Functional Imaging of Flexibility in Autism: Informed by SLC6A4

自闭症灵活性的功能成像：由 SLC6A4 提供信息

• 批准号: 7989845
• 负责人: BENJAMIN YERYS
• 金额: $ 12.9万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-16 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7989845
• 关键词: Address; Age; Alleles; Anatomy; Architecture; Arts; Attention; Autistic Disorder; Behavior; Behavioral; Behavioral Genetics; Biological Markers; Blood specimen; Brain; Brain region; Centers for Disease Control and Prevention (U.S.); Child; Clinical; Cognitive; Collaborations; Control Groups; Corpus striatum structure; Data; Development; Development Plans; Diagnostic; Disease; Environment; Exhibits; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genes; Genetic; Genetic Techniques; Genome; Genomics; Genotype; Goals; Heterogeneity; Image; Individual; Intervention; Lead; Magnetic Resonance Imaging; Maps; Medical center; Mentors; Methods; Modeling; Motor; Nature; Neuroanatomy; Neurobiology; Neurocognitive; Neurologist; Neuropsychology; Neurosciences; Parietal; Parietal Lobe; Pediatric Hospitals; Performance; Philadelphia; Process; Reaction Time; Reading; Recruitment Activity; Relative (related person); Research; Research Personnel; Research Project Grants; Research Training; Rest; Sampling; Scientist; Serotonin; Societies; Stimulus; Stream; Structure; Symptoms; Techniques; Technology; Testing; Thinking; Training; Universities; Variant; Work; autism spectrum disorder; base; career development; disorder control; disorder risk; flexibility; genetic analysis; indexing; insight; interest; member; neglect; neuromechanism; neuropsychological; novel; prevent; programs; psychologic; public health relevance; relating to nervous system; research study; response; serotonin transporter; social

DESCRIPTION (provided by applicant): The immediate goals of this application include: training the candidate to become an independent clinical- researcher, and to addressing the brain (and genetic) basis of a cardinal, but neglected restricted, repetitive symptoms of autism spectrum disorders (ASD). Long term goals include: developing a model for integrative research, informing our understanding of the causes of ASD, and advancing our ability to test and target treatments for ASD. The research project uses well established neuroscience methods (functional MRI and genotyping) to investigate brain regions and genes involved in restricted, repetitive behavior and interest symptoms in ASD. Cognitive flexibility serves as a window into this symptom cluster, and the proposed studies address a limitation of past work by carefully parsing flexibility into its core components in children with ASD. Children with and without ASD will be genotyped for a serotonin transporter gene implicated in both ASD and cognitive flexibility and will participate in functional MRI and psychological batteries that assess cognitive flexibility and ASD symptoms. Children with ASD and the risk allele for the serotonin transporter gene are predicted to make more errors on flexibility tasks and show greater deviance in the structure and function of brain regions activated. The career development plan includes cross-disciplinary training in advanced MRI techniques, neuroanatomy, neurobiology, genetics, neuropsychology, and imaging genomics; training comes from formal didactics, directed readings and laboratoryexperiences with a distinguished panel of expert co-mentors with a neurologist as lead mentor. Research environment: The candidate's main training and research will occur in a burgeoning, collaborative autism research program at Children's National Medical Center and Georgetown University, and he will receive in-depth advanced training from established institutional and personal collaborations with scientists at the Children's Hospital of Philadelphia and Stanford University. PUBLIC HEALTH RELEVANCE: According to the Center for Disease Control, 1 in 150 children in the US has autism. Repetitive behaviors and rigid, inflexible thinking are cardinal symptoms of the disorder and prevent many otherwise high funcitoning people from being poductive members of main stream society. Yet our understanding of these symptoms remains limited at cognitive, brain, and genetic levels of analysis. The proposed work seeks to define neural and genetic contributors to this cluster of autism symptoms in order to help us pursue the causes of, and target interventions to treat, these core autism deficits.

描述（由申请人提供）：本申请的直接目标包括：培训候选人成为一名独立的临床研究员，并解决自闭症谱系障碍的主要但被忽视的限制性重复症状的大脑（和遗传）基础（自闭症谱系障碍）。长期目标包括：开发综合研究模型，让我们了解自闭症谱系障碍的原因，并提高我们测试和针对自闭症谱系障碍治疗的能力。该研究项目使用成熟的神经科学方法（功能性 MRI 和基因分型）来研究与自闭症谱系障碍的受限、重复行为和兴趣症状有关的大脑区域和基因。认知灵活性是了解这一症状群的一个窗口，拟议的研究通过仔细地将自闭症儿童的灵活性解析为其核心组成部分来解决过去工作的局限性。患有和不患有 ASD 的儿童将接受与 ASD 和认知灵活性有关的血清素转运蛋白基因分型，并将参加功能性 MRI 和心理电池测试，以评估认知灵活性和 ASD 症状。患有自闭症谱系障碍和血清素转运蛋白基因风险等位基因的儿童预计会在灵活性任务中犯更多错误，并且在激活的大脑区域的结构和功能上表现出更大的偏差。职业发展计划包括先进MRI技术、神经解剖学、神经生物学、遗传学、神经心理学和影像基因组学的跨学科培训；培训来自正式的教学、定向阅读和实验室经验，由杰出的专家共同导师组成，并以神经科医生为首席导师。研究环境：候选人的主要培训和研究将在国家儿童医学中心和乔治城大学的一个新兴的自闭症合作研究项目中进行，他将从与乔治城儿童医院的科学家建立的机构和个人合作中接受深入的高级培训。费城和斯坦福大学。 公共卫生相关性：根据疾病控制中心的数据，美国每 150 名儿童中就有 1 名患有自闭症。重复的行为和僵化、不灵活的思维是这种疾病的主要症状，并阻止许多其他高功能的人成为主流社会的积极成员。然而，我们对这些症状的理解仍然仅限于认知、大脑和遗传分析水平。拟议的工作旨在定义导致这组自闭症症状的神经和遗传因素，以帮助我们追寻这些核心自闭症缺陷的原因，并制定有针对性的干预措施来治疗这些缺陷。