PERSEVERATION AND STRATEGY IN A NOVEL SPATIAL SELF-ORDERED SEQUENCINGTASK FOR NONHUMAN-PRIMATES - EFFECTS OF EXCITOTOXIC LESIONS AND DOPAMINE DEPLETIONS OF THE PREFRONTAL CORTEX

Damage to the prefrontal cortex disrupts the performance of self-order ed sequencing tasks, although the precise mechanisms by which this eff ect occurs is unclear. Active working memory, inhibitory control, and the ability to generate and perform a sequence of responses are all pu tative cognitive abilities that may be responsible for the impaired pe rformance that results from disruption of prefrontal processing. In ad dition, the neurochemical substrates underlying prefrontal cognitive f unction are not well understood, although active working memory appear s to depend upon an intact mesocortical dopamine system. The present e xperiments were therefore designed to evaluate explicitly the contribu tion of each of these abilities to successful performance of a novel s patial self-ordered sequencing task and to examine the contribution of the prefrontal cortex and its dopamine innervation to each ability in turn. Excitotoxic lesions of the prefrontal cortex of the common marm oset profoundly impaired the performance of the self-ordered sequencin g task and induced robust perseverative responding. Task manipulations that precluded perseveration ameliorated the effect of this lesion an d revealed that the ability to generate and perform sequences of respo nses was unaffected by excitotoxic damage to prefrontal cortex. In con trast, large dopamine and noradrenaline depletions within the same are as of prefrontal cortex had no effect on any aspect of the self-ordere d task but did impair the acquisition of an active working memory task , spatial delayed response, to the same degree as the excitotoxic lesi on. These results demonstrate that a lesion of the ascending monoamine projections to the prefrontal cortex is not always synonymous with a lesion of the prefrontal cortex itself and thereby challenge existing concepts concerning the neuromodulation of prefrontal cognitive functi on.