Evidence for multiple manipulation processes in prefrontal cortex.

The prefrontal cortex (PFC) is known to subserve working memory (WM) processes. Brain imaging studies of WM using delayed response tasks (DRTs) have shown memory-load-dependent activation increases in dorsal prefrontal cortex (PFC) regions. These activation increases are believed to reflect manipulation of to-be-remembered information in the service of memory-consolidation. This speculation has been based on observations of similar activation increases in tasks that overtly require manipulation by instructing participants to reorder to-be-remembered list items. In this study, we tested the assumption of functional equivalence between these two types of WM tasks. Participants performed a DRT under two conditions with memory loads ranging from 3 to 6 letters. In an "item-order" condition, participants were required to remember letters in the order in which they were presented. In a "reordering" condition, participants were required to remember the letters in alphabetical order. Load-related activation increases were observed during the encoding and maintenance periods of the order maintenance condition, whereas load-related activation decreases were observed in the same periods of the reordering condition. These results suggest that (1) the neural substrates associated with long-list retention and those associated with reordering are not equivalent, (2) cognitive processes associated with long-list retention may be more closely approximated by item-order maintenance than by reordering, and (3) multiple forms of WM manipulation are dissociable on the basis of fMRI data.