No other period in human life matches the magnitude and astonishing increase in neural functionalcapacity as the transition from neonate to infant to toddler. Within a month or two following birth, the infantbegins to smile and around first birthday begins to speak. Soon thereafter he coordinates speech andgesture in order to garner the attention of others. By the time he is two, he can speak in short sentences andhas a rich repertoire of socio-emotional responding.Of all autism biology, the greatest mystery is what neural malfunction fails to provide this leap insocial, emotional and language capacity.The only safe and powerful method for observing human neural function directly is functional MRI.While there are now thousands of fMRI studies in mature humans, not a single fMRI experiment hasattempted to discover the neurofunctional bases of this incredible achievement in typical infants or itsprofound failure in the autistic infant.We have performed ground-breaking pilot fMRI studies of typical and autistic toddlers mapping for thefirst time the regions of the brain that are involved in responding to language, social and emotion sounds.We have done this in the only way feasible: while the toddler is in natural sleep and not moving. This methodof mapping neural function and malfunction allows testing to be done comparably regardless ofdevelopmental age or level of mental or behavioral ability; infants at all ages and levels of functioning can bestudied equivalently.We therefore propose the first-of-its-kind fMRI study of infants at-risk for autism at 12 and 24 months.Our proposed natural sleep fMRI experiments will be the first to map the neural systems activated by social,emotional and language information in the autistic, developmental^ delayed, and typically developing infant.Abnormal fMRI activation patterns will be identified that characterize and predict social emotional andlanguage behavioral deficits as measured in clinical assessment and diagnosis Core B. Behavioral deficitsin these three areas are among the first red flags signaling possible autism in the infant, and through ourstudies we will identify the first neurofunctional biomarkers of early development in autism. Identification ofthese neural functional biomarkers of early development in autism will enable us through collaboration withthe MRI Project 1, genetic Projects 3 and 4, the Treatment Core C and the Integrated Biostatistics Core D, toperform the first ever analyses that will establish relationships between brain function on the one hand andneuroanatomy, gene expression and genetic polymorphisms, clinical variables and treatment effectivenesson the other.
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