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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

基本信息

批准号：
10610369
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
项目类别：
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/10610369
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 Link Literature Location Magnetic Resonance Imaging Maps Measures Mediating Mediation Mediator 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 biomarker development career career development cognitive control common symptom connectome design developmental disease developmental prosopagnosia direct application 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

项目摘要

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，并与多种残疾相关且难以控制症状；然而，对特定症状的准确定位可能会带来新的发现个体化治疗。为了调查人脸识别不佳的常见症状，我们最近使用了一种新的技术“病变网络映射”，用于识别一致且特定相关的大脑网络患有获得性面容失认症（中风后面部失明）的患者存在面部识别缺陷。提案调查跨诊断症状/面部结构是否存在共同回路识别障碍，即，受后天性面盲症影响的大脑区域是否也受到患有以下疾病的儿童的影响：自闭症谱系障碍者表现出非典型的面部处理。该提案解决了当前知识中的两个关键差距：1）与获得性面容失认症有关的大脑区域也表现出自闭症谱系障碍患者的异常与人脸处理能力相关； 2）特定的大脑连接差异是否可以解释部分或全部观察到面部诱发的大脑活动、面部识别能力和潜在社会影响的异质性患有自闭症谱系障碍 (ASD) 的人。目前，没有公开可用的数据集包含完整的衡量标准解决这些差距。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谱系障碍（ASD），都将接受面部处理能力、社交能力等行为评估。损伤和 ASD 症状严重程度以及结构、任务和“静息态”功能 MRI 获得。将丰富招募具有已知人脸识别困难的受试者，以捕获面部处理能力的范围。该提案有可能产生生物标志物或治疗目标针对不同人群的面部识别缺陷进行治疗干预试验。此外，如果成功的话，该项目将提供一个模型，用于识别自闭症谱系障碍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。此指导直接以患者为中心的职业发展奖申请与国家心理健康研究所战略目标 (SO) 保持一致，因为它将有助于定义面部识别障碍的连接组异常（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），并揭示潜在的机械治疗目标提高这些能力（SO3.1）。该提案还提供了重要的培训和职业机会使科恩博士成为一名独立调查员。 Cohen 博士有使用经验神经影像工具来理解大脑的连接性，凭借这个奖项，他将获得以下方面的培训：（1）设计，在儿科临床人群中进行基于 MRI 的研究的采集和分析； (2)选择、收集、儿科行为评估和分析； (3) 基于病变的神经影像学结果的验证。最终，拟议的计划将为致力于独立研究生涯提供坚实的基础了解和治疗自闭症谱系障碍和其他神经发育障碍的症状。