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

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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.