Through this competing continuation application for an RSDA (K02) award, I seek to extend and deepen a line of work on arousal and attention regulation in prenatally cocaine-exposed children that I have developed with an initial five years of support. In these previous five years, I have developed my line of work along models of neurobehaviorail teratology while continuing a thematic focus dating from earlier in my research career on brain-behavior relations and the regulation of states of arousal. My proposal for the next five years makes full use of the interdisciplinary collaborative opportunities within my own department (the Yale Child Study Center) and with two collaborators in other institutions. I propose to extend my focus on mechanisms of arousal regulation with both new conceptual and methodologic/applied emphases on the neurobiology, neurophysiology, and neuropsychology of arousal regulation in preschool and school age children exposed to biological risks (e.g., prenatal cocaine exposure) and psychosocial adversity. I propose three areas of career development: (1 ) To extend my knowledge regarding neurobiological models of arousal regulation with specific attention to corticostriatal systems and the interface with neuropsychological approaches to prefrontal cortical function, (2) To apply neurophysiologic methods to the study of arousal regulation (e.g., the fear or emotion-potentiated startle response); and (3) To extend my understanding of the neuropsychological assessment of arousal and attention regulation in preschool and school age children. The accompanying research plan is based on an ongoing R01 (DA 06025) now in the seventh year of NIDA funding. The ongoing study examines relations among prenatal cocaine exposure, postnatal environmental instability, and the cognitive and social development of infants and children from birth through 8 years of age. The developmental domains of particular focus are the regulation of arousal and attention. The proposed cohort for study is 442 children (254 prenatally cocaine-exposed and 188 non-cocaine-exposed) who now range in age from 3.5 to 7 years. Children will be seen biyearly between 4 and 8 years with repeated assessments in the following domains: a) arousal regulation operationalized behaviorally as state and emotional reactivity and neurophysiologically as the startle response and heart rate variability; (b) attention regulation operationalized as the ability to sustain attention, identify stimuli, and inhibit responses; (c) aspects of executive functioning (in particular reflective of prefrontal cortex functioning); (d) cognitive function, (e) adaptive and maladaptive behavior, (f) school performance; (9) social adjustment, and (h) the incidence of childhood psychiatric disorders of attention, anxiety, and conduct. Early disruption of the developmental ontogeny of arousal and attentional regulatory capacities may have effects that extend well into the school-aged years and alter the normal trajectory of cognitive and social-emotional development.
