Content uploaded by Christophe Recasens
Author content
All content in this area was uploaded by Christophe Recasens on Mar 28, 2014
Content may be subject to copyright.
Conscious and subliminal conflicts in normal subjects
and patients with schizophrenia: The role of the
anterior cingulate
Stanislas Dehaene*
†
, Eric Artiges
‡
, Lionel Naccache*, Catherine Martelli
‡
, Armelle Viard
‡
, Franck Schu
¨
rhoff
§
,
Christophe Recasens
§
, Marie Laure Paille` re Martinot
‡§
, Marion Leboyer
§
, and Jean-Luc Martinot
‡
*Institut National de la Sante´ et de la Recherche Me´ dicale–Commissariat a` l’Energie Atomique Unit 562 ‘‘Cognitive Neuroimaging,’’ and
‡
Institut National
de la Sante´ et de la Recherche Me´ dicale–Commissariat a` l’Energie Atomique Research Team 02-05 ‘‘Brain Imaging in Psychiatry,’’ Institut Fe´de´ratif de
Recherche 49, Service Hospitalier Fre´de´ ric Joliot, Commissariat a` l’Energie Atomique兾Direction des Sciences du Vivant, 91401 Orsay Cedex, France; and
§
Psychiatry Department, Hoˆ pital Albert Chenevier, Assistance Publique-Hoˆ pitaux de Paris, 94010 Cre´ teil Cedex, France
Edited by Marcus E. Raichle, Washington University School of Medicine, St. Louis, MO, and approved September 11, 2003 (received for review
August 14, 2003)
The human anterior cingulate cortex (ACC), which is active during
conflict-monitoring tasks, is thought to participate with prefrontal
cortices in a distributed network for conscious self-regulation. This
hypothesis predicts that conflict-related ACC activation should
occur only when the conflicting stimuli are consciously perceived.
To dissociate conflict from consciousness, we measured the be-
havioral and brain imaging correlates of a motor conflict induced
by task-irrelevant subliminal or conscious primes. The same task
was studied in normal subjects and in patients with schizophrenia
in whom the ACC and prefrontal cortex are thought to be dys-
functional. Conscious, but not subliminal, conflict affected anterior
cingulate activity in normal subjects. Furthermore, patients with
schizophrenia, who exhibited a hypoactivation of the ACC and
other frontal, temporal, hippocampal, and striatal sites, showed
impaired conscious priming but normal subliminal priming. Those
findings suggest that subliminal conflicts are resolved without ACC
contribution and that the ACC participates in a distributed con-
scious control network that is altered in schizophrenia.
neuroimaging 兩 priming 兩 consciousness 兩 psychiatry
T
he anterior cingulate cortex (ACC) is active during a variety
of cognitive tasks that involve mental effort (1, 2). Whether
a single overarching theory of ACC function can account for this
diversity of findings remains a matter of some debate. However,
the involvement of the ACC in many tasks can be explained by
its role in the detection of conflicting response tendencies (3–7).
The conflict-monitoring model has been implemented as a
working simulation that accounts for some of the major condi-
tions known to activate the ACC, including flanker interference
(3), color-word Stroop interference (5), and error detection (8,
9). Furthermore, it has led to new observations of a dissociation
between ACC and prefrontal cortex (PFC) activity: when cog-
nitive control diminishes, PFC decreases, but ACC activity
increases together with error rate, presumably due to an increase
in conflict (5).
In the present work, we examine whether the ACC is involved
in any form of conflict monitoring, or more specifically with
conscious monitoring. Posner (10, 11) proposed a broad role for
ACC in the conscious self-regulation of behavior, based on its
activation during conscious effortful tasks and its reciprocal
anatomical connectivity with many distant prefrontal and limbic
regions. Dehaene et al. (12–14) further suggested that ACC is an
important node in a distributed ‘‘conscious neuronal workspace’’
comprising neurons with long-distance connections that distrib-
ute information broadly to many higher cortical and subcortical
targets, thus providing a possible neural basis for conscious
access and flexible adaptive behavior. Within this distributed
network, the ACC may play a particular role in the computation
and dissemination of information about anticipated emotions
and rewards, which is essential for conscious self-regulation and
decision making (12, 15, 16). This view fits with the finding of
ACC activation on conscious conflict or error trials. In addition,
it can account for several neuroimaging studies that have evi-
denced increased joint cingulate and prefrontal activity during
conscious perception relative to a comparable nonconscious
stimulation, often in the absence of obvious response conflicts
(17–20).
To examine the relation between ACC and consciousness, we
induced motor conflict in the absence of consciousness by relying
on a previously studied subliminal priming paradigm (refs. 21–23
and Fig. 1). In this task, subjects are asked to decide whether
target numbers are larger or smaller than 5. Unbeknownst to
them, the prior subliminal presentation of another masked
number for 43 ms affects their performance. Response times are
faster when the hidden prime and the visible target are congru-
ent (both larger or both smaller than 5) than when they are
incongruent (one larger and the other smaller). By using func-
tional MRI (fMRI) and event-related potentials, the source of
this congruity effect was traced to a subliminal lateralized motor
preparation induced by the prime, which conflicted with the
preparation of the response to the target (21).
In the present work, we adapted this paradigm to measure
behavioral and fMRI responses to conscious and subliminal
sources of conflict. On different blocks, the prime could be
masked and therefore essentially invisible, or it could be un-
masked by removing the random letter masks, thus requiring
subjects to actively inhibit prime processing (Fig. 1). Based on
earlier work, we expected both conditions to lead to measurable
conflict effects in response times. However, if ACC activation
requires a conscious appraisal of the conflicting stimuli, then
only the conscious conflict situation should lead to increased
ACC activity, together with extended activity in a distributed
cortical network including PFC.
To further probe the relation between conflict, consciousness,
and a distributed network including ACC and PFC, we compared
the behavioral and fMRI responses in normal controls and in
patients with schizophrenia. Converging investigations have
revealed that patients with schizophrenia exhibit distributed
impairments in ACC, PFC, and other interconnected regions,
such as the hippocampus and cerebellum. Anatomically, neuro-
nal density is reduced in ACC and PFC (24), and the amount of
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: ACC, anterior cingulate cortex; PFC, prefrontal cortex; RT, response time;
fMRI, functional MRI.
†
To whom correspondence should be addressed at: Institut National de la Sante´ etdela
Recherche Me´dicale-Commissariat a` l’Energie Atomique, Service Hospitalier Fre´de´ric Jo-
liot, 4 Place du Ge´ne´ral Leclerc, 91401 Orsay Cedex, France. E-mail: dehaene@shfj.cea.fr.
© 2003 by The National Academy of Sciences of the USA
13722–13727
兩
PNAS
兩
November 11, 2003
兩
vol. 100
兩
no. 23 www.pnas.org兾cgi兾doi兾10.1073兾pnas.2235214100
reduction in ACC gray matter and underlying white matter
correlates with the severity of negative symptoms and executive
dysfunction (25–28). Functionally, patients with schizophrenia
exhibit reduced ACC and PFC metabolism at rest (29), and
altered ACC and PFC activation in conflict tasks (30–32).
The functional connectivity between ACC and PFC is also
reduced (33).
We reasoned that schizophrenia provides a testing ground for
theories of the engagement of ACC and PFC in a distributed
network for conscious regulation. Such theories predict that
patients with schizophrenia would exhibit a normal subliminal
conflict effect and would be impaired only in the conscious
monitoring of conflict. This predicted dissociation of subliminal
and conscious processing in schizophrenia has not been studied
directly in the literature (but see refs. 34–38). Given the evidence
for multiple, distributed sites of brain dysfunction in schizophre-
nia, including ACC and PFC, the finding of preserved subliminal
priming would provide strong evidence that ACC and PFC are
not involved in automatic conflict resolution, but solely in
conscious monitoring.
Methods
Participants. Eighteen neurologically normal subjects (mean age
27.4 yr, range 18–44 yr) and 15 patients with schizophrenia
(mean age 28.1 yr, range 19–36 yr), matched in age and in years
of education, were tested. All were right-handed males and
native speakers of French. Exclusion criteria included alcohol or
other drug abuse, depression, neurological disease, or impaired
visual acuity. Patients met Diagnostic and Statistical Manual of
Mental Disorders–IV criteria for schizophrenia and were re-
cruited from psychiatric departments of the Assistance Publique,
Hoˆpitaux de Paris. They had a chronic course and were stabilized
with a moderate dose maintenance neuroleptic treatment. None
were receiving antidepressants, lithium, or electro-convulsive
therapy at the time of testing. Patients scored 49 ⫾ 18 on the
Scale for the Assessment of Negative Symptoms (SANS), and
20 ⫾ 17 on the Scale for the Assessment of Positive Symptoms
(SAPS). On the Positive and Negative Syndrome Scale
(PANSS), their scores were 23 ⫾ 7 for negative symptoms, 14 ⫾
6 for positive symptoms, and 35 ⫾ 9 for general psychopathology.
Behavioral data were available for all subjects, but, due to
motion artifacts and other technical difficulties, fMRI data were
analyzed only in 12 controls and 13 patients. All experiments
were approved by the French Regional Ethical Committee for
Biomedical Research (Hoˆpital de Biceˆtre), and subjects gave
written informed consent.
Stimuli. The stimulus set consisted of 64 pairs of prime and target
numbers, each consisting of the numbers 1, 4, 6, and 9 written in
either Arabic or verbal (spelled-out) format. Subjects were asked
to compare each target number with 5, pressing the right-hand
key as fast as possible for numbers larger than 5 and the left hand
key for numbers smaller than 5. The following factors were
manipulated: target notation (Arabic or verbal), target distance
(close or far from 5), target size (larger or smaller than 5),
response congruity (whether or not the prime and target fell on
the same side of 5), and repetition (within the congruent trials,
whether or not the prime and target were the same number).
On masked trials, we first presented a randomly chosen
uppercase consonant string for 71 ms, the prime for 43 ms,
another consonant string for 71 ms, and finally the target for 200
ms. On unmasked trials, the same sequence was used, but the
consonant strings were replaced with blank screens (Fig. 1).
Before each trial, a warning signal (a rectangle 10° wide and 6°
high surrounding the stimulus position) appeared with a lag of
one second (training) or two seconds (single-event fMRI).
Procedure. Before fMRI scanning, participants took a behavioral
test with masked primes only. This test consisted of 20 training
trials followed by 128 experimental trials (4 blocks of 32 trials,
plus one initial training trial, which was later discarded). Masked
trials were presented at a 3-s rate on a computer screen (70-Hz
refresh rate). During fMRI scanning, subjects continued with
the masked trials (training, 20 trials; scanning, two blocks of 32
trials plus 1 discarded trial), then were introduced to the
unmasked trials (training, at least one block of 20 trials; scan-
ning, two blocks of 32 trials plus 1 discarded trial). Stimuli were
presented every 14 s through mirror glasses and an active matrix
video projector (70-Hz refresh rate). Stimulus onset was syn-
chronized with the acquisition of the first slice in a series of seven
volumes of 18 slices each. We used a gradient-echo echo-planar
imaging sequence sensitive to brain oxygen-level-dependent
(BOLD) contrast (18 contiguous axial slices, 6-mm thickness,
repetition time兾echo time ⫽ 2,000兾60 ms, field of view 24 cm,
64 ⫻ 64 matrix, voxel size 3.75 ⫻ 3.75 ⫻ 6 mm) on a 1.5-Tesla
whole body system (Signa, General Electric). High-resolution
anatomical images were also acquired by using a 3D fast
gradient-echo inversion-preparation sequence (124 contiguous
axial slices, 1.2-mm thickness, inversion time ⫽ 600 ms, echo
time ⫽ 2.2 ms, field of view 24 cm, 256 ⫻ 192 matrix, voxel size
0.9375 ⫻ 0.9375 ⫻ 1.2 mm).
After scanning, all but four subjects (three controls, one
patient) participated in a forced-choice prime detection task by
using two successive blocks of trials. In block 1, subjects were
presented with a list of 64 masked trials, 16 trials at each of four
prime durations (43, 71, 114, or 200 ms). In block 2, subjects were
presented with 16 randomized unmasked trials, using a 43-ms
prime duration. In both blocks, the prime was omitted on half the
trials, and subjects were asked whether they thought that a prime
was present or absent.
fMRI Analysis. Analysis was done with SPM99 software. The first 7
fMRI volumes of each block, corresponding to the first trial,
were discarded, leaving 224 volumes in each of four blocks.
Images were corrected for subject motion and slice acquisition
delays, normalized to Talairach coordinates by using a linear
transform calculated on the anatomical images, and smoothed.
The signal was modeled as a linear combination, for each subject
and each event type, of a standard haemodynamic response
function and its temporal derivative, thus allowing for different
delays across brain regions. Event types were defined by a
combination of the following factors: response hand, prime-
target relation (congruent repeated, congruent nonrepeated, or
incongruent), notation identity (prime and target in same or
different notation), and masking. Random-effect analyses were
Fig. 1. Experimental paradigm. Subjects compared a 200-ms target number
to a fixed numerical standard. Each target was preceded by a fast presentation
of another number that served as a prime. In different blocks, the prime could
be masked by random consonant strings (Left), or it could be visible and had
to be actively ignored (Right).
Dehaene et al. PNAS
兩
November 11, 2003
兩
vol. 100
兩
no. 23
兩
13723
PSYCHOLOGY
then performed on those factors (voxel P ⫽ 0.01, cluster P ⬍ 0.05
corrected).
Behavioral Results
Number Comparison. We first tested whether patients and controls
differed on number comparison processes through an analysis of
variance (ANOVA) on median response time (RT) with factors
of group, target notation, distance, and size, pooling over all
masked and unmasked trials and over prescanning and scanning
blocks (the results did not differ across those periods). Patients
were overall slower than controls [559 vs. 495 ms, F(1,31) ⫽ 6.20,
P ⫽ 0.018]. However, no interaction was found between group
and any of the variables known to affect number comparison (ref.
39; see Fig. 2). Both groups were slower with verbal notation
than with arabic notation [34-ms notation effect, F(1,31) ⫽
133.87, P ⬍ 0.0001]. Both groups were also affected by a similar
distance effect [32-ms effect, F(1,31) ⫽ 85. 89, P ⬍ 0.0001].
Furthermore, as previously reported (39), a triple interaction of
notation, distance, and size reflected an effect of word length
[slower responses for QUATRE in French, and faster responses
for SIX, only in verbal notation; F(1,31) ⫽ 6.29, P ⫽ 0.018]. No
other interactions were significant.
The error rate was slightly and nonsignificantly higher in
patients than in controls (4.0% vs. 2.7% errors, P ⫽ 0.18). Error
analyses showed effects of distance [2.2% effect, F(1,31) ⫽ 19.59,
P ⫽ 0.0001] and notation [1.1% effect, F(1,31) ⫽ 4.34, P ⫽
0.046], which did not differ across groups. The only interaction
involving group was a small and unexplained group by size
interaction [F(1,31) ⫽ 4.69, P ⫽ 0.038], suggesting that normal
subjects made slightly more errors with larger than with smaller
targets whereas the converse tended to be true of patients. In
summary, despite their overall slower responses, patients showed
normal performance on every measure of the number compar-
ison process.
Masked Priming. We then tested the prediction that patients
should be unimpaired on measures of masked priming and
subliminal motor conflict. This prediction was tested by an
ANOVA on median RT from all masked trials, with factors of
group, prime-target relation (congruent repeated, congruent
nonrepeated, and incongruent), and notation identity (prime
and target in same or in different notation). The main effect of
prime-target relation was significant overall [F(1,31) ⫽ 14.42,
P ⬍ 0.0001] and in each group (controls, P ⫽ 0.0003; patients,
P ⫽ 0.015; Fig. 2). It could be decomposed into two distinct
effects that replicated our earlier results (21–23): response
priming and quantity priming. First, responses were faster on
congruent nonrepeated trials than on incongruent trials [508 vs.
519 ms, t(31) ⫽ 2.95, one-tailed P ⫽ 0.003]. Second, within the
congruent trials, responses tended to be even faster when the
same number was presented as prime and target, than when two
different numbers were presented [502 vs. 508 ms; t(31) ⫽ 1.83,
one-tailed P ⫽ 0.038]. Both effects were unaffected by changes
in number notation. Crucially, there were no interactions with
group. In particular, subliminal response priming was identical
and significant within each group (Fig. 2).
Prime Detection. Behavioral data from the prime detection block,
where subjects performed a present兾absent judgement on the
masked primes, were used to compute a prime detection score
(d⬘) for each of the four masked durations and for the unmasked
43-ms condition. An ANOVA with prime presentation (five
levels) and group (normal subjects and patients) revealed a
progressive improvement with prime duration (43 ms, d⬘⫽0.56;
71 ms, d⬘⫽1.15; 114 ms, d⬘⫽1.39; 200 ms, d⬘⫽2.18; and 43
ms unmasked, d⬘⫽2.74). There was also a main effect of group
(P ⫽ 0.02): the detection of primes was better in controls than
in patients, in agreement with previous studies (40, 41). There
was no duration by group interaction. Even at the duration of 43
ms, which was used during fMRI, prime perception was better
than chance (Z test, P ⬍ 0.0001), and higher in normal subjects
than in patients (d⬘⫽0.88 vs. 0.29, P ⫽ 0.03).
The d⬘ values in normal subjects were higher than in our
previous experiments (21), perhaps due to the use of a different
fMRI setup and video projector. To evaluate whether this small
amount of prime visibility could account for the masked priming
effect in RTs, we used a regression method developed by
Greenwald et al. (42). Using each subject’s mean response time
to masked incongruent and congruent trials (RT
ICG
and RT
CG
),
we computed an individual priming index I ⫽ 100 ⫻ (RT
ICG
⫺
RT
CG
)兾(RT
ICG
⫹ RT
CG
) and correlated it with the individual d⬘
values for 43-ms masked primes. There was no significant
correlation between d⬘ and the amount of priming (P ⫽ 0.75).
Crucially, the priming index at the d⬘⫽0 intercept was signif-
icantly positive (I ⫽ 5.5%, P ⫽ 0.001), suggesting significant
priming in the absence of prime detection. We also conducted
regression analyses separately for controls and patients, with
similar results. Those findings suggest that, although the pres-
ence of masked primes could be partially detected with effort,
masked priming was independent of prime visibility and identical
in both groups.
Comparison of Masked and Unmasked Priming. A final behavioral
analysis tested the prediction that patients are impaired in
conscious conflict control. An ANOVA on median RT from the
fMRI trials (with factors of group, prime-target relation, and
masking) revealed a group by masking interaction [F(1,31) ⫽
7.87, P ⫽ 0.0086]. In normal subjects, the unmasked condition
was slower than the masked condition (34 ms effect, P ⬍ 0.005).
However, this effect was about three times larger in the patients
(93 ms effect, P ⬍ 0.0003), indicating a disproportionately
greater difficulty in controlling interference from an unmasked
prime than from a masked prime.
Furthermore, a triple interaction of group, prime-target re-
lation, and masking [F(2, 62) ⫽ 3.76, P ⫽ 0.029] indicated an
anomalous conscious conflict effect in patients (Fig. 2). As noted
above, there was no group difference on masked priming, but
Fig. 2. Behavioral performance in number comparison in control subjects
and in patients with schizophrenia (mean effect size in milliseconds ⫾ SE).
Both groups show identical effects of numerical distance, number notation,
and subliminal priming. However, they differed in the unmasked priming
effect, which required conscious control of interference. Patients were also
severely slowed in the unmasked condition compared with the masked
condition.
13724
兩
www.pnas.org兾cgi兾doi兾10.1073兾pnas.2235214100 Dehaene et al.
analyses restricted to the unmasked priming condition revealed
a significant group effect [F(2,28) ⫽ 6.17, P ⫽ 0.006]. As
previously described (21), normal subjects were 34 ms slower
when the prime and target were incongruent than when they
were congruent [F(1,17) ⫽ 51.2, P ⬍ 0.0001). Surprisingly, this
effect was absent in patients (effect size ⫺12 ms, F ⬍ 1), creating
a significant interaction with group [F(1,31) ⫽ 7.72, P ⫽ 0.0092].
Even within the unmasked condition, repetition priming itself
was normal. Responses were faster when the prime and target
were the same number [59-ms effect; F(1,31) ⫽ 25.9, P ⬍ 0.0001],
especially when they appeared in the same notation (interaction
F ⫽ 4.00, P ⫽ 0.054), but neither of those effects differed
between groups (P ⬎ 0.20). Together with the normality of the
distance effect, notation effect, and masked priming effect, this
finding suggests that the cognitive impairment in schizophrenia
is rather selectively linked to the anomalous monitoring and
regulation of conscious conflicts.
Error rates were low and no significant differences were
observed between groups or conditions.
Imaging Results. In both patients and controls, a broad network
was activated during task performance relative to the intertrial
resting period. The main areas activated by the number com-
parison task, including bilateral ventral occipito-temporal, in-
traparietal and central sulci (39), were identically activated in
patients and controls. However, several areas showed reduced
activation in patients relative to controls, including the bilateral
ACC, inferior frontal and middle temporal gyri, right superior
frontal and right postcentral gyri, bilateral hippocampus, thal-
amus, and caudate nuclei (Table 1, which is published as
supporting information on the PNAS web site). In particular,
there was no detectable task-induced activity in the most ante-
rior sector of the cingulate (y ⬎ 28, z ⬍ 24) in patients (Fig. 3).
We first tested with normal subjects the predicted engagement
of the ACC in conscious, but not subliminal, control through the
interaction of the congruity effect with masking. A large extent
of the ACC, particularly in the left hemisphere, showed the
predicted effect. There was a greater activation on incongruent
trials than on congruent trials with visible primes, but no such
difference with masked primes (Fig. 4). In addition to the ACC,
conscious but not subliminal conflict also affected activation in
a distributed network including the bilateral inferior frontal gyri,
precunei, superior and middle temporal gyri, striate cortex,
cerebellum, caudate, and putamen, as well as the right central兾
postcentral region (Table 1).
We then contrasted this pattern with that of patients. The
predicted triple interaction of congruity, consciousness, and
group was significant in many of the above regions, including the
left ACC (Fig. 4 and Table 1). This finding reflected a significant
alteration of the responses to conscious conflicts in patients
compared with controls. Contrary to normal subjects, patients
did not show any region with a significant congruity effect to
unmasked trials. The brain oxygen-level-dependent signal in the
left ACC showed both a hypoactivation and an absence of
conflict effect in patients (Fig. 4).
Fig. 3. Reduced overall activation of the anterior cingulate and frontal
cortices, relative to the intertrial resting period, in patients relative to controls.
Fig. 4. Effect of conscious conflict in the anterior cingulate in controls and
in patients. (A Upper) Congruity ⫻ visibility interaction in normal subjects,
showing greater activation in ACC and other brain regions on incongruent
trials than on congruent trials, but only when the prime was unmasked. This
effect was not found in patients, thus resulting in a triple-interaction group ⫻
congruity ⫻ visibility (A Lower). Curves show the mean percent signal change
in the left ACC as a function of time (B), revealing a hypoactivation and an
absence of conscious conflict effect in the patients.
Dehaene et al. PNAS
兩
November 11, 2003
兩
vol. 100
兩
no. 23
兩
13725
PSYCHOLOGY
Discussion
Our experimental results can be summarized as follows: (i) both
masked and unmasked primes induced a behavioral conflict
effect in normal subjects; (ii) the ACC was sensitive to conflict
only when the primes were unmasked; (iii) in patients with
schizophrenia, the ACC was hypoactivated and insensitive to
conflict; and (iv) patients showed normal behavior in number
comparison and masked priming but were disproportionately
slower and showed an absence of conflict when the primes were
unmasked.
The behavioral results in normal subjects replicate our earlier
findings (21–23). Masked numerical primes affect the processing
of a subsequent visible target number in two different ways:
subjects are faster when the target is the same number as the
prime (repetition priming), and when the prime induces the same
response as the target (response priming). Although the latter
effect is due to a conflict between motor activations induced by
the prime and by the target (21), our fMRI results indicate that
it does not yield a detectable activation of the ACC. This finding
suggests that the ACC is not activated mechanically by any motor
conflict but is particularly engaged in the regulation of con-
sciously detected conflicts. This conclusion also fits with previ-
ous experiments that have compared brain activity to subliminal
and supraliminal auditory tones (17) or written words (19). In
those experiments, ACC activation occurred solely in response
to the supraliminal stimuli. As in the present experiment, it was
accompanied by distributed activation in distant areas, including
prefrontal and parietal cortices, consistent with anatomical
studies of a widespread prefrontal network involved in the
cognitive regulation of behavior (43).
We cannot exclude that a subliminal conflict effect was present
in the ACC but could not be detected at a statistically significant
level. Note, however, that, behaviorally, the subliminal congruity
effect was highly significant (P ⬍ 0.0001) and about half the size of
the behavioral conscious congruity effect whereas the ACC acti-
vation curves showed not even a trend toward a difference between
congruent and incongruent masked trials (Fig. 4). We also repli-
cated this absence of a difference between congruent and incon-
gruent trials in the ACC in a reanalysis of our earlier results with
the same masked priming paradigm (21). At a minimum, this result
indicates a highly nonlinear relation between the size of behavioral
conflict effects and the ACC activation, as indicated by a significant
congruity ⫻ masking interaction. There might be a minimal thresh-
old on the amount of conflict needed to trigger ACC activation. The
conscious workspace theory would further predict that this thresh-
old coincides precisely with the threshold for conscious report of the
masked primes. In a future experiment, this could be tested by
continuously varying prime duration while monitoring prime visi-
bility, behavioral priming, and the ACC conflict effect.
Further support for the hypothesis that the ACC and PFC do not
contribute to the management of subliminal conflicts came from
the study of subliminal and supraliminal conflicts in patients with
schizophrenia. Our fMRI results confirm a major hypoactivation of
the ACC in schizophrenia. Consistent with previous functional
imaging findings (29–33) and with the well-documented anatomical
features of such patients (25–28), activation was also reduced at
several other sites, including inferior prefrontal, superior temporal,
and subcortical regions. Despite those anomalies, behavior was
strictly normal in all aspects of number processing and of subliminal
priming. Even within the blocks with conscious primes, repetition
priming was unaffected. This dissociation between impaired ACC-
PFC and intact behavioral forms of priming is consistent with the
finding of normal or even enhanced repetition and semantic
priming effects in schizophrenia (34, 35). Automatic priming effects
are thought to arise within perceptual and semantic posterior
regions such as the visual word form system (19, 23) where
conflicting primes exert a subliminal competition that induces a
measurable delay in response times. Similarly, subliminal response
congruity effects are thought to be caused by competition at the
motor level where incongruent primes induce a small transient
lateralized motor preparation that is subsequently replaced, after a
period of response competition, by the target-induced motor ac-
tivity (21). Both forms of priming, then, seem to be resolved
spontaneously within specialized processors without the need for
global executive control, explaining that they do not cause ACC-
PFC activation and are unaffected by ACC-PFC dysfunction in
schizophrenia.
As predicted, the only behavioral impairments in schizophrenia
were found in the management of conscious conflict induced by the
unmasked primes. First, the patients were disproportionately slow
in blocks with unmasked primes, suggesting that their pathology
interferes with the filtering-out of the irrelevant primes and兾or the
management of the interference that they induce. Indeed, our study
comprised mostly stabilized patients with marked negative symp-
toms, who are known to often exhibit a general slowness in higher
cognitive tasks (44). Second, surprisingly, our patients showed a
significantly smaller conscious conflict effect than control subjects.
In fMRI, this finding was accompanied by a generalized hypoac-
tivation of anterior ACC and PFC (Fig. 4) and by an absence of a
differential activation on conscious congruent vs. incongruent
trials. A similar lack of mobilization of ACC and PFC in schizo-
phrenia, in proportion to the executive demands of the task, was
reported in other paradigms, such as random number generation or
the Stroop task (30–32).
Our behavioral result departs from the classical finding that
schizophrenia is associated with a greater number of errors in
Stroop interference trials (31), although not always with a larger
interference effect in response times (45, 46). One possibility is that
the patients were globally slower, thus allowing for a spontaneous
dissipation of the prime-induced motor interference effects and its
replacement by target-induced activation. Another possibility is
that unmasking the primes created new unforeseen sources of
interference, including a tendency to compare the target number
with the prime rather than with the memorized number 5. Such an
additional interference effect may have overridden the motor
congruity effect, resulting in a paradoxical reduction of this effect
in the patients’ behavioral results.
The observed dissociation between preserved automatic sub-
liminal processing and impaired conscious control fits with
several similar observations of a selective failure of conscious
appraisal in schizophrenia. For instance, patients with schizo-
phrenia experience a reduced perception of masked stimuli (40,
41), as replicated in our d⬘ measurements. Interestingly, only
backward masking is impaired whereas forward masking, which
is thought to be based on retinal and cortical bottom-up mech-
anisms, remains intact (41). Patients with schizophrenia also
exhibit a dissociation between impaired explicit recollection and
normal implicit memory (36–38). Together with evidence for
impaired awareness of self-generated action (47), those results
converge to suggest that a core deficit in schizophrenia concerns
a distributed cortical conscious monitoring system that involves
the ACC as a crucial node (48, 49).
1. Paus, T., Koski, L., Caramanos, Z. & Westbury, C. (1998) NeuroReport 9,
R37–R47.
2. Bush, G., Luu, P. & Posner, M. I. (2000) Trends Cogn. Sci. 4, 215–222.
3. Botvinick, M., Nystrom, L. E., Fissell, K., Carter, C. S. & Cohen, J. D. (1999)
Nature 402, 179–181.
4. Cohen, J. D., Botvinick, M. & Carter, C. S. (2000) Nat. Neurosci. 3, 421– 423.
5. Carter, C. S., Macdonald, A. M., Botvinick, M., Ross, L. L., Stenger, V. A., Noll,
D. & Cohen, J. D. (2000) Proc. Natl. Acad. Sci. USA 97, 1944–1948.
6. MacDonald, A. W., 3rd, Cohen, J. D., Stenger, V. A. & Carter, C. S. (2000)
Science 288, 1835–1838.
7. Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S. & Cohen, J. D.
(2001) Psychol. Rev. 108, 624–652.
13726
兩
www.pnas.org兾cgi兾doi兾10.1073兾pnas.2235214100 Dehaene et al.
8. Dehaene, S., Posner, M. I. & Tucker, D. M. (1994) Psychol. Sci. 5, 303–305.
9. Carter, C. S., Braver, T. S., Barch, D., Botvinick, M. M., Noll, D. & Cohen, J. D.
(1998) Science 280, 747–749.
10. Posner, M. I. & Rothbart, M. K. (1998) Philos. Trans. R. Soc. London B Biol.
Sci. 353, 1915–1927.
11. Posner, M. I. (1994) Proc. Natl. Acad. Sci. USA 91, 7398–7403.
12. Dehaene, S., Kerszberg, M. & Changeux, J. P. (1998) Proc. Natl. Acad. Sci. USA
95, 14529–14534.
13. Dehaene, S. & Naccache, L. (2001) Cognition 79, 1–37.
14. Dehaene, S., Sergent, C. & Changeux, J. P. (2003) Proc. Natl. Acad. Sci. USA
100, 8520–8525.
15. Bush, G., Vogt, B. A., Holmes, J., Dale, A. M., Greve, D., Jenike, M. A. &
Rosen, B. R. (2002) Proc. Natl. Acad. Sci. USA 99, 523–528.
16. Holroyd, C. B. & Coles, M. G. (2002) Psychol. Rev. 109, 679–709.
17. Stephan, K. M., Thaut, M. H., Wunderlich, G., Schicks, W., Tian, B., Tellmann,
L., Schmitz, T., Herzog, H., McIntosh, G. C., Seitz, R. J. & Homberg, V. (2002)
NeuroImage 15, 345–352.
18. Laureys, S., Faymonville, M. E., Luxen, A., Lamy, M., Franck, G. & Maquet,
P. (2000) Lancet 355, 1790–1791.
19. Dehaene, S., Naccache, L., Cohen, L., Le Bihan, D., Mangin, J. F., Poline, J. B.
& Rivicˇre, D. (2001) Nat. Neurosci. 4, 752–758.
20. Portas, C. M., Krakow, K., Allen, P., Josephs, O., Armony, J. L. & Frith, C. D.
(2000) Neuron 28, 991–999.
21. Dehaene, S., Naccache, L., Le Clec’H, G., Koechlin, E., Mueller, M., Dehaene-
Lambertz, G., van de Moortele, P. F. & Le Bihan, D. (1998) Nature 395,
597–600.
22. Naccache, L. & Dehaene, S. (2001) Cognition 80, 215–229.
23. Naccache, L. & Dehaene, S. (2001) Cereb. Cortex 11, 966–974.
24. Benes, F. M., Vincent, S. L. & Todtenkopf, M. (2001) Biol. Psychiatry 50,
395–406.
25. Szeszko, P. R., Bilder, R. M., Lencz, T., Ashtari, M., Goldman, R. S., Reiter,
G., Wu, H. & Lieberman, J. A. (2000) Schizophr. Res. 43, 97–108.
26. Sigmundsson, T., Suckling, J., Maier, M., Williams, S., Bullmore, E., Green-
wood, K., Fukuda, R., Ron, M. & Toone, B. (2001) Am. J. Psychiatry 158,
234–243.
27. Paillere-Martinot, M., Caclin, A., Artiges, E., Poline, J., Joliot, M., Mallet, L.,
Recasens, C., Attar-Levy, D. & Martinot, J. (2001) Schizophr. Res. 50, 19–26.
28. Suzuki, M., Nohara, S., Hagino, H., Kurokawa, K., Yotsutsuji, T., Kawasaki, Y.,
Takahashi, T., Matsui, M., Watanabe, N., Seto, H. & Kurachi, M. (2002)
Schizophr. Res. 55, 41–54.
29. Andreasen, N. C., O’Leary, D. S., Flaum, M., Nopoulos, P., Watkins, G. L.,
Boles Ponto, L. L. & Hichwa, R. D. (1997) Lancet 349, 1730–1734.
30. Artiges, E., Salame, P., Recasens, C., Poline, J. B., Attar-Levy, D., De La
Raillere, A., Paillere-Martinot, M. L., Danion, J. M. & Martinot, J. L. (2000)
Am. J. Psychiatry 157, 1517–1519.
31. Carter, C. S., Mintun, M., Nichols, T. & Cohen, J. D. (1997) Am. J. Psychiatry
154, 1670–1675.
32. Carter, C. S., MacDonald, A. W., 3rd, Ross, L. L. & Stenger, V. A. (2001) Am.
J. Psychiatry 158, 1423–1428.
33. Meyer-Lindenberg, A., Poline, J. B., Kohn, P. D., Holt, J. L., Egan, M. F.,
Weinberger, D. R. & Berman, K. F. (2001) Am. J. Psychiatry 158, 1809–1817.
34. Minzenberg, M. J., Ober, B. A. & Vinogradov, S. (2002) J. Int. Neuropsychol.
Soc. 8, 699–720.
35. Hoschel, K. & Irle, E. (2001) Schizophr. Bull. 27, 317–327.
36. Huron, C., Danion, J. M., Giacomoni, F., Grange, D., Robert, P. & Rizzo, L.
(1995) Am. J. Psychiatry 152, 1737–1742.
37. Kazes, M., Berthet, L., Danion, J. M., Amado, I., Willard, D., Robert, P. &
Poirier, M. F. (1999) Neuropsychology 13, 54–61.
38. Danion, J. M., Meulemans, T., Kauffmann-Muller, F. & Vermaat, H. (2001)
Am. J. Psychiatry 158, 944–948.
39. Dehaene, S. (1996) J. Cognit. Neurosci. 8, 47–68.
40. Green, M. F., Nuechterlein, K. H., Breitmeyer, B. & Mintz, J. (1999) Am. J.
Psychiatry 156, 1367–1373.
41. Saccuzzo, D. S., Cadenhead, K. S. & Braff, D. L. (1996) Am. J. Psychiatry 153,
1564–1570.
42. Greenwald, A. G., Draine, S. C. & Abrams, R. L. (1996) Science 273,
1699–1702.
43. Goldman-Rakic, P. S. (1988) Annu. Rev. Neurosci. 11, 137–156.
44. Salame, P., Danion, J. M., Peretti, S. & Cuervo, C. (1998) Schizophr. Res. 30,
11–29.
45. Chen, E. Y., Wong, A. W., Chen, R. Y. & Au, J. W. (2001) Schizophr. Res. 48,
29–44.
46. Barch, D. M., Carter, C. S., Hachten, P. C., Usher, M. & Cohen, J. D. (1999)
Schizophr. Bull. 25, 749–762.
47. Franck, N., Farrer, C., Georgieff, N., Marie-Cardine, M., Dalery, J., d’Amato,
T. & Jeannerod, M. (2001) Am. J. Psychiatry 158, 454–459.
48. Frith, C. D., Blakemore, S. & Wolpert, D. M. (2000) Brain Res. Brain Res. Rev.
31, 357–363.
49. Fletcher, P., McKenna, P. J., Friston, K. J., Frith, C. D. & Dolan, R. J. (1999)
NeuroImage 9, 337–342.
Dehaene et al. PNAS
兩
November 11, 2003
兩
vol. 100
兩
no. 23
兩
13727
PSYCHOLOGY