Tracking early emergence of sound perception impairments in FXS with multimodal fNIRS/EEG

使用多模态 fNIRS/EEG 跟踪 FXS 中早期出现的声音感知障碍

• 批准号: 10505619
• 负责人: Elizabeth Gayle Smith
• 金额: $ 15.29万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10505619
• 关键词: 10 year old; Address; Adolescent; Adult; Age; Age-Months; Anatomy; Animal Model; Area; Auditory; Auditory Perception; Auditory system; Base of the Brain; Behavioral; Biological; Biological Markers; Brain; Brain imaging; Caring; Child; Clinical; Communication impairment; Control Groups; Data; Detection; Development; Development Plans; Diagnosis; Disease; Early Intervention; Electroencephalography; Electrophysiology (science); Ethics; Etiology; Evaluation; Fragile X Syndrome; Genetic; Goals; Hearing; Hearing Tests; Heritability; Home environment; Hypersensitivity; Impairment; Individual; Infant; Intellectual functioning disability; Intervention; K-Series Research Career Programs; Language; Language Delays; Language Development; Lead; Life; Linguistics; Link; Longevity; Longitudinal Studies; Measurement; Measures; Mediator of activation protein; Mentors; Mentorship; Methods; Modeling; Nature; Neurodevelopmental Disorder; Outcome; Pattern; Phase; Phenotype; Premature Birth; Program Development; Recording of previous events; Research; Research Ethics; Research Methodology; Research Personnel; Resources; Risk; Science; Scientist; Sensory; Series; Severities; Sound Localization; Specificity; Speech; Speech Delay; Speech Development; Statistical Methods; Techniques; Testing; Time; Toddler; Training; Treatment Effectiveness; United States National Institutes of Health; Visit; analytical method; autism spectrum disorder; base; behavioral phenotyping; career; career development; early detection biomarkers; experience; functional near infrared spectroscopy; hemodynamics; high risk; human model; improved; indexing; infancy; language impairment; mental age; multimodality; neuroimaging; neuromechanism; neurophysiology; post-doctoral training; programs; relating to nervous system; response; signal processing; skills; sound; success; therapy development; tool; treatment response

Project Summary_Abstract The purpose of this K23 is to provide the training, mentorship, and research experiences needed for the applicant to become a successful independent clinical scientist with a research program focused on understanding mechanisms linking sensory anomalies, brain dysmaturation, and speech and language impairments in neurodevelopmental disorders. The training plan focuses on developing skills required to measure and understand the behavioral, auditory, and neurophysiological indices of early speech and hearing development in Fragile X Syndrome (FXS), with three specific areas of emphasis: 1) statistical methods and signal processing techniques required for cutting edge analysis of functional neurophysiology (fNIRS/EEG), 2) development of the auditory system and speech/hearing in infancy and 3) research methods and ethics for studying infants and very young children with FXS. Dr. Craig Erickson along with co-mentors Dr. John Sweeney and Dr. Lisa Hunter will provide the mentorship, training, and resources necessary to achieve the training objectives. This research program is relevant to several objectives listed in the NIH Research Plan on FXS and Associated Disorders, including but not limited to objectives 3.1 (Develop a standard battery of functional, objective measures to better characterize the emergence of the FXS phenotype across the life span and provide precise indicators of treatment effectiveness) and 3.4 (Conduct longitudinal studies of both humans and animal models to characterize the dynamic nature of the FXS phenotype across the life span and to identify moderators and mediators of the phenotype). FXS can be diagnosed in the infant and toddler years given its genetic/heritable etiology. However, current understanding of atypical maturation of brain function in FXS and its clinical manifestations is entirely based on studies of older children (5+), adolescents, and adults, at which point impairments associated with the disorder, including delays in speech and language, have been present for several years. Thus, understanding of neural mechanisms and timing of the early brain dysmaturation that lead to early delays in FXS remains limited, which in turn limits development of interventions. The proposed career development plan provides the PI with the skills to address this gap in brain-based markers of impairment in early FXS. The research plan uses EEG/fNIRS, auditory evaluations, and speech and language assessment to investigate auditory hypersensitivity and its relation to emergence of speech and language delays in FXS. This study occurs in two phases, with the first focusing on preschoolers (2-4 years) and the second, longitudinal phase focused on the infant years (0-2 years).Thus, the aim of this early career development program is to prepare the investigator to establish an independent research program focused on determining the timing and nature of brain dysmaturation that leads to early speech and communication impairment in FXS.

项目概要_摘要 这个K23的目的是提供培训，指导，和研究所需的经验， 申请人成为一名成功的独立临床科学家，其研究计划专注于 理解感觉异常、大脑发育不良、言语和语言之间的联系机制 神经发育障碍中的损伤。培训计划的重点是发展所需的技能， 测量和理解早期语言和听力的行为，听觉和神经生理学指标 脆性X综合征（FXS）的发展，有三个具体的重点领域：1）统计方法和 功能性神经生理学（fNIRS/EEG）前沿分析所需的信号处理技术，2） 婴儿期听觉系统和语言/听力的发展; 3）研究方法和伦理学， 研究患有FXS的婴儿和非常年幼的儿童。克雷格埃里克森沿着与共同导师约翰博士 斯威尼和丽莎亨特博士将提供必要的指导，培训和资源，以实现 培训目标。该研究计划与NIH研究计划中列出的几个目标有关， FXS和相关疾病，包括但不限于目标3.1（制定一套标准的 功能性、客观的测量，以更好地表征整个生命周期中FXS表型的出现 并提供治疗有效性的精确指标）和3.4（对两者进行纵向研究 人类和动物模型，以表征FXS表型在整个生命周期中的动态性质， 以鉴定表型的调节剂和介导剂）。 FXS可以在婴儿和幼儿年龄诊断，因为它的遗传/遗传病因。然而，在这方面， 目前对FXS脑功能非典型成熟及其临床表现的理解完全是 根据对年龄较大的儿童（5岁以上）、青少年和成人的研究， 这种疾病，包括说话和语言迟缓，已经存在了好几年。因此，在本发明中， 了解导致早期延迟的早期脑发育不良的神经机制和时间 FXS仍然有限，这反过来又限制了干预措施的发展。拟议职业发展计划 为PI提供解决早期FXS中基于大脑的损伤标志物的这一差距的技能。的 研究计划使用EEG/fNIRS、听觉评估以及言语和语言评估来调查 听觉超敏反应及其与FXS中言语和语言延迟出现的关系。本研究 分两个阶段进行，第一阶段主要针对学龄前儿童（2-4岁），第二阶段为纵向阶段 专注于婴儿年龄（0-2岁）。因此，这个早期职业发展计划的目的是准备 研究人员建立一个独立的研究计划，重点是确定时间和性质， 大脑发育不良，导致FXS的早期语言和沟通障碍。