title: Prenatal removal of frontal association cortex in the fetal rhesus monkey: anatomical and functional consequences in postnatal life.
abstract: Anatomical and behavioral consequences were examined following bilateral or unilateral resections of the presumptive dorsolateral prefrontal cortex in 4 rhesus monkey fetuses at E102 (102nd embryonic day), E104, E106 and E119, with subsequent replacement in utero and delivery at later stages of development. Unoperated monkeys of appropriate pre- and postnatal ages served as controls for certain features of morphogenesis and tectogenesis. Monkeys given comparable unilateral or bilateral lesions at selected postnatal ages were used as controls for the behavioral effects of prenatal resection as well as for neuropathological examination. The behavioral evaluation provided evidence for extraordinary preservation of function after frontal cortical resection in the prenatal period. During the entire course of its postnatal development, a monkey that sustained bilateral resection as a fetus at E106 performed surprisingly well and clearly with the competence of unoperated monkeys of identical or older ages on tasks selective for dorsolateral prefrontal cortical function; it did not exhibit deficits characteristic of animals that have comparable or even smaller resections as juveniles or adults. Following either unilateral or bilateral resection prior to E106, ectopic sulci and gyri appeared in intact regions of the frontal lobe of each hemisphere, as well as in locations at a considerable distance from the lesions, such as the temporal and occipital lobes. The cytoarchitectonic characteristics of the cortex in these anomalous gyri were typical of adjacent cortex in the regions in which they appeared. Examination of the parvocellular subdivision of the mediodorsal thalamic nucleus yielded the novel finding that this principal source of essential projections to the dorsolateral prefrontal cortex contained a virtually normal number of neurons in postnatal monkeys, following unilateral or bilateral lesions performed at or before E106, and exhibited only a partial loss of neurons after surgery at E119. The same cells regularly degenerate following comparable resections in the postnatal period. The survival of these neurons in prenatally operated monkeys is unprecedented, and can be explained by several hypotheses, including the possibility that their axons become rerouted to their structures in the absence of their normal targets. The present results thus demonstrate that ablation of a circumscript area of the frontal cortex in a non-human primate a full two months before birth may leave the functions later to be subserved by that area unaffected. Such early surgical intervention results in significant alteration in the gross morphological characteristics of the cortex, and apparently induces a functionally compensatory reorganization of thalamocortical connections. Similar principles may account for sparing of function following early damage to the human brain.
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001245:Association Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology; D002452:Cell Count; D002454:Cell Differentiation; D004193:Discrimination Learning / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000502:physiology*; D005865:Gestational Age; D000882:Haplorhini; D007858:Learning / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000166:cytology; D011247:Pregnancy; D011612:Psychosurgery; D012193:Reversal Learning / Q000502:physiology; D013028:Space Perception / Q000502:physiology; D013687:Telencephalon / Q000166:cytology; D013788:Thalamus / Q000166:cytology