308 | VOL.1 NO.1 | 2006 | NATURE PROTOCOLS
The dorsal anterior midcingulate cortex (daMCC), dorsolateral
prefrontal cortex (DLPFC) and superior portions of parietal cor-
tex combine to form part of a cingulo-frontal-parietal cognitive/
attention network (CFP network)1–5. This brain network plays
critical roles in attention and cognitive processing, but group-ave-
raging techniques have generally been required to obtain sig-
nificant activation of these brain regions in functional neuro-
imaging studies—a fact that limits progress. For example, while
the Counting Stroop task has been useful in studying groups of
healthy volunteers and patients6, it has not been robust enough to
produce brain activation in single subjects. Although such group-
averaged tasks contribute greatly to our understanding of normal
human information processing, pathophysiology and drug effects,
they are not effective for use in clinical functional imaging contexts
since they cannot be used to distinguish a patient from a healthy
subject and/or other diagnostic groups. The MSIT was designed to
address these needs.
In developing the MSIT as a task to be used for assessing the
functional integrity of daMCC and DLPFC in neuropsychiatric
disorders7, we attempted to make it conform as closely as possible
to the characteristics of a hypothesized ideal functional neuroim-
aging-based diagnostic test. Specifically, we strove to ensure that it
possessed the following characteristics: (i) It must produce reliable
and robust activation of the cortical region(s) of interest (ROI)
within healthy individuals. (ii) It should be hypothesis driven (i.e.,
pre-existing evidence should support a mechanism explaining
why the task would be expected to recruit the ROI. (iii) It should
include collection of concomitant imaging and performance data
(reaction times and accuracy). (iv) Testing procedures must be
standardized. (v) The task instructions should be easy to learn and
retain so that the task can be performed by subjects with impaired
cognition (e.g., schizophrenia) and by subjects across a wide age
range (to enable developmental studies in children and studies of
elderly subjects). (vi) It should be of short duration, as children
and elderly subjects generally cannot tolerate protracted testing.
(vii) It should not be language specific (to facilitate cross-cultural
studies). (viii) Performance data should vary within a relatively
narrow range in healthy volunteers. (ix) Imaging and performance
data should be related. (x) Imaging and performance data should
show temporal stability (i.e., it should display sufficient test-retest
reliability to permit longitudinal and treatment studies). (xi)
Imaging and performance data should be sensitive to changes with
successful treatment. (xii) Results should be disorder specific.
Seeking first to use existing tasks to study the attention network
in attention-deficit hyperactivity disorder (ADHD) and schizo-
phrenia, we did pilot work using cognitive interference tasks (in
which the processing of one stimulus feature impedes the simul-
taneous processing of a second stimulus attribute). These would
include Stroop and Stroop-like tasks8–20, Eriksen Flanker-type
tasks21–23 and Simon effect task variants18. While full descrip-
tions of these cognitive interference tasks from which the MSIT
was derived are beyond the scope of this protocol, brief descrip-
tions are given here. The essence of the prototypical cognitive
interference task, the Color Stroop9,24, is that subjects take lon-
ger to name the color of the ink that color-words are written in
when the ink color and word are incongruent (e.g., the word ‘red’
written in blue ink) than when they do match (‘blue’ written in
blue ink) or when the word is a non-color word (‘house’ written
in blue ink). In the Eriksen Flanker Task25 subjects take longer to
identify a centrally located target letter (and make more errors)
when the target letter is flanked by incongruent distractor letters
(e.g., DDTDD) than when it is flanked by the same letter (e.g.,
The Multi-Source Interference Task: an fMRI task
that reliably activates the cingulo-frontal-parietal
George Bush1,2 & Lisa M Shin1,3
1Psychiatric Neuroscience Division, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Massachusetts General Hospital - East CNY-
2614, Building 149, Thirteenth Street, Charlestown, Massachusetts 02129, USA. 2MGH/MIT/HMS Athinoula A. Martinos Center for Functional and Structural Biomedical
Imaging, Massachusetts General Hospital, Massachusetts Institute of Technology & Harvard Medical School, Boston & Cambridge, Building 149, Thirteenth Street,
Charlestown, Massachusetts 02129, USA. 3Department of Psychology, Tufts University, Medford, Massachusetts 02155, USA. Correspondence should be addressed to G.B.
Published online 27 June 2006; doi: 10.1038/nprot.2006.48
In this protocol we describe how to perform the Multi-Source Interference Task (MSIT), a validated functional magnetic resonance
imaging (fMRI) task that reliably and robustly activates the cingulo-frontal-parietal cognitive/attention network (CFP network)
within individual subjects. The MSIT can be used to (i) identify the cognitive/attention network in normal volunteers and (ii)
test its integrity in people with neuropsychiatric disorders. It is simple to perform, can be completed in less than 15 min and
is not language specific, making it appropriate for children, adults and the elderly. Since its validation, over 100 adults have
performed the task. The MSIT produces a robust and temporally stable reaction time interference effect (range 200–350 ms), and
single runs of the MSIT have produced CFP network activation in approximately 95% of tested subjects. The robust, reliable and
temporally stable neuroimaging and performance data make the MSIT a useful task with which to study normal human cognition
and psychiatric pathophysiology.
© 2006 Nature Publishing Group http://www.nature.com/natureprotocols
NATURE PROTOCOLS | VOL.1 NO.1 | 2006 | 313
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