Project Summary/Abstract The elevated risk of language and reading disorders (as high as 60%) among children with isolated cleft of the lip and/or palate (iCL/P) is a significant clinical concern, substantiated by research since the 1980’s. These disabilities, while not in the range of intellectual dysfunction, do result in academic achievement problems and lower rates of college attendance. Neuroimaging work in children, adolescents, and young adults with iCL/P has identified an association between these deficits and patterns of aberrant neural development and disrupted activation during reading tasks. The critical next step in this line of work is to determine the etiology of these language deficits and the associated neural patterns. Current hypotheses postulate that deficits may be due to events very early in life, including 1) repeated exposure to anesthesia, 2) airway obstruction/reduced oxygenation, and 3) genetic/biological factors disrupting neural migration and brain development. To fully evaluate these theories, imaging work needs to be done on infants before and after their first surgery, with information on oxygenation, pre-speech functioning, and neural development obtained in tandem. The lack of such research is a crucial gap in the field, precluding essential information needed to inform clinical decisions that may improve these outcomes (e.g., treatment protocols and appropriate interventions). In the proposed study, infants with iCL/P and unaffected controls will undergo assessment at 2, 6-8, and 14-16 months of age; providing pre- and post-surgery measures for infants with iCL/P. At each time point, innovative techniques of brain imaging (through MRI and fNIRS) and multi-modal assessment of speech/language (vocal recordings and clinical ratings) will be combined with continuous overnight pulse oximetry and systematic and structured medical chart review (for information on anesthesia exposure, clinically mandated sleep studies, medical interventions, and audiology assessments). Through an R56 (NIDCR), the PI and research team have demonstrated feasibility of this protocol with baseline data on 16 participants to date. Initial data reflects patterns of immature pre-speech development, disrupted cortical growth and activation, and more desaturation events for those with iCL/P prior to exposure to anesthesia. The current project aims to: 1) Use baseline data to assess the effects of cleft presence and overnight desaturation events on brain structure/function and pre-speech/language measures before exposure to anesthesia; 2) Use data from all timepoints to assess the longitudinal effects of desaturation events and exposure to anesthesia on neural and language outcomes for patients with and without iCL/P; and 3) Evaluate the relationship between measures of neural structure/function and language outcomes. The longitudinal approach and novel measures of pre-speech and neural functioning will significantly contribute to the understandi...