Neural basis of the emotional Stroop
interference effect in major depression
M. T. Mitterschiffthaler1*, S. C. R. Williams1, N. D. Walsh2, A. J. Cleare1, C. Donaldson1,
J. Scott1,3and C. H. Y. Fu1
1Institute of Psychiatry, King’s College London, UK
2University of Pittsburgh, School of Medicine, Department of Psychiatry, Pittsburgh, PA, USA
3University Department of Psychiatry, Royal Victoria Infirmary, Newcastle upon Tyne, UK
Background. A mood-congruent sensitivity towards negative stimuli has been associated with development and
maintenance of major depressive disorder (MDD). The emotional Stroop task assesses interference effects arising from
the conflict of emotional expressions consistent with disorder-specific self-schemata and cognitive colour-naming in-
structions. Functional neuroimaging studies of the emotional Stroop effect advocate a critical involvement of the an-
terior cingulate cortex (ACC) during these processes.
Method. Subjects were 17 medication-free individuals with unipolar MDD in an acute depressive episode (mean age 39
years), and 17 age-, gender- and IQ-matched healthy volunteers. In an emotional Stroop task, sad and neutral words
were presented in various colours, and subjects were required to name the colour of words whilst undergoing func-
tional magnetic resonance imaging (fMRI). Overt verbal responses were acquired with a clustered fMRI acquisition
Results. Individuals with depression showed greater increases in response time from neutral to sad words relative to
controls. fMRI data showed a significant engagement of left rostral ACC (BA 32) and right precuneus during sad words
in patients relative to controls. Additionally, rostral ACC activation was positively correlated with latencies of negative
words in MDD patients. Healthy controls did not have any regions of increased activation compared to MDD patients.
Conclusions. These findings provide evidence for a behavioural and neural emotional Stroop effect in MDD and
highlight the importance of the ACC during monitoring of conflicting cognitive processes and mood-congruent pro-
cessing in depression.
Received 26 March 2006; Revised 5 July 2007; Accepted 11 July 2007; First published online 10 September 2007
Key words: Anterior cingulate cortex, depression, emotional Stroop.
Increased levels of negative mood has been related to a
processing and recall bias for negative information
(Teasdale & Fogarty, 1979; Teasdale & Russell, 1983).
This processing bias has been shown in experimen-
tally induced transient sadness in healthy individuals
as well as in clinical depression. This mood-congruent
heightened sensitivity towards negative stimuli and
prolonged processing of emotionally negative infor-
mation has been proposed to play an important role
in the development and maintenance of unipolar
depression. Cognitive theories of mood-biased pro-
cessing, such as schema theory (Beck et al. 1979) and
network theory of affect (Bower, 1981) postulate that
during a depressive state memory resources are
bound to negative stimuli, which leads to an attenu-
ation in memory capacity for incoming information
of a positive emotional value (Ellis & Ashbrook, 1988).
Some corroborative evidence for these theories
comes from behavioural studies investigating proces-
sing of negative stimuli (Gotlib & McCann, 1984;
Williams & Broadbent, 1986; Gotlib & Cane, 1987) and
mood-congruent memory biases in depression (Lloyd
& Lishman, 1975; Clark & Teasdale, 1982; Bradley et al.
The emotional Stroop task is a potentially useful
tool to assess mood-congruent processing, by measur-
ing the attentional bias towards negative stimuli.
In this task affective words are presented in various
colours, and subjects are required to name the
colour of words rather than perform the automatic
and overlearned response of reading the word
drawn to disorder-specific emotional expressions
trigger memories of personal loss and failure. These
* Address for correspondence: M. T. Mitterschiffthaler, Ph.D.,
Neuroimaging Research Group, Clinical Neuroscience, PO Box 89;
Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
Psychological Medicine (2008), 38, 247–256.
f 2007 Cambridge University Press
Printed in the United Kingdom
disorder-specific self-schemas are then in conflict
with a cognitive colour-naming instruction (MacLeod,
1991; Segal et al. 1995). Increased latencies are the
result of this process.
A number of behavioural studies of emotional
Stroop paradigms have observed these interference
effects in depression (Williams & Broadbent, 1986;
Gotlib & Cane, 1987; Segal et al. 1995; Kerr et al. 2005).
Negative, positive and neutral words have been used
to investigate, whether these interferences are elicited
simply through the affect component rather than
the negative information per se. Although a few studies
report interference to affective material in general
(Taylor & John, 2004), the majority of reports support
the notion that depressed individuals display a mem-
ory bias for negative material centred around loss and
failure (Watkins et al. 1996; Neshat-Doost et al. 1998;
Dudley et al. 2002; Koster et al. 2005).
Neuroimaging studies suggest that the anterior
cingulate cortex (ACC) plays a major role in Stroop
task performance (Pardo et al. 1990; Bench et al. 1993;
Taylor et al. 1994, 1997; George et al. 1994; Carter et al.
1995; Bush et al. 1998; Peterson et al. 1999; Banich et al.
2000; Mead et al. 2002; Gruber et al. 2002; Langenecker
et al. 2004; Kerns et al. 2004). The ACC is at the core
of organizing endogenous, individual-driven control
processes and exogenous control processes, that are
influenced by environmental distractions (Posner,
1980). It is implicated in error monitoring and atten-
tional processes (Paus, 2001), coordinating cognitive
control and conflict processes experienced during in-
compatible conditions (Carter et al. 2000), and it is
further involved in the elicitation of autonomic re-
sponses during cognitive challenges (Critchley et al.
In healthy individuals, during performance of an
emotional Stroop task Whalen and colleagues (1998)
observed greater neural activity in the ACC with
negative words and in absence of a behavioural inter-
ference effect. In individuals with a mood disorder,
George and colleagues (1997) found greater latencies
during a sad word condition relative to healthy con-
trols but did not observe any significant differences in
their neural activity. However, the patient group had a
number of diagnoses and their affective state varied
from euthymic to moderate depression. In individuals
with bipolar disorder during a euthymic state, Malhi
and colleagues (2005) reported an emotional Stroop
effect and increased ACC engagement, although all
patients were taking medication.
A further, related, method of assessing a mood-
influenced bias is through emotional go/no-go tasks.
Sets of target and distractor words are presented and
participants are instructed to respond to target words
immediately by pressing a corresponding button. In
these paradigms low latencies are a direct measure
of a mood-congruent bias (Murphy et al. 1999). These
tasks have been used in behavioural as well as func-
tional magnetic resonance imaging (fMRI) research
(Murphy et al. 1999; Elliott et al. 2002; Erickson et al.
2005). Increased activation during sad target words
has been found for major depressive disorder (MDD)
patients, relative to positive words and to controls, in
the rostral ACC and medial prefrontal cortices (Elliott
et al. 2002), further supporting the role of the ACC in
selective attention and mood-congruent processing.
In a fMRI study utilizing an original Stroop task,
increased activation was found in the rostral ACC and
the dorsolateral prefrontal cortex in unmedicated
MDD patients, compared to controls (Wagner et al.
2006). Dorsal ACC activation did not differ between
Due to a high variability in sample characteristics
and paradigm specifications findings of previous re-
search are not always easy to interpret and compare.
The present study aimed to control some factors, such
as treatment effects and co-morbidity to investigate the
relationship between attentional biases and mood-
congruent processing in a group of medication-free
patients with unipolar MDD. All MDD subjects were
experiencing an acute depressive episode of moderate
severity. We hypothesized that MDD patients would
show an attentional bias in response to negative words
which would be expressed in increased latencies dur-
ing colour-naming emotional words. On a neural
level, we expected an engagement of the ACC during
processing of negative emotional words. As we did
not use positive emotional stimuli our study cannot
answer the question of effects of emotional arousal
per se; however, as outlined above, emotional Stroop
effects in depression have been shown to be mostly
specific to negative stimuli.
Method and materials
After full explanation of the study procedures, all
participants provided written, informed consent. The
study was approved by the South London and
Maudsley NHS Trust Research Ethics Committee.
Seventeen right-handed individuals (mean age 39.3
years, S.D.=9.4) meeting DSM-IV criteria for a diag-
nosis of unipolar major depression, acute depressive
episode, were recruited through local newspaper ad-
vertisement. The diagnosis was obtained through the
SCID-I, patient version (First et al. 1997) and a clinical
interview with a board-certified psychiatrist. Inclusion
criteria included a score of o18 on the 17-item
Hamilton Depression Rating Scale (HAMD; Hamilton,
248 M. T. Mitterschiffthaler et al.
1960). All participants were free of psychotropic
medication for a minimum of 4 weeks at the time of
inclusion into the study or a minimum of 8 weeks if the
previous medication had been fluoxetine. Apart from
psychotropic medication, one patient took trimetho-
prim, one received treatment for high cholesterol, one
had an oestrogen patch, one patient had a nicotine
patch and one patient sporadically used a nasal spray
for hay fever. Exclusion criteria were co-morbidity
with other Axis I disorders, current or past neuro-
logical disorders, history of neurological trauma re-
sulting in loss of consciousness, reported substance
or alcohol abuse within 2 months prior to study par-
ticipation, and criteria that are contra-indicative
for having a MRI scan. Seventeen right-handed vol-
unteers, matched by age, gender and IQ (mean age
39.4 years, S.D.=9.2), without a personal or family
history of psychiatric disorders, head injury resulting
in unconsciousness, neurological disorder and current
substance abuse were recruited through local adver-
tisements. The ratio of smokers per group was 3:2,
with three smokers in the patient group.
All participants completed the Beck Depression
Inventory (BDI; Beck et al. 1961), and were assessed
with the HAMD (Hamilton, 1960) and the Wechsler
Abbreviated Scale of Intelligence (WASI; Wechsler,
1999) (Table 1).
Selection and assessment of words
A pilot study was first carried out to confirm the ap-
propriateness of 40 negative and 40 neutral words and
to assess their suitability in a clinical population.
Fifteen healthy individuals (mean age 27.9 years,
S.D.=7.8) and 15 medication-free individuals with
mild depression (mean age 32.6, S.D.=10.9; mean BDI
score 15.4, S.D.=2.9) participated in the pilot study.
Eighty words were chosen from two lists of emotional
and non-emotional words (John, 1988; Bradley &
Lang, 1999) and divided into two groups based on
sad or neutral valence. Stimulus groups were matched
for standardized lexical word frequency (Francis &
Kucera, 1982), pronounceability (expressed in number
of syllables) and word length. The John (1988) list
contained word associations, and words were chosen
that produced the lowest number of negative and
happy associations for neutral words and the lowest
number of happy associations for sad words. The
Bradley & Lang (1999) affective word norms were
used to determine emotional valence and word fre-
quency. Mean sad word frequency was 28.20 (S.D.=
35.21) and mean word length was 6.75 (S.D.=1.81).
Mean neutral word frequency was 33.95 (S.D.=47.03)
and mean word length was 6.83 (S.D.=1.82). Inde-
pendent-sample t tests confirmed that words did not
differ significantly on frequency, pronounceability, or
word lengths (all p>0.54), but did differ in emotional
Forty negative and 40 neutral words (see Appendix)
were presented on a laptop computer. Words were
collated into blocks of eight words per emotional
category, repeated five times whereby each word
was presented only once with a presentation time
of 700 ms per word. All words appeared on black
background in red, blue, green or yellow colour,
pseudo-randomized across the two valence categories.
Participants were informed that they would see
words appearing individually on the screen, coloured
in red, green, yellow or blue. They were instructed to
name the colour of the word as quickly as possible,
rather than reading the word. Reaction time record-
ings were done through onset of speech.
Reaction times were evaluated using a valencer
group (2r2) repeated-measures ANOVA. The analy-
sis revealed main effects of valence [F(1,28)=21.98,
p<0.001] and group [F(1,28)=5.60, p=0.03] and a
valencergroup interaction effect [F(1,28)=8.07, p=
0.01]. This preliminary study confirmed an emotional
interference effect for sad emotional stimuli in the
patient group through prolonged latencies in colour
naming of emotionally charged words.
The emotional Stroop task was projected onto a mirror
inside the scanner. Head movement was restricted
with foam padding and a Velcro strap across partici-
pant’s forehead. Participants were required to name
the colour of the presented word. Stimuli were then
presented in a blocked design of ten alternating blocks
of eight sad and eight neutral words, as described
above. Volunteers’ vocal responses were recorded by
using a MRI compatible microphone and software
that monitors the input to the computer soundcard. As
Table 1. Demographics and mean scores of depression measures
Mean age (years)
Full Scale IQ
14 F/3 M
14 F/3 M
MDD, Major depressive disorder; HAMD, Hamilton
Depression Rating Scale; BDI, Beck Depression Inventory.
Emotional Stroop interference in major depression249
soon as a vocal response was detected reaction times
were measured. For each subject microphone settings
were adjusted in order to account for individual dif-
ferences in loudness of speaking voice. Each word was
presented for 700 ms within a 2000 ms quiet period
which allowed recording of their vocal responses in
the relative absence of scanner noise. After 2000 ms
(700 ms word presentation+1300 ms blank screen)
image collection was carried out. The clustered/sparse
image acquisition process has been used previously
and has been found suitable for recording of vocal re-
sponses and minimizing the effects of head movement
artefacts associated with verbal responses in healthy
and patient groups (Fu et al. 2006). An auditory (.wav)
file was recorded for each individual to ensure accu-
racy of response. Additionally, volunteers’ responses
were monitored by a researcher (M.T.M. or N.D.W.)
through headphones and by pressing a corresponding
coloured button on a button box.
A 1.5 T General Electric Signa MR Imaging sys-
tem (General Electric Medical Systems, Milwaukee,
WI, USA)was used toacquire84T2-weighted echopla-
nar images depicting blood-oxygen-level dependent
(BOLD) contrast. For each acquired volume 22 near-
axial slices parallel to the intercommissural plane were
collected over 2000 ms allowing for a silent period of
2000 ms (repetition time 4000 ms, echo time 40 ms, flip
angle 90x, slice thickness 5 mm, interslice gap 0.5 mm,
matrix size 64r64).
MANOVA was carried out using group (MDD, con-
between MDD patients and controls on psychometric
measures (dependent variables: HAMD, BDI, WASI).
To test differences in reaction time and stimulus
category between patients and controls, repeated-
measures ANOVA was carried out using valence (sad,
neutral) as within-group variable, group (MDD, con-
trols) as between-group variable and reaction time (in
ms) as dependent variable. Post-hoc t tests were carried
out to follow-up significant main and interaction ef-
fects, two independent-sample t tests (sad and neutral)
and two paired-sample t tests (MDD and controls).
The a-level was set at 0.025 for each pair of tests.
Images were pre-processed and analysed using the
Statistical Parametric Mapping (SPM2, Wellcome De-
partment of Cognitive Neurology, London) software
package on a Matlab platform. The 84 images func-
into a standard stereotaxic space using a Montreal
Neurological Institute EPI template and the coordinate
system of Talairach & Tournoux (1988) and smoothed
using an 8 mm Gaussian kernel filter full-width-
at-half-maximum to permit application of Gaussian
random-field theory and to facilitate inter-subject
averaging. The first four images were then discarded.
Group analysis was performed using a random-
effects model that incorporated a two-stage hier-
archical procedure. The first level analysis allowed
computation of individual mean images that corre-
sponded to the main contrasts of interest. The time
series was modelled as a block-design with the tem-
poral delay in BOLD response corrected for by a
canonical haemodynamic response function. Contrasts
were performed of the main effect of each affective
state: negative>neutral and neutral>negative.
The significance of individual observations was
tested in two second-level analyses by combining
contrast images using one-sample t tests [p<0.05,
family-wise error (FWE)] to assess groups individu-
ally and a two-sample t test. A two-sample t test
examined differences between groups on key con-
trasts. A threshold of p<0.05, FWE was used to dis-
cuss brain areas without an a priori hypothesis. To
discuss activation in the ACC, an uncorrected thresh-
old of p<0.001 and small-volume correction (SVC)
were applied. A general linear model was used to
determine voxel-wise t statistics. This model estimates
the error variance for each condition of interest across
subjects, rather than across scans and therefore pro-
vides a stronger generalization to the population from
which data are acquired. The t statistics were normal-
ized to Z scores and significant clusters of activation
were determined. To confirm validity of results ac-
quired through an uncorrected p<0.001, region of in-
terest (ROI) analysis using the Marsbar toolbox
implemented in SPM2 was performed to identify
significant activation levels in the ACC. Extracted
data were analysed with SPSS software (SPSS Inc.,
Chicago, IL, USA) using an independent-sample t test.
Furthermore, ROI data was used to investigate re-
(BDI, HAMD). Pearson correlations were calculated
on activation levels, mean latencies as well as clinical
Analysis of clinical measures revealed significant
differences between the two groups in HAMD
250M. T. Mitterschiffthaler et al.
[F(1,27)=1550.47, p<0.001] and BDI [F(1,27)=128.69,
An ANOVA of reaction times of 30 datasets (four
datasets could not be analysed due to problems with
response recordings during neuroimaging) revealed
significant main effects of valence [F(1,28)=25.01,
pf0.001], indicating that both groups showed an in-
creased reaction time with sad words relative to neu-
tral words, a main effect of group [F(1,28)=0.02],
indicating that depressed patients displayed increased
latencies in response compared to controls, and an in-
teraction effect of valencergroup [F(1,28)=10.27,
p=0.03], suggesting a greater difference in latency
between neutral and negative stimuli in patients than
in controls (Fig. 1). Post-hoc analyses to explain the in-
teraction effect revealed that the two groups differed
significantly on negative (t=3.89, df=28, p=0.004)
but not neutral (t=1.81, df=28, p=0.08) stimuli. Post-
hoc analyses also revealed significant effects of valence
in both the MDD (t=4.59, df=14, p<0.001) and the
control (t=2.90, df=14, p=0.01) groups.
For the purpose of completeness results are re-
ported from the individual group analysis and be-
tween-group analysis. Results from between-group
comparisons are discussed.
Effect of affect: negative words>neutral words
Controls. There was a significant bilateral increase in
activation in the middle frontal/superior frontal gyrus
(BA 10, BA 46: x=x30, y=62, z=14; p=0.003,
MDD patients. In this group sad words were associ-
ated with a significant increase in activation in the left
ACC (BA 32: x=x10, y=32, z=28; p=0.001,
Z=4.05), right precuneus (BA 7: x=6, y=x60, z=42;
p=0.01, Z=4.55), left middle temporal gyrus (BA 39:
x=x52, y=x72, z=24; p=0.02, Z=3.89), left thala-
mus (x=x26, y=32, z=4; p=0.05, Z=3.68), right
cerebellum (x=8, y=x46, z=x6; p=0.02, Z=3.60)
and left middle frontal gyrus (BA 6: x=x26, y=10,
z=58; p=0.01, Z=3.55).
Main effect of group: negative words>neutral words
MDD patients relative to controls activated the left
ACC (BA 32: x=x5, y=30, z=24; p<0.000, Z=3.68;
after SVC: p=0.004, Z=3.68) and right precuneus
(BA 7: x=2, y=x60, z=44; p=0.02; FWE: Z=4.75)
more strongly. Controls, relative to MDD patients,
displayed no significant increase in activation in re-
sponse to sad word stimuli (Fig. 2).
Results from ROI analysis confirmed a significant
difference between patients and controls on ACC ac-
tivation (t=3.97, df=32, pf0.001).
Correlations with clinical measures and latencies
There was a significant correlation between mean
signal change in the rostral ACC and latencies in
response to negative emotional words (r=0.68,
p=0.003) in MDD patients only (Fig. 2). We did not
find significant correlations between negative word
latencies and rostral ACC activation in healthy con-
trols. Furthermore, correlations with clinical measures
(HAMD, BDI) and brain activation in the rostral ACC
did not produce significant results (r=1.39, p=0.98).
This could be due to the small range of HAMD and
BDI scores, since all patients were acutely depressed.
The present study investigated an emotional Stroop
interference effect at a behavioural and a neural level
in medication-free individuals with unipolar de-
pression, during an acute depressive episode of mod-
erate severity. We observed greater response latencies
with negative compared to neutral words in MDD
patients compared to healthy controls, which was as-
sociated with greater activity in the rostral ACC and
Increased latencies in patients probably reflect an
interference effect in response to self-referent schemas
(Beck et al. 1979) and networks (Bower, 1981). The
negative self-referent schema in depressed patients
provides a facilitating basis for incoming negative in-
formation resulting in prolonged and sustained pro-
cessing of mood-congruent information reflected in
longer reaction times. Although there was also an
overall increase in reaction time across both word
Fig. 1. Mean latencies and standard deviations for major
depressive disorder (MDD) patients and controls during
colour-naming negative (
) and neutral ( ) words during
the fMRI experiment.
Emotional Stroop interference in major depression 251
types in MDD patients compared to controls, psycho-
motor slowing and information processing is typical
of depression (Caligiuri & Ellwanger, 2000; Tsourtos
et al. 2002; Rogers et al. 2004). However, the groupr
valence interaction effect indicates an even greater
emotional Stroop effect in depressed patients relative
to healthy controls.
The fMRI data revealed greater engagement in the
rostral ACC with negative words relative to neutral
words in depressed individuals. The overactive rostral
ACC in response to negative words suggests a contri-
bution to the attentional bias towards mood-congruent
information. This interpretation is further supported
by the finding of a positive correlation between ACC
activation and latencies of negative words. This find-
ing suggests that the rostral ACC is associated with the
interference process. MDD patients may be less able to
disregard the emotional content of the presented
words resulting in increased reaction times. The ros-
tral ACC is a critical component in the pathology of
depression with a role in assessing emotional salience
which is thought to be dysfunctional in depression
Elliott and colleagues (2002) similarly found greater
ACC activation with sad words in depressed patients
and during happy words in controls. In a counting
Stroop paradigm, Whalen and colleagues (1998) found
that the emotional condition led to signal increase in
the rostral ACC in healthy controls. Moreover, a hy-
perfunction of the rostral ACC has recently been ob-
served in a fMRI study of an original Stroop task
(Wagner et al. 2006). During an incongruent colour-
naming condition MDD patients displayed signal in-
crease in the rostral ACC compared to healthy controls
(Wagner et al. 2006).
The rostral ACC is involved in attention allocation
and conflict monitoring. The emotional Stroop task
presents a cognitively demanding challenge to par-
ticipants, as it requires suppression of a highly trained
and therefore very early (in terms of information pro-
cessing) response, i.e. naming the word, in favour of a
more complex process, i.e. naming the colour.
Resolving this conflict relies heavily on response
selection and executive control. In these circumstances
an initial response has to be overridden by a correct
response. This overriding process could be reflected in
an engagement of the rostral ACC (Botvinick et al.
1999) as mood-congruent trials that withdrew atten-
tion from the task instructions led to signal increase
in this region. Neutral word conditions did not
conflict with the highly overlearned and automated
colour- naming procedure in depression.
A recent study in healthy volunteers employing a
modified version of an emotional Stroop task also
found both rostral ACC and amygdala activation as-
sociated with emotional conflict (Etkin et al. 2006).
Rostral ACC signals increased when conflict resol-
utions were found while amygdala activation was
seen during emotionally conflicting conditions. Etkin
and colleagues (2006) conclude that the rostral ACC
could be a key regulator of amygdalar activity.
Amygdala activation is seen during emotional Stroop
tasks in other patient groups in relation to disorder-
specific words (van den Heuvel et al. 2005). In the
present study, we did not observe greater amygdala
activity in depressed patients relative to healthy con-
trols, which may have reflected a top-down suppress-
ive processing from the ACC to the amygdala. This
may be examined further in an effective connectivity
0 0.20.40.6 0.8 1.01.21.4
Neural response at x = –5, y = 30, z = 24
Mean reaction times
Fig. 2. Sagittal view of significantly increased activation in the left anterior cingulate cortex (ACC) (x=x5, y=30, z=24) in a
between-group comparison, superimposed on a single-subject template. The graph on the right shows the correlation between
activation in the ACC and latencies for colour-naming negative words in major depressive disorder patients (r=0.68, p=0.003).
252 M. T. Mitterschiffthaler et al.
An additional region that was significantly acti-
vated in MDD patients during the affective condition
was the precuneus. The precuneus holds widespread
connections with the prefrontal cortex (Goldman-
Rakic, 1988) and shows a direct connectivity relation-
ship with the dorsal ACC. Its involvement has been
reported in a range of cognitive processes such as re-
sponse selection (Banich et al. 2001), working memory
(LaBar et al. 1999), problem solving and reasoning
(Elliott & Dolan, 1998) and verbal processing (Pinel
et al. 2001; Fu et al. 2006). Engagement of both the
rostral ACC and the precuneus probably reflect in-
creased exogenous attention in the ACC to negative
words and simultaneously heightened endogenous
attention (Posner, 1980) to memory retrieval (Nyberg
et al. 2000), visual imagery (Krause et al. 1999) and
phonological processes (Cabeza & Nyberg, 2000).
A number of limitations of this study have to be
discussed. First, all emotional word stimuli had a
effects in patients could have been due to the
emotional content rather than the negative valence of
the words, although the findings are consistent with
neuropsychological theories of Beck (Beck et al. 1979)
and Bower (1981). Previous research has also shown
that emotional interference in depression is mainly
linked to negative word processing. Second, both
patients and controls displayed increased latencies in
response to negative words (although only very weak
in controls), the finding could simply reflect induced
conflict rather than a pathological feature of de-
pression. This finding could further imply that nega-
tive words had a greater neuronal demand, rather
then reflecting greater interference in depressed
patients. Future studies should address this caveat
amounts of cognitive interference as well as words
across different emotional categories, to investigate
whether neural demands are generally higher during
emotional words. This issue touches upon a general
problem in fMRI research, namely that of the re-
lationship between brain functional and behavioural
measures. In the present study it is difficult to disen-
tangle whether the increased processing of sad stimuli
in depressed patients caused enhanced brain acti-
vation or vice versa. A final potential limitation of
the current study could be the application of an un-
corrected significance level. However, as our analysis
was hypothesis driven and the findings were con-
firmed in a ROI analysis this approach is accepted and
in accordance with previous MRI literature (Elliott
et al. 2002; Wagner et al. 2006).
To summarize, depression is associated with an
emotional interference effect in response to emotion-
ally salient word stimuli on a behavioural and neural
level. The behavioural interference effect was reflected
in significantly prolonged latencies in response to
negative adjectives and verbs in patients with MDD
relative to healthy controls. On a neural level, in-
creased engagement of the rostral ACC and precuneus
in MDD patients was observed during processing of
sad word stimuli. These findings underline the role of
the rostral ACC in the determination of the degree
of emotional conflict or mood-biased cognitions, par-
ticularly in depression. However, further research
should be conducted addressing more specifically be-
havioural and neural interference effects in response
to words of different emotional categories.
Appendix. Negative and neutral word stimuli
Sad words Neutral words
This study was supported by a NARSAD Young
Investigator Award to Cynthia Fu. The authors thank
the volunteers and the staff of the MRI Unit, Maudsley
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