The neuroanatomical basis for face processing deficits in autism spectrum disorder

自闭症谱系障碍面部处理缺陷的神经解剖学基础

• 批准号: 10400864
• 负责人: Alexander Li Cohen
• 金额: $ 19.5万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-11 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10400864
• 关键词: Address; Adolescent; Affect; Age; Award; Behavior assessment; Behavioral; Biological Markers; Brain; Brain region; Categories; Child; Childhood; Clinical; Cohort Studies; Collection; DSM-V; Data; Data Collection; Data Set; Development; Diagnosis; Diagnostic; Disease; Face; Face Processing; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Gender; Goals; Impairment; Individual; Individual Differences; K-Series Research Career Programs; Knowledge; Left; Lesion; Light; Link; Literature; Location; Magnetic Resonance Imaging; Maps; Measures; Mediating; Mediation; Mediator of activation protein; Mentors; Methods; Modeling; National Institute of Mental Health; Neuroanatomy; Neurodevelopmental Disorder; Participant; Patients; Pattern; Perception; Performance; Population; Prosopagnosia; Research; Research Personnel; Rest; Severities; Stroke; Symptoms; Syndrome; Task Performances; Techniques; Testing; Therapeutic Intervention; Training; Trauma; Validation; Variant; acquired prosopagnosia; adult with autism spectrum disorder; autism spectrum disorder; autistic children; base; biomarker development; career; career development; cognitive control; common symptom; connectome; design; developmental disease; developmental prosopagnosia; early detection biomarkers; experience; frontal lobe; fusiform face area; gaze; improved; individualized medicine; individuals with autism spectrum disorder; insight; joint attention; neural circuit; neuroimaging; noninvasive brain stimulation; novel; novel therapeutic intervention; patient oriented; post stroke; predictive marker; programs; prospective; recruit; showing emotion; social; social communication; symptom management; symptom treatment; targeted therapy trials; tool; training opportunity

Autism Spectrum Disorder (ASD) affects 1:59 children and is associated with a heterogeneous mix of disabling and difficult to manage symptoms; however, accurate localization of specific symptoms may allow for novel individualized therapies. To investigate the common symptom of poor face recognition, we recently used a new technique, `lesion network mapping', to identify a brain network that is consistently and specifically associated with face recognition deficits in patients with acquired prosopagnosia (face blindness after stroke).This proposal investigates whether there a common circuit for the transdiagnostic symptom/construct of face recognition impairment, i.e., are brain regions affected by acquired prosopagnosia also affected in children with ASD who display atypical face processing. This proposal addresses two key gaps in current knowledge: 1) do brain regions implicated by acquired prosopagnosia also demonstrate abnormalities in patients with ASD that correlate with face processing ability; and 2) do specific brain connectivity differences explain some or all of the observed heterogenicity in face-evoked brain activity, face-recognition abilities, and potentially social affect in individuals with ASD. Presently, no publicly available dataset contains the complete set of measures to address these gaps. This application proposes prospective data collection to address this gap. Adolescent subjects, with and without ASD, will undergo behavioral assessments of face processing ability, social impairment, and ASD symptom severity along with structural, task, and `resting-state' functional MRI acquisition. Recruitment will be enriched with subjects with known face recognition difficulties to capture a range of face processing abilities. This proposal has the potential to generate biomarkers or treatment targets for trials of therapeutic intervention for face recognition deficits across populations. Furthermore, if successful, this project will provide a model for identifying the neuroanatomy for many symptoms present in ASD and other neurodevelopmental disorders. This Mentored Patient-Oriented Career Development Award application directly aligns with the National Institute of Mental Health Strategic Objectives (SOs), as it will help define the connectome abnormalities of face recognition impairment (SO1.3), inform the development of early biomarkers predictive of face recognition impairment (SO2.2), and shed light on potential mechanistic treatment targets to improve these abilities (SO3.1). The proposal also provides important opportunities for training and career development to enable Dr. Cohen to become an independent investigator. Dr. Cohen has experience in using neuroimaging tools to understand brain connectivity, and with this award, he will gain training in: (1) the design, acquisition, and analysis of a MRI-based study in a pediatric clinical population; (2) the selection, collection, and analysis of pediatric behavioral assessments; and (3) the validation of lesion-based neuroimaging findings. Ultimately, the proposed program will provide a strong foundation for an independent research career devoted to the understanding and treatment of symptoms in ASD and other neurodevelopmental disorders.

自闭症谱系障碍(ASD)影响1：59名儿童，并与不同类型的残疾相关 和难以管理的症状；然而，对特定症状的准确定位可能允许新的 个体化治疗。为了研究人脸识别不良的常见症状，我们最近使用了一种新的 一种名为“病变网络图”的技术，用来识别一致且特定关联的大脑网络。 获得性面孔失认症患者的面部识别缺陷(中风后脸部失明)。 建议调查脸部的跨诊断症状/结构是否存在共同的回路 认知障碍，也就是说，后天性失认症影响的大脑区域也会受到 表现出非典型面部处理的自闭症。这项建议解决了当前知识中的两个关键差距：1)做 获得性面容失认症涉及的大脑区域也显示出ASD患者的异常 与面部处理能力相关；以及2)特定的大脑连接性差异是否解释了部分或全部 观察到面孔诱发的大脑活动、面孔识别能力和潜在的社会影响的异质性 患有自闭症的个体。目前，没有公开可用的数据集包含完整的衡量标准集，以 填补这些差距。该应用程序提出了前瞻性数据收集来解决这一差距。青少年 受试者，无论是否患有自闭症，都将接受面部处理能力、社交能力的行为评估。 损害、ASD症状严重程度以及结构、任务和静息状态的功能MRI 收购。招聘将增加已知人脸识别困难的受试者，以获取 一系列人脸处理能力。这项提议有可能产生生物标记物或治疗靶点。 用于对人群中的面部识别缺陷进行治疗干预的试验。此外，如果成功， 该项目将为识别ASD和其他疾病中存在的许多症状的神经解剖学提供一个模型 神经发育障碍。直接指导以病人为导向的职业发展奖申请 与国家精神卫生研究所战略目标(SOS)保持一致，因为它将有助于定义 面部识别障碍的连接体异常(SO1.3)，提示早期生物标志物的发展 面部识别损害的预测(SO2.2)，并阐明潜在的机械治疗目标 提高这些能力(SO3.1)。该提案还为培训和职业生涯提供了重要的机会 发展，使科恩博士成为一名独立的调查员。科恩博士在使用 了解大脑连接的神经成像工具，有了这个奖，他将获得以下方面的培训：(1)设计， 在儿科临床人群中获取和分析基于MRI的研究；(2)选择、收集、 和儿科行为评估的分析；以及(3)基于病变的神经影像发现的有效性。 最终，拟议的计划将为致力于独立研究的职业生涯提供坚实的基础 了解和治疗自闭症和其他神经发育障碍的症状。