MRI STUDIES OF EARLY BRAIN DEVELOPMENT IN AUTISM

University Of California, San Diego, La Jolla CA

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Abstract

Early brain overgrowth is a recently identified, but not yet directly measured, phenomenon in autism.[unreadable] Direct MRI measurement of the young autistic brain comes from five studies that found brain overgrowth at[unreadable] mean study ages of 2.7 to 3.9 yrs. Affected brain regions mediate higher-order social, emotional, language[unreadable] and cognitive functions that characterize autism. MRI studies of early brain growth in autism are absent.[unreadable] Indirect evidence of brain growth in autism comes from retrospective analyses of head[unreadable] circumference (HC). In the first study to examine the question, we reported that HC was normal average to[unreadable] slightly smaller than normal at birth in those who later manifested autism, but by about 12 months HC was[unreadable] abnormally large. Inferring brain growth rates from age-related changes in HC and placing that with the five[unreadable] MRI brain size studies of 2 to 4 year olds led us to the hypothesis that autism may involve a brief and agedelimited[unreadable] period of abnormal brain overgrowth during the first two years of life.[unreadable] According to the only two existent prospective studies of autism, 12 months is also approximately the[unreadable] first age at which autistic behavioral abnormalities first become detectable. The formation of neural circuitry[unreadable] is at its most exuberant and vulnerable stage during this period of development. Aberrant connectivity and[unreadable] neural dysfunction resulting from disruptions to this process may be key to the development of autistic[unreadable] behaviors. Thus, the first years of life in autism offer a unique chance to track the simultaneous emerging[unreadable] expression of the autistic anatomical and clinical phenotype and establish their relationship to each other and[unreadable] to underlying causal mechanisms, such as genes and genetic pathways that affect brain growth.[unreadable] We will identify early brain growth biomarkers in ASD by longitudinally MRI scanning infants at-risk[unreadable] for ASD, infants at-risk for developmental delay and typical infants at 12 and 24 months. We will obtain[unreadable] region-specific measures of volume, area, cortical thickness, fractional anisotropy and apparent diffusivity[unreadable] coefficient and developmental change values. Detailed anatomic maps of each region will be derived for[unreadable] each infant at each age. At age 36 months, a final best estimate diagnostic evaluation will identify which atrisk[unreadable] infants are ASD, DD or other. MRI results from these ASD and DD infants and typical infants will be[unreadable] statistically compared and early ASD brain growth abnormalities identified. Anatomical measures will be[unreadable] identified that characterize and predict the early developmental clinical phenotype of ASD that Cores B and[unreadable] C in collaboration with the Integrated Biostatistics Core D will identify. We will work with Project 4 and the[unreadable] Integrated Biostatistics Core D to use the brain growth biomarkers to discover overgrowth susceptibility[unreadable] genes and pathways. With Core D, we will identify separate clusters of distinctly different brain[unreadable] maldevelopment phenotypes among the ASD infants.[unreadable]