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

项目摘要_摘要 本K23课程的目的是提供所需的培训、指导和研究经验 申请者将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、大脑发育不成熟以及言语和语言之间的联系机制 神经发育障碍的损害。培训计划的重点是发展所需的技能 测量和了解早期言语和听力的行为、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 功能神经生理学前沿分析所需的信号处理技术(fNIRS/EEG)，2) 婴儿期听觉系统和言语/听力的发展和3)研究方法和伦理学 研究患有FXS的婴儿和幼儿。克雷格·埃里克森博士和共同导师约翰博士 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。这项研究计划与美国国立卫生研究院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(开发标准电池 功能、客观的措施，以更好地表征FXS表型在整个生命周期的出现 并提供治疗效果的准确指标)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和 以确定表型的调节因子和中介因子)。 鉴于其遗传/遗传病因，FXS可以在婴儿和蹒跚学步的儿童时期被诊断出来。然而， 目前对FXS脑功能不典型成熟及其临床表现的认识是完全不同的 基于对年龄较大的儿童(5)、青少年和成年人的研究，在这一点上，损害与 这种障碍，包括语言和语言的延迟，已经存在了几年。因此， 早期脑发育不成熟导致早期脑发育迟缓的神经机制和时间的理解 外汇储备仍然有限，这反过来又限制了干预措施的发展。拟议的职业发展计划 为PI提供技能，以解决早期FXS中基于大脑的损害标记物的这一缺口。这个 研究计划使用EEG/fNIRS、听觉评估以及言语和语言评估来调查 FXS患者听觉超敏反应及其与言语和语言延迟出现的关系本研究 分两个阶段进行，第一个阶段侧重于学龄前儿童(2-4岁)，第二个阶段为纵向阶段 重点放在婴儿期(0-2岁)。因此，这一早期职业发展计划的目标是为 调查员建立了一个独立的研究计划，重点是确定时间和性质 大脑发育不成熟，导致FXS患者早期言语和沟通障碍。

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.