The neural substrate and temporal dynamics of interference effects in working memory as revealed by event-related functional MRI

Research on the prefrontal cortex (PFC) of monkey and humans indicates that this region supports a heterogeneous repertoire of mental processes that c ontribute to many complex behaviors, such as working memory. Anatomical evi dence for some of these processes derives from functional neuroimaging expe riments using blocked experimental designs, which average signal across all components of manly trials and therefore cannot dissociate distinct proces ses with different time courses. Using event-related functional MRI, we wer e able to isolate temporally the neural correlates of processes contributin g to the target presentation, delay, and probe portions of an item-recognit ion task. Two types of trials were of greatest interest: those with Recent Negative; probes that matched an item from the target set of the previous, but not the present, two trials, and those with Nonrecent Negative probes t hat did not match a target item from either the present or the two previous trials. There Has no difference between the tno trial types in target pres entation (i.e, encoding) or delay-period (i.e,, active maintenance) PFC act ivation, but there was significantly greater activation for Recent Negative s than Nonrecent Negative activation associated with the probe period withi n left ventrolateral PFC, These findings characterize spatially and tempora lly a proactive interference effect that may reflect the operation of a PFC -mediated response-inhibition mechanism that contributes to working memory performance.