将识别基于生物学的 ASD 亚组。如果成功，这些新的自闭症儿童亚组将减少未来基因研究的异质性，并为未来减少自闭症多动症症状的治疗试验提供指导。