Dissociating the effects of Sternberg working memory demands in prefrontal cortex.

Earlier neuroimaging studies of working memory (WM) have demonstrated that dorsolateral prefrontal cortex (DLPFC) activity increases as maintenance and load demand increases. However, few studies have carefully disambiguated these two WM processes at the behavioral and physiological levels. The objective of the present functional resonance imaging (fMRI) study was to map within prefrontal cortex locales that are selectively load sensitive, delay sensitive, or both. We studied 18 right-handed normal subjects with fMRI at 3 Tesla during a block design version of the Sternberg task. WM load was manipulated by varying the memory set size (3, 5, or 8 letters). The effect of memory maintenance was examined by employing two time delays (1 s and 6 s) between the letter set and probe stimuli. The DLPFC was strongly activated in load manipulation, whereas activation as a function of delay was restricted to the left premotor regions and Broca's areas. Moreover, regions of prefrontal cortex on the right (BA 46) were found to be exclusively affected by load. These results suggest the possibility that top-down modulation of attention or cognitive control at encoding and/or decisionmaking may be mediated by these areas.