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J Neurosci. 2007 Mar 28;27(13):3429-38.

Functional coupling of human prefrontal and premotor areas during cognitive manipulation.

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  • 1Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.


Evidence indicates the involvement of the rostral part of the dorsal premotor cortex (pre-PMd) in executive processes during working memory tasks. However, it remains unclear what the executive function of pre-PMd is in relation to that of the dorsolateral prefrontal cortex (DLPFC) and how these two areas interact. Using functional magnetic resonance imaging (fMRI), brain activity was examined during a delayed-encoding recognition task. Fifteen subjects had prelearned several four-code standard sequences and super sequences (SUPs) consisting of a train of two standard sequences to form "chunks" in long-term memory. During fMRI, subjects remembered eight-code encoding stimuli presented as an SUP or two unlinked standard sequences (2STs). A memory probe prompted the subjects to recognize codes across two chunks (ACROSS) or within a single chunk. A 2 x 2 factorial design was used to test two types of working memory manipulation: (1) a reductive operation selecting codes from chunks ("segmenting") and (2) a synthetic operation converting unlinked codes into a sequence ("binding"). Response time data supported the behavioral effects of each operation. Event-related fMRI showed that the "segmenting operation" activated the DLPFC bilaterally, whereas the "binding operation" enhanced the left pre-PMd activity. Activity in the ventrolateral prefrontal cortex suggested its involvement in the retrieval of task-relevant information from long-term memory. Furthermore, effective connectivity analysis indicated that the left pre-PMd and ipsilateral DLPFC interacted specifically during the ACROSS recognition of 2STs, the condition that involved both operations. We propose specific neural substrates for working memory manipulation: the DLPFC for segmenting/attentional selection and the pre-PMd for binding/sequencing. The functional coupling between the DLPFC and pre-PMd appears to play a role in combining these distinct operations.

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