R (2005): Specific cerebral networks for maintenance and response organization within working memory as evidenced by the double delay=double response paradigm. Cereb Cortex 15:1064–1074

Most of the working memory (WM) tasks used in functional imaging studies are based on the principle of the delayed response in which both the storage and the response organization are present during the delay period. It is therefore difficult to isolate activation specific to the storage function from that specific to the organization of the response. To determine the specific neural networks associated with these two WM operations, we performed a functional MRI study in healthy subjects using a new paradigm, ‘the double delay/double response ’ tasks. This paradigm isolates maintenance from response organization by dividing the delay into two separate parts, the first being dedicated to memory, while the second includes response organization. Activation within the dorsolateral prefrontal cortex (DLPFC) followed a relative hemi-spheric dissociation: activation related to maintenance was pre-dominant in the right DLPFC but was only detected when the load exceeded three items. Activation related to response organization was predominant in the left DLPFC, regardless of whether this response was based on information held in WM (‘memory guided’) or was independent of WM (‘visually-guided’). These results suggest that activation of the DLPFC, should be interpreted in terms of executive processing for both maintenance and response organization