The use of cognitive subtraction to study the neural substrates of the main
tenance component of spatial working memory in humans relies upon the assum
ptions of the pure insertion of cognitive processes and a Linear transform
of neural activity to neuroimaging signal. Here, functional changes attribu
table to the memory requiring phase (referred to as the retention delay) of
a spatial working memory task were temporally discriminated from those att
ributable to other behavioral subcomponents within trials using an experime
ntal design that is argued to obviate these assumptions, as well as permit
a joint test of their validity. The hypothesis that the assumptions of cogn
itive subtraction (as applied to neuroimaging) hold in general was not supp
orted. Functional changes attributable to the retention delay were detected
in the dorsolateral prefrontal cortex as well as in other cortical regions
in a subset of the subjects, and in the right frontal eye field and right
superior parietal lobule of all subjects (n = 5). These results support mod
els in which these regions are involved in maintaining spatial representati
ons in humans. In addition, nearly all regions that evidenced such function
al changes during the retention delay also evidenced functional changes dur
ing behaviors that did not require spatial working memory. This result tend
s to dispute models which posit the existence of gross neuroanatomical regi
ons involved in solely mnemonic function. (C) 1999 Elsevier Science B.V. Al
l rights reserved.