Because of cocaine's effect on developing monoaminergic systems, prenatal cocaine-exposure may interfere with the developmental ontogeny of children's abilities to regulate states of arousal and attention, thereby altering the development of prefrontal cortical executive functions. The present proposal seeks to extend promising preliminary findings regarding cortical functioning in prenatally cocaine exposed school-aged children participating in event related potential (ERP) studies. Subjects participating in these preliminary studies are members of cohort of 369 children followed longitudinally since birth (RO1 DA-06025) with biyeady visits in which we have described a continuum of developmental impairment among prenatally cocaine-exposed children that includes emotional lability, impaired visuospatial processing and visual motor integration, impulsivity and difficulty inhibiting prepotent responses. The cohort is currently participating in an ongoing 7 to 11 year follow-up with repeated assessments of, among other domains, attention regulation and aspects of executive functioning. In the preliminary ERP studies that are the basis of the present proposal, 29 prenatally prenatally cocaine-exposed and non-cocaine-exposed 7 to 9 year old children responded to a standard Stroop paradigm and a familiarization paradigm. Effects across both experiments were noted in the region of the initial positive peak (P1), the following large negative peak (N1) and the later positive peak (P2). In the Stroop paradigm, cocaine exposed children generated longer latency and prolonged ERP components while the control children produced faster and briefer responses. In the familiarization paradigm, results suggest that cocaine exposed children utilize more cortex to discriminate between repeated presentations of the same stimuli compared to non-cocaine exposed children. Taken together, these findings indicate that early exposure to cocaine may inhibit the specialization and streamlining of brain region involvement during cognitive processing such that task processing is slower to begin, requires more diverse cortical involvement, and requires more time to complete. Based on these findings, we propose to use ERP methods to assess with repeated visits at 11,12, & 13 years the 369 children participating in our longitudinal cohort using three stimulus response experiments, the Stroop, a familiar-novel words paradigm, and a P300 traditional """"""""odd-ball"""""""" paradigm. Research utilizing ERP methodology in children has demonstrated its potential in studying frontal maturation, and thus it may provide additional information necessary for clarifying the general and specific effects of prenatal cocaine exposure on cortical functioning and the developmental course of cognitive functions. Such information may then lead to better definition and treatment of these developmental problems.
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