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: 9976034
• 负责人: Alexander Li Cohen
• 金额: $ 19.43万
• 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/9976034
• 关键词: Address; Adolescent; Adult; 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; Structure; Symptoms; Syndrome; Task Performances; Techniques; Testing; Therapeutic Intervention; Training; Trauma; Validation; Variant; acquired prosopagnosia; 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; insight; joint attention; neural circuit; neuroimaging; 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的儿童，并与残疾的异质性混合有关。 并且难以管理症状;然而，特定症状的准确定位可以允许新的 个性化治疗。为了调查面部识别能力差的常见症状，我们最近使用了一种新的 技术，“病变网络映射”，以确定一个大脑网络，是一致和具体相关的 获得性面孔失认症（中风后脸盲）患者的面部识别缺陷。 建议调查是否有一个共同的电路的transdiagnosis症状/结构的脸 确认减值，即，受后天性面容失认症影响的大脑区域是否也会在患有 自闭症谱系障碍患者表现出非典型的面部处理方式。这一建议解决了目前知识中的两个关键空白：1） 与获得性面容失认症有关的脑区也显示出ASD患者的异常， 与面部处理能力相关; 2）特定的大脑连接差异是否可以解释部分或全部 观察到的异质性，在面部诱发的大脑活动，面部识别能力，和潜在的社会影响， ASD患者。目前，没有公开的数据集包含完整的一套措施， 弥补这些差距。本申请提出了前瞻性数据收集，以解决这一差距。青少年 受试者，有和没有ASD，将接受面部处理能力，社会， 损伤和ASD症状严重沿着结构、任务和“静息状态”功能性MRI 采集招募将丰富已知有面部识别困难的受试者， 面部处理能力的范围。这一提议有可能产生生物标志物或治疗靶点 用于在人群中进行面部识别缺陷的治疗干预试验。此外，如果成功， 该项目将提供一个模型，用于识别ASD和其他疾病中存在的许多症状的神经解剖学。 神经发育障碍这种指导病人导向的职业发展奖申请直接 与国家心理健康战略目标研究所（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），为早期生物标志物的发展提供信息 预测面部识别障碍（SO2.2），并阐明潜在的机械治疗目标， 提高这些能力（战略目标3.1）。该提案还提供了重要的培训和职业机会 发展，使科恩博士成为一个独立的调查员。科恩博士有使用 神经成像工具，以了解大脑连接，并与此奖项，他将获得培训：（1）设计， 采集和分析儿科临床人群中基于MRI的研究;（2）选择，收集， 和儿科行为评估分析;（3）基于病变的神经影像学结果的验证。 最终，拟议的计划将提供一个独立的研究生涯，致力于一个坚实的基础 理解和治疗ASD和其他神经发育障碍的症状。