A child?s ability to communicate and learn through language plays a fundamental role in their cognitive, social, and functional development. Impairment in language development is shared across many neurodevelopmental disorders and can have a profound influence on a child?s future functional and developmental outcome. Unfortunately, our current understanding of the neurobiology underlying language deficits in neurodevelopmental disorders is limited, especially as it pertains to children with concurrent intellectual disability. In alignment with the strategic plan from NIDCD?s Voice, Speech, and Language program area, this project seeks to use EEG to identify neural markers (endophenotypes) associated with the progression and developmental course of speech and language impairments (Priority Area 2; Natural History and Epidemiology) in two understudied populations ? children with Fragile X Syndrome (FXS) and minimally verbal children with autism spectrum disorder (ASD) (Priority Area 3; Understudied Populations). Neural markers identified through this study, could be used as biomarkers for prognosis, and treatment monitoring of language development for children with FXS and ASD, as well as inform new treatments (Priority Area 3: Detection, Diagnosis and Hypothesis-Driven Interventions). The proposed project has the following scientific goals: (1) Characterize electrophysiological similarities and differences across preschool-aged boys with FXS, ASD with language impairment, and typically developing boys; (2) Identify and characterize neural markers of concurrent language ability in FXS and ASD; and (3) Identify and characterize neural markers of future language acquisition in FXS and ASD. To do this, we will collect EEG in three groups of boys aged 2- to 5-years-old: 30 boys with FXS, 30 boys with idiopathic ASD with language impairment (n=30), and 30 typically developing boys. At the same visit and a second visit one year apart, participants will undergo language and cognitive assessments to determine their language development. The proposed project is supported by a world class team of mentors who are experts in developmental cognitive neuroscience, language development, and advanced EEG techniques. The research environment at Boston Children?s Hospital is exceptional and the surrounding intellectual resources at Harvard, Boston University, MGH, and MIT are unmatched. My training plan is specifically designed to provide advanced training in EEG analysis, auditory processing, and language assessments for minimally verbal children, that are crucial to investigating brain-behavior relationships in these heterogenous, understudied, at-risk populations. In addition, during my training I will gain practical experience in how to successfully manage longitudinal aspects of cohort study design. By the completion of the career development award, I will have successfully applied for R01-level funding and will be ready to transition to a fully independent physician-scientist.
Using EEG to better understand the neural mechanisms of language acquisition in the context of neurodevelopmental disorders such as Fragile X Syndrome (FXS) and autism spectrum disorder (ASD) is crucial to the development of targeted drug and behavioral-based interventions to improve developmental outcomes in these children. EEG-markers identified during this study could be used as an objective measure of language prognosis, treatment monitoring during clinical trials, and ultimately development of effective therapeutics. In addition, improved understanding of the similarities and differences between FXS and ASD can help generalize these findings to the broader ASD community.
