The long-range objective of the proposed research is to elucidate basic principles and mechanisms governing the prenatal and postnatal development and plasticity of prefronatal association cortex in primates. The research is composed of four integral parts: (1) analysis of the outgrowth, synaptogenesis and organization of certain classes of prefrontal cortial connections during the course of prenatal and postnatal development; (2) assessment of the functional development of prefrontal cortex and related subcortical structures; (3) investigations of the structural and (4) functional plasticity which follows early injury to prefrontal cortex. The studies are conducted on rhesus monkeys because the expanse of association cortex in this species as well as its neuronal organization, protracted development and capacity for mediating complex behavior makes it an excellent animal model for the study of normal and pathological development of human neocortex. The project combines behavioral studies with a battery of advanced neurobiological methods (light and electron microscopic autoradiography, horseradish peroxidase and acetylcholinesterase histochemistry and (14C)-2-deoxyglucose mapping of the central nervous system). These techniques are used in conjunction with recently refined procedures that permit experimental manipulation of the primate fetal brain with subsequent return of the fetus to the uterus and its survival to and after term. Information from these studies will increase understanding of the development and modifiability of complex regions of the human brain and may lead to the discovery of means of prevention or treatment of cognitive disorders resulting from congential and neonatal brain injury.