Maturation of prefrontal cortex in the monkey revealed by local reversible cryogenic depression

Abstract

THE emergence of increasingly complex cognitive functions with age is widely assumed to reflect in part the maturation of connections within the central nervous system, but the neural bases of cognitive development have resisted identification. There is some evidence to indicate that the dorsolateral prefrontal association cortex in monkeys acquires its adult functional capacities over a protracted span of postnatal development^1–3. Most of this evidence, however, has come from studies involving surgical ablation. The study of cerebral development in brain-damaged subjects is complicated by anterograde and retrograde degenerative changes, as well as by the possibility of compensatory neural reorganisation which could occur during the weeks or months between surgical ablation and assessment of behavioural performance⁴. It is now possible to study the functions of specific brain sites without producing permanent brain damage by localised cortical cooling, a method which allows reversible inactivation of restricted regions of cortex in otherwise normal animals. The latter are able to serve as their own controls before and after the episodes of cortical hypothermia^5–7. This method has previously been used only in research on mature animals. In this study, local hypothermia was produced for the first time in the dorsolateral prefrontal cortex of young, developing rhesus monkeys during repeated assessment of their performance on a delayed-response task. Such performance in adult monkeys is known to be dependent on the integrity of that region⁸. Our findings provide direct evidence that part of the dorsolateral prefrontal association cortex does not become functionally mature until at least 34–36 month of age, that is, close to sexual maturity in this species.