Functional Neuroimaging of Attention in Autism

自闭症注意力的功能神经影像学

• 批准号: 8325641
• 负责人: BENJAMIN YERYS
• 金额: $ 19.24万
• 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325641
• 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.

描述（由申请人提供）：对自闭症谱系障碍的原因和治疗的研究（ASD）受到儿童和成人在我们诊所中的出现方式的极端异质性的限制。人们对不集中和多动症/冲动性症状的理解越来越多，这是ASD异质性的促成因素。我们的工作表明，这些症状的存在会导致较差的结果（更多适应不良的行为和较差的日常生活技能）。临床医生对注意力不足/多动障碍（ADHD）进行了适应诊断和治疗方法，但是这种方法表明，哌醋甲酯（即利他林）治疗ASD儿童的疗效降低了。这暗示了多动症症状的替代病理生理学。拟议的研究将使用功能性MRI和REST状态MRI以及新型的数据驱动方法，以检查患有ASD和ADHD症状儿童中破坏的脑网络。这种方法具有两个不同的优势：1）由反应抑制作用挖掘的基底神经节 - 丘脑皮层环的定义很明确，并且已知在典型ADHD的儿童中被破坏； 2）我们的数据驱动方法对大脑区域之间的潜在子组或连通性没有任何先验假设。我们将在8-10岁的ASD儿童（n = 30）且通常发展对照（n = 15）的8-10岁儿童（n = 15）的8-10岁儿童的日常环境中检查ADHD症状和抑制性控制。这些孩子将完成fMRI和静止状态扫描，以检查功能性神经解剖学和反应抑制的功能连通性。我们假设我们的数据驱动方差方法将确定一种具有ASD和ADHD症状很少的儿童模式，并且具有重要ADHD症状的ASD亚组的两种模式：一个fMRI响应抑制激活模式类似于原型ADHD儿童，以及一种与原型ADHD不同的模式。我们假设涉及响应抑制的网络之间的功能连通性将具有更大的网络内相关性和较低的网络间相关性，因为ASD组的ADHD症状和日常抑制控制障碍会减少。如果成功，我们将确定新型基于生物学的亚组来表征ASD，并确定可以在未来的治疗试验中测试的ADHD症状的新型治疗靶标。