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, 96 (13), 7514-9

The Neural Substrate and Temporal Dynamics of Interference Effects in Working Memory as Revealed by Event-Related Functional MRI

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The Neural Substrate and Temporal Dynamics of Interference Effects in Working Memory as Revealed by Event-Related Functional MRI

M D'Esposito et al. Proc Natl Acad Sci U S A.

Abstract

Research on the prefrontal cortex (PFC) of monkeys and humans indicates that this region supports a heterogeneous repertoire of mental processes that contribute to many complex behaviors, such as working memory. Anatomical evidence for some of these processes derives from functional neuroimaging experiments using blocked experimental designs, which average signal across all components of many trials and therefore cannot dissociate distinct processes with different time courses. Using event-related functional MRI, we were able to isolate temporally the neural correlates of processes contributing to the target presentation, delay, and probe portions of an item-recognition 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 that did not match a target item from either the present or the two previous trials. There was no difference between the two trial types in target presentation (i.e., encoding) or delay-period (i.e., active maintenance) PFC activation, but there was significantly greater activation for Recent Negatives than Nonrecent Negative activation associated with the probe period within left ventrolateral PFC. These findings characterize spatially and temporally a proactive interference effect that may reflect the operation of a PFC-mediated response-inhibition mechanism that contributes to working memory performance.

Figures

Figure 1
Figure 1
Schematic illustration of the item-recognition task. Each trial lasted 9.5 sec followed by a 14.4-sec intertrial interval. Target items were presented for 950 msec followed by a 7,050-msec delay period. This interval was followed by a probe letter for 1,500 msec that either was recently presented (Recent trial) or was not recently presented (Nonrecent trial). Note that, in the Recent Negative trial, the probe letter “P” is not in the target set of that trial but that it is in the target set of the two previous trials. The arrows along the time line represent the placement of independent variables positioned to detect variance in the fMRI signal associated with target presentation, delay period, and probe portions of the trial, respectively.
Figure 2
Figure 2
Pattern of activation with each of the task components. Shown are axial slices encompassing the ventral PFC ROI (white circles) in a representative subject (WB). Significantly greater activation (relative to the intertrial interval) is seen during the Recent Negative trials as compared with the Nonrecent Negative trials during the Probe period and not during the presentation of the Target or during the Delay period.
Figure 3
Figure 3
Pattern of activation within the probe period of the task. Shown are axial slices encompassing the ventral PFC ROI (white circles) in each subject showing activation in the Recent Negative and Nonrecent Negative trials.
Figure 4
Figure 4
Trial averaged time series. Shown are the trial-averaged time series data for a representative subject extracted from voxels demonstrating a main effect for the Probe period across both Recent Negative and Nonrecent Negative trials. Activity in the two conditions differed statistically only during the Probe portion of the task (see arrow).

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