Brain Systems Underlying Episodic Memory for Social Stimuli in Childhood Autism

描述（由申请人提供）：这是一份NIH独立之路PI奖（K99/R00）的申请，题为“儿童自闭症中社会刺激情景记忆的大脑系统”。本研究的总体目标是了解自闭症谱系障碍（ASD）儿童对社会刺激异常情景记忆的神经基础。ASD是一种神经发育障碍，其特征是终生缺乏社交能力。对社会相关事件的情景记忆受损在自闭症患者中也很常见，这种损伤对成功的社会互动和长期社会关系的形成非常有害。了解异常情景记忆，特别是与社会刺激有关的情景记忆，有可能为这种疾病的性质和病因提供新的见解。该候选人将使用最先进的功能和弥散张量脑成像，结合新的记忆范式和多元方法，比较ASD儿童和年龄、性别和智商匹配的正常发育儿童在社会和非社会刺激下情景记忆的神经相关性。记忆编码，检索和巩固过程将被检查。具体目的是：(1)探讨ASD儿童（K99期）情景记忆编码和社会刺激检索的非典型脑系统；(2)探讨ASD儿童（K99期和R00期）情景记忆编码和提取的非典型脑连通性；(3)研究ASD儿童情景记忆巩固（即对社会刺激的长期记忆保留数天后）的非典型脑系统和连通性，并确定哪些记忆过程和大脑测量是ASD儿童（R00期）记忆功能和社会缺陷的临床和神经心理学评估最可靠的预测因子。本研究的发现将促进我们对情景记忆功能障碍的大脑基础及其对ASD社会缺陷的贡献的理解。这些知识将为自闭症儿童的早期干预和补救教育提供信息。候选人将在K99阶段接受严格的教育、培训和职业发展计划，以增加ASD临床研究方面的专业知识，并结合结构弥散张量成像对功能性脑成像数据进行多元模式分类分析。候选人将接受临床心理学、精神病学、发育和认知神经科学领域的顶尖专家的指导和培训，并将获得成功治疗自闭症儿童所需的临床评估方面的重要经验。K99阶段的知识和技能将使候选人成为独立的研究者，并在R00阶段完成后续的创新研究。在这两个阶段完成拟议的研究将允许候选人通过连接临床和认知神经科学以及自闭症研究来启动严格的研究计划，从而获得具有竞争力的NIH R01资助。

DESCRIPTION (provided by applicant): This is an application for an NIH Pathway to Independence PI Award (K99/R00), entitled "Brain systems underlying episodic memory for social stimuli in childhood autism". The overall goal of the proposed research is to understand the neural basis of aberrant episodic memory for social stimuli in children with autism spectrum disorders (ASD). ASD is a neurodevelopmental disorder characterized by life-long deficits in social interactions. Impaired episodic memory for events of social relevance has also been commonly seen in individuals with ASD and such impairments can be highly detrimental to successful social interactions and the formation of long-term social relationships. Understanding aberrant episodic memory, particularly as it pertains to social stimuli, has the potential to provie new insights into the nature and etiology of the disorder. The candidate will use state-of-the-art functional and diffusion tensor brain imaging in conjunction with novel memory paradigms and multivariate methods to compare the neural correlates of episodic memory for social and nonsocial stimuli in children with ASD and typically developing children matched on age, gender and IQ. Memory encoding, retrieval and consolidation processes will be examined. The Specific Aims are: (1) To investigate atypical brain systems underlying episodic memory encoding and retrieval for social stimuli in children with ASD (K99 phase); (2) To investigate atypical brain connectivity underlying episodic memory encoding and retrieval in children with ASD (K99 and R00 phases); (3) To investigate atypical brain systems and connectivity underlying episodic memory consolidation (i.e., long-term retention of memories for social stimuli after several days) in children with ASD, and to determine which memory processes and brain measures are the most reliable predictors of clinical and neuropsychological assessments of memory functioning and social deficits in children with ASD (R00 phase). Findings from this research will advance our understanding of the brain basis of episodic memory dysfunction and its contribution to social deficits in ASD. This knowledge will inform early intervention and remedial education in children with ASD. The candidate will undergo a rigorous education, training, and career development plan in the K99 phase to increase expertise in clinical aspects of ASD research, and multivariate pattern classification analysis of functional brain imaging data in conjunction with structural diffusion tensor imaging. The candidate will be mentored and trained by leading experts in clinical psychology, psychiatry, developmental and cognitive neuroscience, and will gain critical experience in clinical assessments necessary for successfully working with children with ASD. This knowledge and skills during the K99 phase will enable the candidate to become an independent investigator and accomplish the follow-up innovative studies in the R00 phase. Accomplishing the proposed research in the two phases will allow the candidate to launch a rigorous research program by bridging clinical and cognitive neuroscience, and autism research, leading to a competitive NIH R01 grant.