Prenatal cocaine exposure (CE) has been a major public health concern since the epidemic of use that began in the 1980s. A number of studies have examined the physical, neurodevelopmental, and psychosocial effects of parental cocaine abuse and prenatal cocaine exposure in infants and young children but provided limited understanding of the neurobiological basis and neurodevelopmental effects. Recent advances in neuroimaging methods have made it possible to examine directly and noninvasively the functional neuroanatomy and connectivity, making them ideally suited for investigating the neurobiology and developmental effects of prenatal CE. The overall goal of this project is to apply MRI based neuroimaging methods, in conjunction with neurobehavioral testing, to study the neurodevelopmental effects of prenatal CE during adolescence and to elucidate neurobiological basis of the effect of prenatal CE. The proposed imaging study will focus on arousal and attention regulation, the neuropsycological functions which have been implicated most reliably in most studies of prenatal CE, the brain circuitry involved in these functions, and developmental effects on these brain circuitry during puberty, which, as a period of rapid reorganization, is ideal for the assessment of delays or divergences in development as a result of prenatal CE. We hypothesize that (1) using MRI, developmental change in structure and function will be evident in youth assessed over a 6 year period from 12 to 18 with measures of brain activity, neuroanatomic connectivity, and functional connectivity; (2) adolescents with prenatal cocaine exposure will exhibit deficit in arousal and attention regulation when compared to SES-matched controls, and these deficits will be more evident in situations involving stress than at """"""""baseline"""""""" and will be measurable using MRI techniques as well as behavioral assessment of functioning; and (3)There will be correlations between MRI and behavioral measures. To test these hypotheses, the specific aims are (1) to compare functional anatomy of CE subjects and SES- and age matched controls at 3 age levels, 12, 15 and 18-years, to identify the patterns of developmental characteristic of each group; (2) to assess possible alterations in the neuroanatomic connectivity in and between areas serving the function of arousal and attention regulation in these groups using diffusion tensor imaging; (3) to assess functional connectivity in neural circuits in these groups; and (4) to assess behavior and adaptive functioning in these groups and correlate these outcomes with MRI findings. We believe the studies proposed in this project, the first to apply neuroimaging methods to this population, will allow us to ascertain possible alterations in the brain as a result of prenatal CE and measure any developmental effects on the brain during puberty.
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