No other period in human life matches the magnitude and astonishing increase in neural functional capacity as the transition from neonate to infant to toddler. Within a month or two following birth, the infant begins to smile and around first birthday begins to speak. Soon thereafter he coordinates speech and gesture in order to garner the attention of others. By the time he is two, he can speak in short sentences and has a rich repertoire of socio-emotional responding. Of all autism biology, the greatest mystery is what neural malfunction fails to provide this leap in social, 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 has attempted to discover the neurofunctional bases of this incredible achievement in typical infants or its profound failure in the autistic infant. We have performed ground-breaking pilot fMRI studies of typical and autistic toddlers mapping for the first 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 method of mapping neural function and malfunction allows testing to be done comparably regardless of developmental age or level of mental or behavioral ability;infants at all ages and levels of functioning can be studied 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 and language behavioral deficits as measured in clinical assessment and diagnosis Core B. Behavioral deficits in these three areas are among the first red flags signaling possible autism in the infant, and through our studies we will identify the first neurofunctional biomarkers of early development in autism. Identification of these neural functional biomarkers of early development in autism will enable us through collaboration with the MRI Project 1, genetic Projects 3 and 4, the Treatment Core C and the Integrated Biostatistics Core D, to perform the first ever analyses that will establish relationships between brain function on the one hand and neuroanatomy, gene expression and genetic polymorphisms, clinical variables and treatment effectiveness on the other.
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