Neuropsychologia 44 (2006) 2836–2845

How default is the default mode of brain function?

Further evidence from intrinsic BOLD signal fluctuations
Peter Fransson ∗
MR Research Center, Cognitive Neurophysiology, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
Received 2 March 2006; received in revised form 31 May 2006; accepted 2 June 2006
Available online 1 August 2006

Abstract
The default mode of brain function hypothesis and the presence of spontaneous intrinsic low-frequency signal fluctuations during rest have
recently attracted attention in the neuroscience community. In this study we asked two questions: First, is it possible to attenuate intrinsic activity
in the self-referential, default mode of brain function by directing the brains resources to a goal-oriented and attention-demanding task? Second,
what effect does a sustained attention-demanding overt task performance have on the two intrinsically active networks in the brain, those being the
task-negative, default-mode and the anticorrelated, task-positive network? We used functional magnetic resonance imaging to monitor spontaneous
intrinsic activity during rest and sustained performance of a sequential two-back working memory task. We compared intrinsic activity during
rest and the two-back task to the signal increases and decreases observed in an epoch-related version of the working memory task. Our results
show that spontaneous intrinsic activity in the default-mode network is not extinguished but rather attenuated during performance of the working
memory task. Moreover, we show that the intrinsic activity in the task-positive network is reorganized in response to the working memory task. The
results presented here complements earlier work that have shown that task-induced signal deactivations in the default-mode regions is modulated
by cognitive load to also show that intrinsic, spontaneous signal fluctuations in the default-mode regions persist and reorganize in response to
changes in external work load.
© 2006 Elsevier Ltd. All rights reserved.

Keywords: fMRI; Spontaneous activity; Resting brain; Default mode of brain function; Working memory

1. Introduction signal fluctuations (Biswal, Yetkin, Haughton, & Hyde, 1995)

The default mode of brain function hypothesis is based
on PET and fMRI observations of task-independent signal
decreases of brain activity during attention-demanding cognitive
tasks (Binder et al., 1999; Gusnard & Raichle, 2001; Raichle
et al., 2001; Mazoyer et al., 2001; Shulman et al., 1997). Con-
sequently, the default mode of brain function theory posits that
these brain regions exhibit an increased level of activity during
resting-state and that they are engaged in spontaneous, self-
referential mental activity when there are no external demands
on our attention (Gusnard, Akbudak, Shulman, & Raichle,
2001). Other studies have linked the presence of low-frequency
(<0.1 Hz) BOLD (blood oxygenation level dependent) fMRI
∗ Present address: MR Research Center, N8, Department of Clinical Neuro-
science, Karolinska University Hospital, SE 171 76 Stockholm, Sweden.
Tel.: +46 8 5177 6113; fax: +46 8 5177 3266.
E-mail address: Peter.Fransson@ki.se.
during resting-state to the default-mode brain regions (Fox et
al., 2005; Fransson, 2005; Greicius, Krasnow, Reiss, & Menon,
2003; Waites, Stanislavsky, Abbott, & Jackson, 2005). In
addition, spontaneous, low-frequency BOLD signals have been
associated to the presence of correlated EEG activity in the
resting state (Laufs et al., 2003). This implies that default-mode
brain regions collectively show a decrease in activity for
attention-demanding overt tasks, but also that there exists an
intrinsic, functional connectivity that is mediated through spon-
taneous low-frequency BOLD signal fluctuations during rest for
the network of brain regions that support the default mode. Apart
from the default-mode network, recent studies have shown
that there exist at least five different resting state networks in
the brain, where several of these encompass primary sensory
areas (Beckmann, DeLuca, Devlin, & Smith, 2005; De Luca,
Beckmann, De Stefano, Matthews, & Smith, 2005). Moreover,
two recent studies have shown that there seems to exist two
diametrically opposed functional networks during rest, where

0028-3932/$ – see front matter © 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.neuropsychologia.2006.06.017
 P. Fransson / Neuropsychologia 44 (2006) 2836–2845
one network consists of regions routinely exhibiting task-related
deactivations (task-negative/default-mode network) and an anti-
correlated, i.e. negatively correlated, network of brain regions
that routinely exhibits task-related (task-positive) activations
(Fox et al., 2005; Fransson, 2005). In other words, whenever
the level of activity, due to spontaneous signal fluctuations
during rest, increase in the default-mode regions, it decreases in
the task-positive network of brain regions and vice versa. The
network of brain regions that in the context of spontaneous,
intrinsic signal fluctuations during rest is described as the task-
positive network largely overlap with the set of brain regions
named the dorsal attention network and previously attributed
to goal-oriented and top-down modulated control of attention
in studies that have used conventional epoch-related and/or
event-related paradigm designs (Corbetta & Shulman, 2002).
The question of attenuation of resting-state default-mode
activity has previously only been addressed for very low
demands of external attention by Greicius and Menon (2004)
or by using epoch-related fMRI paradigm designs (McKiernan,
Kaufman, Kucera-Thompson, & Binder, 2003; McKiernan,
D’Angelo, Kaufman, & Binder, 2006). Greicius and Menon
showed in their study that the default-mode intrinsic activity
was only very little affected by the subjects passively attend-
ing to simple sensory stimuli such as a visual checkerboard
or a white noise burst delivered during 30 s epochs interleaved
with intervals of rest. Using an epoch-related design of an audi-
tory discrimination task, McKiernan and colleagues showed that
task-induced deactivations in several of the default-mode regions
varied parametrically as a function of task difficulty (McKiernan
et al., 2003). Moreover, in a recent follow-up study the same
group showed that the frequency of so-called TUTs (task un-
related thoughts) co-varied with the magnitude of task-induced
deactivation in four left hemisphere regions implicated in self-
referential thought (McKiernan et al., 2006). However, to the
authors’ knowledge, no study so far has studied the impact of
cognitive load on intrinsic brain activity, i.e. spontaneous, slow-
frequency signal fluctuations (Fox et al., 2005; Fransson, 2005;
Greicius et al., 2003).
In this study we addressed this issue by focusing on the fol-
lowing two questions: To what extent is the default mode of
brain function really a default mode or stated differently, is it
possible to attenuate or possibly even completely suspend the
intrinsic and self-referential default mode of brain function by
directing the brain’s computational and cognitive resources to
an external, goal-oriented and highly attention-demanding task?
In other words, the present study was aimed at investigating
whether we could replicate previous studies (McKiernan et al.,
2003, 2006) that showed task-induced deactivations of default-
mode activity but here using a different methodology (intrinsic
activity) and a different task. Second, we were interested in what
effect an externally driven, goal-oriented task might have on the
mutual dynamics of the two intrinsically organized functional
networks. In particular, we were interested whether the spon-
taneous, task-unrelated signal fluctuations in the task-positive
network would be reorganized due to the fact that the involved
brain regions typically exhibit task-related, non-intrinsical sig-
nal increases in epoch-related neuroimaging experiments. These
2837
two questions were addressed by investigating the behaviour
of spontaneous, low-frequency BOLD fMRI signal intensity
changes during sustained periods (10 min) of rest and during
performance of a sustained version of a verbal, sequential two-
back working memory (WM) task—a task that has previously
been used extensively in cognitive psychology and neuroimag-
ing studies and known to heavily tax the brains’ attentional and
computational resources (Cabeza & Nyberg, 2000; Wager &
Smith, 2003). In contrast to previous studies (McKiernan et
al., 2003, 2006; Greicius & Menon, 2004), we chose to use
a sustained rather than an epoch-related paradigm structure for
the working memory task. The advantage of using a sustained
paradigm is that we maintain a high level of outwardly directed
attention and high computational load during a prolonged period
of time, thereby avoiding the potential problem of confounding
the spontaneous low-frequency fluctuations of interest (<0.1 Hz)
with the periodic fMRI signal intensity time courses typically
evoked by epoch-related designs. From a cognitive work load
perspective, we were interested in intrinsic default-mode func-
tionality in two completely opposed baseline conditions. In the
rest condition, our aim was to maximize the potential for spon-
taneous thought to occur during scanning. On the other hand, in
the sequential two-back task we strove to minimize the poten-
tial for spontaneous thought by burdening the subjects with a
demanding working memory task. The degree to which spon-
taneous events or so-called TUTs (“task unrelated thoughts”,
McKiernan et al., 2003, 2006) such as inner speech, imagery,
episodic memory, planning for the future, and task-unrelated
attention occurred during scanning was individually rated by
each subject immediately after each scanning session.
The spatial and temporal characteristics of intrinsic, low-
frequency BOLD signal fluctuations during sustained periods of
rest and performance of the WM task were assessed by means
of three complementary analyses. (i) Functional connectivity
within and between the two networks was calculated using a
ROI-based correlational analysis approach for both rest and the
WM task. Differences in correlational, intrinsic activity during
rest and the WM task were assessed by two-sample t-tests. (ii)
Estimates of the amount of intrinsic signal fluctuation within
the default-mode network were compared between the two con-
ditions by computing power spectral densities in the frequency
interval of interest (0.012–0.15 Hz). (iii) We adopted the strategy
outlined by Greicius and colleagues (Greicius et al., 2003, 2004)
of decomposing the four-dimensional fMRI dataset into separate
components using the independent component analysis decom-
position technique (Beckmann & Smith, 2004). A comparative
analysis across conditions were carried out using the goodness-
of-fit measure described in Greicius, Srivastava, Reiss, & Menon
(2004) employing a default-mode brain template constructed
from an independent cohort of subjects (Fransson, 2005).
2. Materials and methods
2.1. Subjects and tasks
Fourteen normal subjects (five males, ages 22–41, mean 30.2 years, S.D.
6.4 years) participated in the study. All subjects were right-handed as judged
2838 P. Fransson / Neuropsychologia 44 (2006) 2836–2845
by the Edinburgh Handedness Inventory. All MR examinations were carried
out according to the ethical guidelines and declarations of the Declaration of
Helsinki 1975. This study was approved by the local ethics committee at the
Karolinska University Hospital. Subjects underwent two 10 min scans during
which they performed a resting-state, low-level baseline task (eyes open, visual
fixation on a hair-cross-centered in the screen) and a sequential two-back verbal
working memory task. For the two-back WM task, stimulus items in the form of
written words in Swedish were presented visually. The subjects were instructed
to answer affirmatively if the presented word was identical to the word presented
two words back in the list, otherwise negatively. Further, the subjects were
asked to respond to each word by pressing one of two buttons mounted on
a glove which the subjects wore on their right hand. All responses and their
timing were recorded automatically. During the 10 min scan, including an extra
4 dummy scans in the beginning, 244 words were continuously presented with
an interstimulus interval of 2500 ms. Our choice of using a very short inter-
stimulus interval between consecutive trial presentations served two purposes.
First, a short inter-stimulus interval minimizes the time available for the subject
to engage in task-unrelated thoughts (TUTs) and hence causes a continuous and
elevated level of cognitive work load. Second, it has previously been shown that
when events of the same kind are presented employing a very short inter-stimuli
interval as used here, they will in the affected brain regions cause a fMRI signal
that, due to the sluggishness of the hemodynamic response, is characterized by
a sustained signal increase that lasts for the total duration of the experiment
with only a small event-related BOLD response due to the individual trials
(Fransson, Krueger, Merboldt, & Frahm, 1998). Although the rapid presentation
of the individual WM trials will cause a small trial-evoked “ripple” in the fMRI
signal profile that is superimposed on the elevated and sustained BOLD signal,
these trial-evoked signal changes emerge at a frequency of 0.4 Hz, which is well
outside the frequency range of the spontaneous and intrinsic signal changes that
are the focus of interest in this study. Hence, we test for the presence of low-
frequency, spontaneous signal fluctuations that are linearly superimposed on the
sustained and elevated fMRI signal intensity baseline level during the WM task
(Fox, Snyder, Zacks, & Raichle, 2006). Additionally, in an epoch version of
the sequential two-back task, subjects were presented with a total of 60 words
divided up into five lists of 12 words each (30 s) separated with periods of
visual fixation (20 s). Finally, the subjects underwent two event-related pattern
recognition tasks which were not analyzed for this study and will not be discussed
further. The presentation order of all fMRI runs were counter balanced across
subjects. In total, each subject participated in five fMRI runs. Subjects were also
instructed immediately after the scanning sessions to rate their subjective level
of spontaneous, task-unrelated thoughts occurring during resting state and the
WM task.
2.2. Image acquisition
A 1.5 T General Electric Twinspeed Signa Horizon MR scanner was used to
acquire both functional and anatomical MR image data sets. High-resolutional,
structural T1-weighted images were acquired in a coronal orientation employ-
ing a 3D-SPGR (spoiled gradient recalled) sequence (TR/TE = 24/6 ms, flip
angle = 35◦ ) with a voxel size of 0.9 mm × 1.5 mm × 0.9 mm. A gradient-echo
echo-planar imaging (EPI) sequence was used to monitor BOLD fMRI sig-
nal changes during resting state, sustained and epoch versions of the sequen-
tial two-back task (TR/TE = 2000/40 ms, flip angle = 80◦ , 64 × 64 matrix size,
FOV = 220 mm × 220 mm, 29 slices, slice thickness 4–4.5 mm). For the rest and
the sustained WM task, 300 EPI volumes were acquired (10 min) whereas 135
EPI volumes were acquired for the epoch version of the two-back task (4 min
and 40 s). An additional four (dummy) EPI volumes were acquired before the
start of each session to account of T1-equilibrium effects.
2.3. Data analysis
The SPM2 (statistical parametrical mapping) software package (Wellcome
Dept. of Imaging Neurosci., Friston et al., 1995) was used for image pre-
processing and statistical analysis. Correction for subject movement was done by
realigning all EPI images to the first image in the first series. The T1-weighted
high-resolution image volume was co-registered to the mean EPI image and
spatially normalized to the approximate Talairach space (Talairach & Tournoux,
1988) as defined by the MNI (Montreal Neurological Institute) EPI template
in SPM2. The normalized image volumes were resampled to a voxel size of
3 mm × 3 mm × 3 mm. As a final step, EPI images were spatially smoothed
using an isotrophic Gaussian filter (12-mm FWHM). For the epoch version of
the WM task, epoch-related signal changes pertaining to activations and deac-
tivations with respect to rest were modelled using the general linear model as
implemented in SPM2 using the canonical hemodynamic response function.
2.4. Correlation techniques
For the ROI-based correlation analysis all image data was high-pass filtered
with a cut-off frequency of 0.012 Hz. A single spherical ROI (radius 10 mm)
positioned in the PCC/precuneus area [0, −52, 30] was used to extract the mean
BOLD signal intensity. Before inserting the ROI signal time course as a regres-
sor in a general linear model, the signal intensity time course was band pass
filtered (pass band 0.012–0.1 Hz) using a phase-insensitive filter and the mean
global brain signal was subtracted. Additionally, six parameters of no interest
pertaining to estimates of rigid body motion during scanning were inserted into
the model to account for residual movement-related variance. Subsequently,
contrast images constituting subject-specific intrinsic correlation and anticor-
relation (i.e. negative correlation) with the selected ROI were entered into a
second level model (one sample t-test) for each contrast, yielding a random
effects model (Holmes & Friston, 1998). The resulting SPM[T] maps of acti-
vated voxels were thresholded at p < 0.05, corrected for multiple comparisons
using the FDR-criterion (Genovese et al., 2002). We limited the ROI-based cor-
relation analysis to include only a single brain region for two reasons. (i) We
have in a previous, independent study used the same precuneus/PCC seed region
to show intrinsic correlation and anticorrelation during resting-state (Fransson,
2005) with results that were in very good spatial agreement with other studies
on intrinsic default-mode activity (Greicius et al., 2003, 2004; Fox et al., 2005).
(ii) Fox and colleagues have in a recent study, where six different seed regions
were used in the analysis of intrinsic activity, shown that the spatial pattern of
the intrinsically active networks during rest is not critically dependent on the
particular default-mode region in which the ROI seed is positioned (Fox et al.,
2005).
2.5. Power density estimations
To gauge changes in the amount of intrinsic, low-frequency BOLD signal
fluctuation for rest compared to the WM task, we used the periodogram method
to compute the average power density estimates for all voxels residing in the
task-negative, default-mode network. The periodogram is a method used to esti-
mate the power spectrum of a signal by finding the discrete Fourier Transform
of the data, and as a final step, computing the squared magnitude of the Fourier
coefficients. Voxels that entered the periodogram analysis were selected on the
basis of an image template constructed from 13 subjects participating in an
earlier study on default-mode activity (Fransson, 2005). The template encom-
passed the precuneus, posterior and anterior parts of the cingulate cortex, medial
prefrontal cortex, lateral parietal cortex, anterolateral temporal cortex and the
parahippocampal gyrus, bilaterally. Before entering the periodogram analysis,
the BOLD signal intensity time courses were band pass filtered (pass band
0.012–0.15 Hz).
2.6. Independent component analysis
Independent component analysis (ICA) was employed as a complementary
method to compare intrinsic, default-mode brain activity during rest and the
working memory task. ICA processing of the EPI data closely followed the
scheme described in detail by Greicius et al. (2004). Briefly, ICA is a mathemat-
ical procedure to decompose, for example, a spatiotemporal signal into inde-
pendent, uncorrelated and non-Gaussian components. The pre-processing steps
involved transforming the smoothed, normalized and realigned EPI volumes into
4D datasets which were subsequently analyzed with the FSL MELODIC soft-
ware (Beckmann & Smith, 2004). In line with Greicius et al. (2004), the number
of output components was set to one-fifth of the total number of EPI scans in
each dataset: in this case 60 independent components for each dataset. Again, in
line with (Greicius et al., 2004), we used a non-linear template-matching proce-
 P. Fransson / Neuropsychologia 44 (2006) 2836–2845
dure to select the best-fit component based on a goodness-of-fit measured with
respect to a default-mode template (Fransson, 2005). A detailed account of the
calculations of the goodness-of-fit measure is given in Greicius et al. (2004).
3. Results
3.1. Behavioural data
Behavioural data was available for 12 of the 14 participating
subjects. The remaining two data sets were lost due to technical
data acquisition problems. For the sustained WM task, the mean
accuracy was 231.7 (S.D. 6.5) out of a possible of 244 and the
mean latency was 1012 ms (S.D. 219 ms). For the epoch version
of the WM task, the mean accuracy was 58.2 (S.D. 3.1) out of
a possible 60 and the mean latency was 820 ms (S.D. 133 ms).
Average subjective measures of task-unrelated thoughts (TUTs)
estimated by ratings on a visual analogue scale (0–100) for rest
were (results for the sustained WM task within parentheses):
attention unrelated to the given task 65 ± 24 (17 ± 17), imagery
63 ± 34 (17 ± 25), inner speech 38 ± 23 (6 ± 7), episodic mem-
ory events 32 ± 28 (1 ± 3) and events that involved thoughts
about the future (planning) 31 ± 28 (5 ± 15).
3.2. Correlational analysis
Intrinsic functional connectivity for rest and the WM task
were investigated using a correlation analysis based on a ROI
positioned in the posterior cingulate cortex (PCC)/precuneus
area. Positive correlations with the PCC/precuneus were found
in the medial prefrontal cortex (MPFC), anterior cingulate cor-
tex (ACC), angular gyrus, inferior and middle temporal cortex,
temporal pole, cerebellum and the parahippocampal gyrus for
both conditions (Fig. 1, left- and middle-hand columns, areas
labelled with a yellow–red colour-scale). Negative correlations
(anticorrelations) were found in the dorso-lateral prefrontal cor-
tex (DLPFC), supplementary motor area (SMA), supramagi-
nal gyrus (SII), dorsal premotor cortex (PM)/frontal eye fields
(FEF), insula, visual areas and the MT area in the temporal
cortex (Fig. 1, left- and middle-hand columns, areas labelled
using a blue–magenta colour-scale). Importantly, all regions that
showed correlational activity in the default-mode network dur-
ing rest, with the exception of the thalamus, cerebellar tonsils,
caudate nucleus and middle temporal gyrus, were also active in
the default-mode network during the sustained version of the
WM task. It should be noted that the spatial extent of the signifi-
cantly correlated clusters in the default-mode network were sub-
stantially reduced for the WM task compared to rest. The overall
reduction of correlational intrinsic activity is also reflected by
the fact that the corresponding t-scores for foci of activation
were much smaller in magnitude for the WM task compared to
the resting state condition. A direct comparison of default-mode
activity revealed relatively stronger intrinsic correlation in the
angular gyrus, MPFC, middle temporal gyrus, temporal pole,
cerebellum and the parahippocampal gyrus bilaterally (two-
sample t-test, p < 0.05, corrected, see Fig. 2 and Table 1). No
voxels in the default-mode network were found to have signifi-
cantly more correlational activity during the WM task compared
2839
to rest. Further, a direct comparison of correlational, intrinsic
activity in the task-positive/dorsal attention network showed a
relatively stronger intrinsic activity during rest in the supram-
aginal gyrus (SII) and insula bilaterally with a tendency for a
spatially more extended activity in the right hemisphere (two-
sample t-test, p < 0.05, corrected, see also Fig. 3 and Table 2). No
voxels in the task-positive network showed significantly more
correlational activity in the WM task compared to rest.
The results from the non-intrinsic, epoch-related paradigm
that contrasts rest with epochs of the WM task are shown
in the right-hand column in Fig. 1. In agreement with previ-
ous neuroimaging studies of verbal working memory, extensive
increases in activity compared to rest were seen in the dorso-
lateral prefrontal cortex, lateral parietal cortex, SMA, insula
and occipital cortex (Cabeza & Nyberg, 2000; Wager & Smith,
2003), whereas decreases in epoch-related activity compared
to rest largely overlapped with the regions implied in the task-
negative, default mode of brain function.
3.3. Power density analysis
Voxels belonging to the task-negative, default-mode network
were selected on the basis of a template constructed from a previ-
ous study of resting-brain default-mode activity (total number of
voxels: 13 725, Fransson, 2005). The amount of low-frequency,
spontaneous BOLD signal fluctuations was estimated by means
of the periodogram method. The mean power density plot of low-
frequency BOLD fluctuations in the default-mode network dur-
ing rest and WM is shown in Fig. 4. A two-sample t-test showed
that the mean power density of intrinsic low-frequency signal
fluctuations in the frequency interval of interest (0.012–0.1 Hz)
was significantly decreased during the WM task compared to rest
(p = 0.035, t = 1.88). In addition, putative regional differences in
power density during rest and the WM task were assessed by
separately comparing mean power density in individual clus-
ters belonging to the default-mode network. We found that
the mean power density of intrinsic fluctuations were signif-
icantly decreased during the WM task in the PCC/precuneus
(8175 voxels, p = 0.009, t = 2.54), left angular gyrus (1662 vox-
els, p = 0.021, t = 2.15) and right angular gyrus (828 voxels,
p = 0.007, t = 2.62) whereas the mean power density did not dif-
fer in the medial prefrontal cortex (3060 voxels, p = 0.36).
3.4. Independent component analysis
Intrinsic activity in the default mode during rest and the WM
task were additionally assessed by decomposing the data into
independent components and performing a match of each indi-
vidual independent component to a default-mode template as
previously described by Greicius and colleagues (Greicius et
al., 2003, 2004). Goodness-of-fit measures for intrinsic activity
with regard to a default-mode template (Fransson, 2005) were
computed for both rest and the WM task using the non-linear
approach outlined in (Greicius et al., 2004). The mean goodness-
of-fit score was found to be significantly lower (p = 0.021, two-
sample t-test) for the WM task (1.82, S.D. 0.41) compared to
rest (2.13, S.D. 0.36), see also Fig. 5.
2840 P. Fransson / Neuropsychologia 44 (2006) 2836–2845

Fig. 1. Intrinsic correlation in the brain with a ROI seed region (10 mm radius sphere centred at [0, −52, 30]) in the PCC/precuneus and all other voxels in the brain
during rest, visual fixation (left-hand column) and during performance of a sustained version of the two-back working memory (WM) task (middle column). Intrinsic
activity in the default-mode task-negative network is shown in a yellow–red colour-scale and the anticorrelated, task-positive network is shown in a blue–magenta
colour-scale. The results from the non-intrinsic, epoch version of the two-back WM task, where periods of the WM task were interleaved with periods of visual
fixation, are shown in the right-hand column. Epoch-related signal increases during the WM task periods are depicted using a red–yellow colour-scale whereas
epoch-related signal decreases during the WM task periods are shown using a blue–magenta colour-scale.
 P. Fransson / Neuropsychologia 44 (2006) 2836–2845 2841

Fig. 2. A direct comparison of intrinsic, correlational activity during rest and sustained performance of the two-back working memory (WM) task in the default-mode
network using a two-sample t-test thresholded at p < 0.05. Relative increases in correlational, intrinsic activity during rest compared to the WM task were observed in
most default-mode regions, including the medial prefrontal cortex, precuneus, posterior cortex cinguli, angular gyrus, parahippocampal gyrus and inferior temporal
cortex. No significant increases in intrinsic activity during the WM task compared to rest were observed in the default-mode network (see also Table 1).

3.5. Correlation between TUT’s and neuroimaging data
In an attempt to investigate whether the degree of experienced
task-unrelated thoughts correlated with neuroimaging data at
the individual level, we performed a correlation analysis using
Spearman’s rank correlation test between the subjective ratings
of task-unrelated thoughts (inner speech, imagery, planning for
the future, episodic memory events and task-unrelated attention)
and the goodness-of-fit scores and mean power density estimates
during rest and the WM task, respectively. However, neither the
mean power density estimate nor the goodness-of-fit score cor-
related significantly with any of the subjective ratings of TUT’s
that occurred during rest and the WM task at the significance
level of p < 0.05.

Table 1
Foci in the default-mode (task-negative) network that showed significantly more correlational activity during rest compared to the WM task
Clustersize Anatomical region X Y Z Brodmann area Peak t-value

L angular gyrus −39 −75 45 10 8.19

4130 L precuneus −3 −63 48 7 7.23
R precuneus 3 −66 30 7 6.70
L middle frontal gyrus −33 18 57 6 7.74
R middle frontal gyrus 33 33 51 6 4.84
2391 L superior frontal gyrus −6 39 39 8 3.67
R superior frontal gyrus 9 45 −12 11 4.53
L superior frontal gyrus −12 45 −12 11 4.63
L middle temporal gyrus −60 −27 −15 20/21 6.58
L middle temporal gyrus −57 −36 −6 21 5.61
513 L parahippocampal gyrus −27 −27 −24 36 4.18
L temporal pole −42 9 −42 21/38 3.47
R middle temporal gyrus 63 −18 −21 20/21 4.60
R temporal pole 48 9 −42 21/38 4.49
470
R middle temporal gyrus 63 −27 −12 20/21 4.36
166 R cerebellum 39 −72 −42 4.75
R cerebellum/tonsils 6 −60 −51 3.70
125 L cerebellum/tonsils −6 −57 −48 3.21
105 R parahippocampal gyrus 30 −18 −24 36 3.17
38 L cerebellum −24 −90 −27 3.39
12 L inferior orbito-frontal gyrus −27 27 −24 11/47 2.74
2842 P. Fransson / Neuropsychologia 44 (2006) 2836–2845

Fig. 3. A direct comparison of intrinsic, correlational activity in the dorsal attention/task-positive network during rest and sustained performance of the two-back
WM task using a two-sample t-test thresholded at p < 0.05. Relative increases in intrinsic activity in the task-positive network during rest compared to the WM task
were found in the supramaginal gyrus and insula bilaterally (see also Table 2). No significant increases in intrinsic activity during the WM task compared to rest
were observed in the task-positive network. Note that the blue–magenta colour-scale is used here to facilitate a comparison of intrinsic activity in the task-positive
network during rest and the WM task shown in Fig. 1.

Table 2
Foci in the task-positive network that showed significantly more correlational activity during rest compared to the WM task
Cluster size Anatomical region X Y Z Brodmann area Peak t-value

R inferior frontal gyrus 57 9 12 6/44 5.80

280
R insula 45 12 6 13/14 5.15
R supramaginal gyrus 66 −21 33 40 6.25
111 R supramaginal gyrus 63 −18 24 40 5.90
R postcentral gyrus 69 −15 18 40/43 4.67
40 L Supramaginal gyrus −66 −27 18 40 4.41
14 L Insula −36 3 9 13/14 4.48

Fig. 4. Estimates of the power spectral density for fMRI signal intensity time
courses in the task-negative, default-mode network during rest and performance
of the two-back working memory task. The graph shows the mean power density
plot averaged across all subjects. A two-sample t-test showed that the mean
power density of intrinsic low-frequency signal fluctuations in the frequency
interval of interest (0.012–0.1 Hz) was significantly decreased during the WM
task compared to rest for the default mode of brain function network (p = 0.035,
t = 1.88).
Fig. 5. Independent component analysis was used to compute individual scores
for goodness-of-fit to a default-mode brain template. The goodness-of-fit for
each subject is shown as a scattergram where the left-hand column contains the
matching scores obtained during rest, whereas scores for the two-back working
memory task are displayed in the right-hand column. A two-sample t-test showed
that the average scores were significantly higher for the rest compared to the WM
task (p = 0.021).
 P. Fransson / Neuropsychologia 44 (2006) 2836–2845
4. Discussion
4.1. Attenuation of the default mode during the WM task
We have presented results from three different approaches
of analysis of intrinsic activity during rest and an attention-
demanding WM task. Results from the ROI-based correlation
analysis, power spectrum estimates of intrinsic fluctuations in
fMRI signal intensity time-courses and the ICA decomposition
are consistent in that they all show that activity in the form of
synchronous, low-frequency BOLD signal fluctuations in the
task-negative, default-mode network persists during the work-
ing memory task, although markedly down-regulated compared
to a resting-state. The subject’s high accuracy in performing the
working memory task combined with the low ratings on the
presence of task-unrelated thoughts is in agreement with the
notion that a successful completion of the WM task requires a
high level of task-directed attention and leaves little space for
self-referential, spontaneous thought. The behavioural measures
recorded for the WM task is concordant with our finding of a
substantially attenuated level of correlational, intrinsic activity
in the default-mode network. Taken together, our results comple-
ments earlier work carried out by McKiernan and co-workers in
that not only task-induced deactivations but also intrinsic, spon-
taneous brain activity in the default-mode regions is modulated
by cognitive load and that the degree of TUTs decreased as a
function of cognitive load (McKiernan et al., 2003, 2006).
It is interesting to regard these results with reference to pre-
vious investigations that have proposed that self-reflection/self-
awareness (D’Argembeau et al., 2005; Johnson et al., 2002;
Kelley et al., 2002) and self-referential judgements of emotion-
ally laden pictures (Gusnard et al., 2001) are chief components
among the cognitive abilities supported by the default-mode net-
work, in particular the ventral parts of the MPFC. In a similar
vein, other constituents of the default-mode network such as
the angular gyrus and the anterolateral temporal cortex have
been ascribed a vital role in representing mental states such as
thoughts, feelings and beliefs, relating not only to oneself but
also to other people (Frith & Frith, 2003). In addition, it has been
suggested that episodic memory retrieval, in particular for events
with an emotional saliency is supported by the precuneus, retro-
splenial cortex, MPFC and the lateral parietal cortex (Cavanna &
Trimble, 2006; Maddock, 1999; Maguire & Mummery, 1999).
All of these default-mode regions were intrinsically active dur-
ing the sustained version of the WM task. Theoretically, it is
quite possible that task-unrelated thoughts occurred during the
approximately 1.5 s in between the user response and the start
of the next trial, in spite of the fact that the subjects had to
actively maintain the memory of the last two words during this
time interval to be able to give a correct answer in the subse-
quent word trial in the WM task. This hypothesis is supported
by the finding that the five subjective measures of TUT’s were
considerably lower compared to rest but, importantly, did not all
equal zero for the WM task. Presumably, if the subjective rat-
ings are good predictors for the amount of experienced TUT’s
at the individual level, one would expect to find a correlation
between the given ratings and the amount of intrinsic activity
2843
in the default-mode network. Although the overall reduction in
reported TUT’s for the WM task is in good agreement with
the overall reduction in intrinsic activity in the default-mode
network, we did not find any statistical evidence for a posi-
tive correlation between the degree of experienced TUT’s and
intrinsic activity at the individual level. The lack of correlation
can in part be explained by the fact that a major part of the
individual ratings given for the WM task were zero, in particu-
lar the ratings for inner speech, episodic memory and planning
for the future, which obviously hamper a correlational analy-
sis. In addition, it should be stressed that the predictive value of
the subjective ratings recorded here might be limited since they
are given retrospectively and ideally represent only an average
score of the amount of experienced TUT’s during the 10 min
scanning periods without any information on which points in
time the TUT’s occurred. Since intrinsic activity were attenu-
ated but not abolished during the WM task, we suggest that the
concept of a default mode, defined as an intrinsically connected
network of brain regions, can be extended to include brain states
present during performance of attention-demanding overt tasks.
The proposed extension of validity for the default mode of brain
function in terms of spontaneous, intrinsic activity expands on
previous results that reported only very moderate influence on
the intrinsic default-mode activity caused by changes in sen-
sory input (Greicius and Menon, 2004) or sensory deprivation
(Burton, Snyder, & Raichle, 2004).
4.2. Reorganization of the task-positive network
The WM task caused an overall suppression of correlational,
intrinsic activity in the task-negative default-mode network with
no additional recruitment of neuronal resources located out-
side the default-mode regions (Fig. 1, middle-hand column,
areas coded using a red–yellow colour-scale). A detailed dis-
cussion of the supposed function of the task-positive/dorsal
attention network during resting-state conditions has previously
been given in Fransson (2005). Here, we note that most of the
active regions in the task-positive/dorsal attention network dur-
ing rest are also intrinsically active during performance of the
WM task (Fig. 1, left-hand and middle columns, areas coded
using a blue–magenta colour-scale). A qualitative visual inspec-
tion of the task-positive, intrinsically driven network during the
sustained WM task (Fig. 1, middle-hand column, areas shown
in a blue–magenta colour-scale) and the increases in activity
observed in the epoch-related WM experiment (Fig. 1, right-
hand column, areas coded using a red–yellow colour-scale) indi-
cate that the DLPFC, SMA, supramaginal gyrus, dorsal PM/FEF,
left insula and visual areas accommodate both epoch-related
signal increases in response to the epoch-related WM task and
correlational intrinsic activity during the sustained WM task,
respectively. However, a quantitative test using a two-sample
t-test failed to show any significant increases in intrinsic activ-
ity in the dorsal attention/task-positive network for the WM task
compared to rest, whereas a significant increase in correlational,
intrinsic activity during rest compared to the WM task were
observed in the supramaginal gyrus (SII) and insula bilaterally
(Fig. 3).
2844 P. Fransson / Neuropsychologia 44 (2006) 2836–2845
4.3. Conscious and unconscious cognitive processing in the
default-mode network?
We have shown that a suppression and reorganization of
intrinsic network activity occurs in response to an attention-
demanding task. Although the subjective ratings of TUT’s given
during the WM task indicate that spontaneous, task-unrelated
mental events were markedly reduced but still occurred in
some subjects, we would like to propose the hypothesis that
the observed suppression of the task-negative, default-mode
network mainly reflects a substantial reduction in conscious,
task-unrelated thoughts during the WM task. We can assume
from the subjective ratings of TUT’s that spontaneous, task-
unrelated mental events have occurred during the WM task, but
we would nevertheless like to propose the hypothesis that there
are two conceptual layers of cognitive processing handled by
the default-mode network. On the one hand, during an absence
of overt task performance our mind is at liberty to initiate,
maintain and end any number of spontaneous, self-referential
mental events, in an arbitrary order. We believe that these events,
such as episodic memory, planning for the future, inner speech
or simulation of behaviour (Ingvar, 1979), reflect thoughts or
the “streams of consciousness” (James, 1890) of which we are
aware, when overt task performance is absent. This proposition
is supported by our finding that the subjective ratings of inner
speech, episodic memory and planning for the future showed
the largest decreases with average ratings close to zero when the
subjects performed the sustained version of the working mem-
ory task. Consequently, this layer of cognitive processing in the
default mode is susceptible to increases and decreases in exter-
nal demand on the attentional and computational resources in the
brain. On the other hand, we speculate that there is a core layer
of intrinsic activity in the default-mode that is not to any greater
extent sensitive to changes in perception, attention or internal
goal-oriented task processing. The exact function of this core
of intrinsic activity is unclear at present, but we speculate that
it represents unconscious and continuously on-going processes
that are necessary to maintain a coherent neuronal representa-
tion of the “self”. We believe that irrespective of how focused
we are on a specific task and no matter how computationally
demanding that task is, we cannot, metaphorically speaking,
“lose track of ourselves”. At all times, the brain needs to have
a coherent mental model of the self. Cognitive faculties that
might be administered by this model include having a sense
of who we are and where in space we are and the passage of
time. Moreover, this model needs to be constantly updated due
to incoming sensory information from the world around us as
well as to incoming internal markers that, for example, signal
pain, hunger or thirst. In this context, we note that metabolic
dysfunction of the default-mode brain regions, in particular the
precuneus and MPFC is common in patients in a vegetative or
minimally conscious state (Laureys, 2005; Laureys, Owen, &
Schiff, 2004).
We have in a previous study suggested that during rest the
two reciprocally and intrinsically active networks might rep-
resent a division of labour in the brain where, in accordance
with previous investigations, the default-mode network is prin-
cipally involved in introspective thought whereas the dorsal
attention/task-positive network during rest is related to extro-
spective attention and readiness for potential changes in the
extra-personal as well as internal environment that are rele-
vant to the individual (Fransson, 2005). In keeping with this
theory, the observed qualitative change in correlational intrinsic
activity from the default mode towards the task-positive network
for the sustained version of the WM task might be tentatively
interpreted as a task-initiated shift from introspectively oriented
attention towards extrospective attention in the sense that the
dorsal attention/task-positive network has to accommodate both
the WM task and extrospective attention. We would like to
emphasize that the suggested division of labour performed by the
intrinsic activity should not be seen as a strict compartmentaliza-
tion of information processing. Rather, to accomplish a coherent
“stream of consciousness” we propose that a binding mechanism
between introspectively and extrospectively oriented attention
exist. We tentatively suggest that the temporal synchronicity of
intrinsic low-frequency fluctuations might reflect such a mech-
anism. Further, it has been suggested that intrinsic activity is
related to the development and maintenance of a probabilistic
model of anticipated events in the brain (Raichle & Gusnard,
2005). We note that the findings and interpretations of intrinsic
activity given here are compatible with such a Bayesian perspec-
tive on the intrinsic activity in the brain (Körding & Wolpert,
2004).
In conclusion, the findings presented in this study comple-
ments previous studies on the effect of cognitive load on task-
induced deactivation in the default-mode network (McKiernan
et al., 2003, 2006) by suggesting that intrinsic activity in the brain
cannot be abolished by task performance, but only modulated.
Consequently, intrinsic brain activity is therefore a property with
wide-ranging validity in neuroimaging research that reflects a
dynamic interplay between widely distributed brain systems that
is modulated rather than interrupted by task performance.
Acknowledgments
The author would like to thank Per Hamid Ghatan, Martin
Ingvar and Mary Rudner for valuable comments on an earlier
version of this manuscript.
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