The functional neuroanatomy of classic delayed response tasks in humans and the limitations of cross-method convergence in prefrontal function.

Three classic delay tasks: spatial delayed response, delayed spatial alternation and delayed object-alternation are prototypical experimental paradigms for mapping the functional neuroanatomy of prefrontal cortex in animals. These tasks have been applied in human lesion studies, yet there have been very few studies investigating their functional neuroanatomy in healthy human subjects. We used functional magnetic resonance imaging to investigate the functional neuroanatomy of these classic paradigms (and a fourth: object delayed response) in a single sample of healthy human participants. Consistent with previous animal, human lesion, and functional neuroimaging studies, activity was observed in prefrontal and posterior parietal cortices across all three delay tasks. Task-specific activations, however, were not entirely consistent with predictions drawn from animal lesion studies. For example, delayed object-alternation activated dorsolateral prefrontal cortex, a region not generally implicated in animal lesion reports. Spatial delayed response, classically associated with the dorsolateral prefrontal cortex, did not activate this region; it rather activated posterior premotor cortices involved in response preparation, as did spatial alternation. All three tasks activated the frontopolar cortex, a region not considered crucial in animal research but associated with manipulation of internally generated information in recent human research. While cross-method convergence may be attained for lower level perceptual or motor tasks, the results of this study caution against the assumption that lesion-specific effects in animals generalize to human prefrontal cortex function.