Goal-directed behaviour depends on keeping relevant information in mind (wo
rking memory) and irrelevant information out of mind (behavioural inhibitio
n or interference resolution). Prefrontal cortex is essential for working m
emory and for interference resolution, but it is unknown whether these two
mental abilities are mediated by common or distinct prefrontal regions. To
address this question, functional MRI was used to identify brain regions ac
tivated by separate manipulations of working memory load and interference w
ithin a single task (the Sternberg item recognition paradigm). Both load an
d interference manipulations were associated with performance decrements. S
ubjects were unaware of the interference manipulation. There was a high deg
ree of overlap between the regions activated by load and interference, whic
h included bilateral ventrolateral and dorsolateral prefrontal cortex, ante
rior insula, anterior cingulate and parietal cortex. Critically, no region
was activated exclusively by interference. Several regions within this comm
on network exhibited a brain-behaviour correlation across subjects for the
load or interference manipulation. Activation within the right middle front
al gyrus and left inferior frontal gyrus was correlated with the ability to
resolve interference efficiently, but not the ability to manage an increas
ed working memory load efficiently. Conversely, activation of the anterior
cingulate was correlated with load susceptibility, but was not correlated w
ith interference susceptibility. These findings suggest that, within the ci
rcuitry engaged by this task, some regions are more critically involved in
the resolution of interference whereas others are more involved in the reso
lution of an increase in load. The anterior cingulate was engaged to a grea
ter extent by the load than interference manipulation, suggesting that this
region, which is thought to be involved in detecting the need for greater
allocation of attentional resources, may be particularly implicated during
awareness of the need for cognitive control. In the present study, interfer
ence resolution did not involve recruitment of additional inhibitory circui
try, but was instead mediated by a subset of the neural system supporting w
orking memory.