Load response functions in the human spatial working memory circuit during location memory updating

Previous studies have emphasized that the dorsolateral prefrontal cortex is important for manipulating information in working memory, although activations in other frontal and parietal areas are commonly observed under the same conditions. We conducted an fMRI experiment to examine brain responses as a parametric function of memory updating, which is considered as an elemental process in working memory. In a variant spatial delayed-response task, human subjects performed updating operations over a 9-second delay period, during which they mentally transform the location of a memorized target in a 4 by 4 grid according to 3 to 12 instruction cues. Activity increased monotonically with increasing updating load in numerous cortical and subcortical regions including the rostrodorsal premotor (rdPM), lateral precentral sulcus, lateral prefrontal, posterior associative, striatal and cerebellar areas. The rdPM and superior parietal were particularly sensitive to the updating manipulation. There were several main findings. First, updating spatial working memory involved mostly the same cortical and subcortical regions that were activated during maintenance of spatial information. Second, the updating load response functions of regions in the spatial working memory circuit showed a strong linear component. However, none shows significant increases in activity from 9 to 12 updating operations. Third, activity in the right rdPM and anterior inferior frontal gyrus correlated positively with working memory performance in the high updating load condition. Our findings suggest that updating and maintenance of spatial information may share similar processes and that the rostrodorsal premotor cortex and anterior inferior frontal gyrus may be important for the success of tracking spatial information in working memory.