Download Neural correlates of incidental and directed facial emotion

doi:10.1093/scan/nsp029
SCAN (2009) 4, 387–398
Neural correlates of incidental and directed facial
emotion processing in adolescents and adults
Alessandra M. Passarotti,1,2 John A. Sweeney,2 and Mani N. Pavuluri1,2
1
Institute for Juvenile Research, and 2Center for Cognitive Medicine, Department of Psychiatry, University of Illinois at Chicago, Chicago,
IL, USA
Keywords: functional magnetic resonance imaging (fMRI); face emotion; emotion; incidental; development; adolescent
INTRODUCTION
A developmental milestone for social communication and
interactions is the ability to regulate one’s own emotional
reactions in order to produce socially appropriate behaviors
(Adolphs, 2002; Bell and Deater-Deckard, 2007). There is
some consensus on the view that better emotional selfregulation in late adolescence and adulthood may result
from improved executive functions and cognitive control
over affect processes (Posner and Rothbart, 2000; Monk
et al., 2003; Nelson et al., 2005; Blakemore 2008). In fact,
recent studies have suggested that while in adolescents brain
activity is more driven by the emotional content of stimuli,
in adults it is more attention- and goal-driven (Monk et al.,
2003), although more experimental evidence is needed in
this regard.
From a developmental science perspective, it is fundamental to study adolescence because it is a crucial transition time
for maturation and reorganization of cognitive, affective and
social functions (Spear, 2000; Casey et al., 2008). Moreover,
because of this developmental reorganization, adolescents,
compared with adults, often exhibit greater emotional reactivity, which may put them at risk for hazardous behavior
and increased vulnerability to mood and anxiety disorders
Received 20 January 2009; Accepted 16 July 2009
This work is supported by National Institute of Health K23 RR18638-01, Marshall Reynolds Foundation, and
University of Illinois at Chicago Magnetic Resonance Center for Research Pilot Fund.
Correspondence should be addressed to Alessandra M. Passarotti, Center for Cognitive Medicine, Institute
for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, 912 South Wood Street
(M/C 913), Chicago, IL 60612, USA. E-mail: [email protected].
(Nelson et al., 2005; Blakemore, 2008; Casey et al., 2008).
It has, in fact, been suggested that abnormal development of
affect regulation functions may be intrinsic to pediatric
bipolar disorder (Pavuluri et al., 2006; Pavuluri and
Passarotti, 2008), anxiety disorders (Thomas et al., 2001),
child depression (Silk et al., 2006) and autism (Davidson
and Slagter, 2000). Therefore, it is crucial to elucidate the
neurodevelopmental trajectory of the underlying brain
systems in healthy child and adolescent populations, also
to be able to accurately characterize the deviance from
normal development of affect regulation and social behavior
in such clinical populations.
To this aim, Nelson et al. (2005) propose a developmental
model of social information processing in terms of a neural
network that has three interactive neural nodes, each with
different functions and developmental timetables. A ‘detection’ node (composed of intraparietal sulcus, superior
temporal sulcus and inferior temporal and occipital regions)
detects socially relevant stimuli and matures in the first few
years of life. An ‘affective’ node processes the emotional
significance of detected social stimuli, and includes regions
engaged by reward and punishment (i.e. amygdala and
other limbic regions, ventral striatum, hypothalamus and
in certain circumstances orbitofrontal cortex), which are
primary sites of gonadal steroids and hormonal action.
They also undergo functional and anatomical reorganization
during puberty due to surge of gonadal hormones by regulation of other neurotransmitter systems (Giedd et al., 1996).
Developmental studies suggest that the amygdala is fairly
functional in processing emotions since the first few years
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Our knowledge on the development of the affective and cognitive circuitries that underlie affect regulation is still limited.
This functional magnetic resonance imaging (fMRI) study examined whether there is more efficient prefrontal modulation of
affective circuits with development. Ten adolescents (mean age 14 2 years) and 10 adults (mean age 30 6 years) underwent
two scanning conditions that required different levels of cognitive control over face emotion processing. A ‘directed’ emotion
processing condition required judgment of facial expressions. An ‘incidental’ emotion processing condition required an age
judgment. For the incidental emotion processing condition, adolescents, compared with adults, showed less activation in right
ventrolateral prefrontal cortex (VLPFC) and greater activation in paralimbic regions, suggesting greater emotional reactivity and
immature prefrontal circuitries for affect regulation. For the directed emotion processing condition, adolescents, compared with
adults, showed decreased recruitment of both the dorsal and pregenual right anterior cingulate cortex (ACC), suggesting
immature modulatory functions of the ACC during directed face emotion processing. These results indicate that the neural
circuitries for affect regulation are still developing in adolescence and have not yet reached the adult level.
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at fearful faces, with development. Abnormal brain maturation during adolescence may affect development of these
three nodes, with consequent dysregulation in their interactions that may increase vulnerability to mood and anxiety
disorders in adolescence (Nelson et al., 2005).
One way to test whether an increase in prefrontal regulation of sub-cortical activity is a possible bio-behavioral
mechanism for the development of emotion regulation and
control functions (Blumberg et al., 2004; Nelson et al., 2005;
Marsh et al., 2006; Bell and Deater-Deckard, 2007; YurgelunTodd, 2007) is to compare brain activation in adolescents
and adults when emotion processing is unconstrained as
compared with when it is under cognitive control. Studies
in healthy adults (Critchley et al., 2000; Hariri et al., 2000;
Gorno-Tempini et al., 2001) and patient populations with
emotional dysregulation (Chen et al., 2006; Pavuluri et al.,
2009) have examined the level of engagement of corticolimbic circuitry during incidental or directed processing of
emotions. In adults, a directed face emotion processing condition (which requires explicit judgment of facial emotions)
tends to elicit the concerted interaction of cortical and limbic
structures, with the VLPFC and ACC directly regulating
amygdala activity (Gorno-Tempini et al., 2001). On the
other hand, the incidental condition, which usually requires
subjects to attend to non-emotional face aspects (e.g. gender
or age) (Gur et al, 2002), is usually characterized by an
automatic increase in amygdalar reactivity in response
to the emotional content of faces (Hariri et al., 2000;
Gorno-Tempini et al., 2001), while the prefrontal cortex
(PFC) attends to non-emotional aspects. Therefore, this condition has been used to more selectively probe sub-cortical
reactivity. Studies with healthy adults (Critchley et al., 2000;
Hariri et al., 2000; Keightley et al., 2003) have reported
greater amygdala activation during incidental than during
directed face emotion processing, which has been explained
in terms of greater automatic affective response of the amygdala when the PFC is not directly modulating emotion processing. Finally, a developmental fMRI study by Monk et al.
(2003) found that during unconstrained attention, adolescents engaged limbic regions more than adults, but only
adults showed differential activation of the OFC when
attending to emotional as compared with non-emotional
face aspects. These developmental findings are in agreement
with Nelson’s model (Nelson et al., 2005) and suggest that
while brain activity is relatively more emotionally driven in
adolescents, with development it becomes more attentionand goal driven (Monk et al., 2003; Nelson et al., 2005).
Building from previous developmental work (Monk et al.,
2003), the present developmental fMRI study is one of the
first to compare brain activation for incidental and directed
face emotion processing in 12- to 18-year-old adolescents
with that of adults, and to investigate whether improved
affect regulation with age is associated with greater PFC
control of activity in sub-cortical emotion circuitries.
Our participants underwent two task conditions. A ‘directed’
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of life (Johnson, 2005), although at least one study found
volumetric changes in the amygdala of 4- to 18-year-old
males (Giedd et al., 1996), which may be associated with
ongoing functional maturation. Moreover, these regions
modulate cognitive processes by driving attention towards
socially relevant stimuli. The ‘cognitive-regulatory’ node
controls impulse inhibition and goal-directed behavior and
consists of dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and orbitofrontal cortex
(OFC). The VLPFC and dorsal anterior cingulate cortex
(dACC) are considered to be a neural interface between
cognitive and affective processes (Petrides and Pandya,
2002; Pavuluri et al., 2007; Pavuluri and Passarotti, 2008).
The VLPFC is involved in inhibition processes (Kemmotzu
et al., 2005), and it also modulates amygdala emotional reactivity via the rostral portion of the ACC (Petrides and
Pandya, 2002; Pavuluri et al., 2007). Moreover, the VLPFC
has direct connections with the DLPFC, which is involved in
cognitive control, working memory and executive functions
(MacDonald et al., 2000) so that interactions between
VLPFC and DLPFC enable goal-directed behavior and emotion regulation. The VLPFC (Gogtay et al., 2004; Marsh
et al., 2006), ACC (Conel, 1967), DLPFC (Giedd, 2004)
and amygdalo-cortical connectivity (Blumberg et al., 2004)
develop more slowly than regions in the other two nodes,
mainly through protracted myelination, synaptic pruning,
maturation and learning, throughout adolescence (Giedd
et al., 1999; Sowell et al., 1999). Their maturation has been
associated with improvements in executive functions (Luna
et al., 2001, 2004; McGivern et al., 2002) and in cognitive
modulation of emotion processing (Blakemore and
Choudhury, 2006).
While these three nodes always interact with each other,
the nature of these interactions changes with development.
While emotion circuits drive attention to socially relevant
stimuli early on, the cognitive regulatory node modulates
emotional circuit activity more and more with maturation
(Nelson et al., 2005). Studies with primates (Goldman-Rakic,
1987), humans with brain damage (Manes et al., 2002) and
healthy individuals (Iidaka et al., 2001; Hariri et al., 2000;
Pavuluri et al., 2006) have confirmed that the brain systems
involved in affect processing and regulation are functionally
and anatomically interconnected, and that with age there is
an increased cognitive control of affect functions (YurgelunTodd, 2007). Recent functional magnetic resonance imaging
(fMRI) studies have found that adolescents exhibit greater
amygdala activation than adults while processing affective
faces (Monk et al., 2003; Guyer et al., 2008; Hare et al.,
2008), although at least a few studies did not find this age
difference in amygdala functioning (Pine et al., 2001; Nelson
et al., 2003). Moreover, Yurgelun-Todd and Killgore (2006)
found increased prefrontal activity while processing fearful
faces in adolescence compared with childhood, and Killgore
et al. (2001) found increased prefrontal activity and
decreased amygdala activity in female subjects while looking
A. M. Passarotti et al.
Facial emotion processing in adolescents
METHODS
Subjects
Our participants were healthy volunteers recruited from
the University of Illinois at Chicago University of Illinois
at Chicago (UIC) and from the surrounding community
through word-of-mouth. They were all right-handed as
assessed by the Annett Handedness Questionnaire (Annett,
1970), and had normal or corrected-to-normal vision. The
WASH-U-KSADS was also administered to all participants
to ensure the absence of any mental disorder. Subjects were
excluded from this study if they had an estimated IQ below a
score of 85. All subjects had comparable IQ scores, as estimated with the Wechsler Abbreviated Scale of Intelligence
(WASI, 1999). Moreover, subjects were excluded if they had
a pervasive developmental disorder, neurological condition,
history of head trauma with loss of consciousness for
>10 min, substance use or mood disorder, use of medication
that would alter cerebral blood flow (such as medication for
migraine and blood pressure) or the presence of metallic
implants, retractors or braces. The study was approved by
the institutional review board at UIC. According to
University IRB protocols, we obtained an informed consent
from all adult subjects. Adolescent participants gave their
assent, and an informed consent was also obtained from at
least one parent or guardian.
389
Out of the initial pool of 13 adult subjects, fMRI data
from three subjects were discarded due to head motion
artifacts. The remaining 10 subjects (five females) had a
mean age of 30 6 years. Neuroimaging data were collected
on 14 healthy adolescents, and data from four of these
subjects were excluded due to excessive head motion. The
remaining 10 individuals (five females) had a mean age of
14 2 years, and were matched on race and gender to the
adult group. There were no significant differences in the
gender (Fisher’s P ¼ 1; NS) and racial (Fisher’s P ¼ 0.65;
NS) composition of the two groups.
fMRI session and directed and incidental emotion
processing tasks
The fMRI task, which lasted for 7 min, consisted of an
incidental and a directed face emotion processing condition.
During the incidental face processing condition, participants
judged whether the presented face was older or younger than
35 years of age. During the directed face processing
condition, participants judged whether the facial affect was
positive/happy or negative/angry. In both conditions, every
face stimulus presented had a facial expression (i.e. angry or
happy) so that face stimuli had the same perceptual and
emotional information in both conditions, and only task
instructions differed across conditions. Responses were by
button press, with the correct response key (i.e. left
or right key) counterbalanced across subjects and equally
randomized across trials.
We used 24 happy and 24 angry faces from a database
of 200 Gur faces, with established reliability and validity
(Gur et al., 2002). The level of emotionality for happy and
angry faces was comparable in the two task conditions based
on normative data provided by Gur et al. (2002). Half of the
faces from each emotion type were older and half younger
than 35 years of age. Correct responses for type of face emotion and age were based on the normative data by Gur et al.
(2002). Faces from this database were also randomly selected
with regard to gender, valence and race (Gur et al., 2002).
Each face was presented on a black background, necks and
shoulders were removed, but hair was left in the images.
Three angry and three happy face trials were presented
in a pseudo-random order in each block of the conditions.
We used the rule that the same trial type (e.g. angry face, or
face >35 years of age) could not be presented more than
twice in a row. Individual faces were not repeated during
the task to avoid effects of repetition and familiarity.
Prior to imaging studies, participants spent 20 min in
a mock scanner to acclimate them to the scanner
environment. Then the scanning session started. A color
high-resolution LCD projector projected visual stimuli
onto a rear projection screen that was viewed via an
angled double-mirror system mounted on a standard GE
head coil. During the scan, a camera monitored subject’s
right eye to ensure attention to visual stimuli. We adopted
a standard block design to maximize signal-to-noise ratio for
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face emotion processing condition required an explicit
judgment on whether a face looks happy or angry, and an
‘incidental’ face emotion processing condition required a
decision on whether the emotional face presented is younger
or older than 35 years (Gur et al., 2002).
Based on previous adult (Critchley et al., 2000; Hariri
et al., 2000; Gorno-Tempini et al., 2001) and developmental
studies (Killgore et al., 2001; Monk et al., 2003; YurgelunTodd, 2007; Guyer et al., 2008; Hare et al., 2008) and on
Nelson’s model (Nelson et al., 2005), we hypothesized that:
(i) for the incidental condition adolescents, compared with
adults, would exhibit greater automatic sub-cortical emotional reactivity during incidental emotion processing,
accompanied by reduced activity in VLPFC due to cortical
and corticolimbic connection immaturity; (ii) for the directed condition adolescents, compared with adults, would
exhibit higher or comparable levels of amygdala activation
during voluntary processing of face emotions, and reduced
engagement of regions that evaluate and regulate emotion
processing, such as the VLPFC and the ACC; and (iii) while
in adults cortical activity would be more modulated by
cognitive goals (i.e. attend to emotions or to age), in adolescents it would be more modulated by automatic emotion
processing. Therefore, we predicted that while for adults
engagement of cortical regions involved in regulation and
evaluation of face emotions (i.e. VLPFC, ACC) would
be more prominent in the directed than in the incidental
condition, the opposite pattern would be present in
adolescents.
SCAN (2009)
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short imaging sessions. The task consisted of four 30-s blocks
of the incidental emotion processing condition (I) and four
30-s blocks of the directed emotion processing condition (D)
(Figure 1). Condition blocks were separated by a 20-s
fixation block (F), with the last 3 s of this period alerting
the subjects on the condition block (i.e. directed or incidental) that would be presented next. For all subjects, blocks
were presented in the following order: (F) I (F) D (F) I (F)
D (F) I (F) D (F) I (F) D (F). On each trial, a face portraying
a happy or angry expression was presented for 5 s. There
were six trials in each block, for a total of 48 trials. Since
processing of face emotions is more automatic than making
an age decision, participants always started with the incidental condition first, in order to avoid that they may carry
over explicit face emotion processing strategies from the
directed condition onto the implicit condition at the
beginning.
Image acquisition, processing and data analysis
MRI acquisitions were performed using a 3.0 T whole body
scanner (Signa, General Electric Medical System, Milwaukee,
WI, USA). Functional images were acquired using gradientecho echo-planar imaging, which is sensitive to regional
alterations in blood flow via blood oxygenation leveldependent (BOLD) contrast effects. Twenty-five axial slices
were acquired. Parameters for functional scans were:
TE ¼ 25 ms; flip angle ¼ 908; field of view ¼ 20 20 cm2;
acquisition matrix ¼ 64 64; TR ¼ 2.5 s; 5 mm slice thickness, with 1 mm gap. Anatomical images were acquired in
the axial plane [3D gradient recalled (SPGR), 1.5 mm thick
contiguous axial slices] and were later co-registered with the
functional data for each subject.
FIASCO software (Functional Imaging Analysis SoftwareComputational Olio; http://www.stat.cmu.edu/fiasco/)
(Eddy et al., 1996) was used to estimate and correct the
functional neuroimaging data for head motion. This
approach implements both 3D motion estimation and
correction, and reduction of cardiac and respiratory effects
in k-space. FIASCO also applies a cubic function to remove
slow signal drift. It provides diagnostics for identifying
images with artifacts such as high shot noise and displacement that cannot be readily corrected by motion correction
algorithms (Eddy et al., 1996). We excluded from the
analyses individual volumes from the time series if head
displacement from the median head position in the time
series was >1.5 mm, or if head rotation from the median
head position was >0.58. The mean number of volumes
excluded from analyses for motion artifact (adolescents:
mean ¼ 64, s.d. ¼ 10.37; adults: mean ¼ 58, s.d. ¼ 22.33)
did not differ significantly across groups [F(1,18) ¼ 0.61;
P < 0.44].
Voxel-wise effect size (r) maps were calculated for each
subject for each pair-wise condition contrast (incidental condition vs fixation, directed condition vs fixation, incidental vs
directed condition), and then a Fisher z-transform was performed voxel by voxel to normalize the data (zr) (Rosenthal,
1991). AFNI software (Analysis of Functional Neuroimages)
(Cox, 1996) was used to transform individual subjects’
zr-maps (effect size) and SPGR anatomical images into
Talairach space using AFNI’s automated Talairach
procedure (Talairach and Tournoux, 1988). Finally we
re-sampled the original functional maps (3.125 3.125 6 mm grid) to an isotropic 3 3 3 mm grid.
In order to examine the group differences in neural
activation for the incidental and directed condition, a
whole brain, voxel-wise omnibus Analysis of Variance
(ANOVA) was carried out in AFNI, with the betweensubjects factor of group (adolescents, adults) and the
within-subjects factor of condition (incidental vs fixation,
directed vs fixation, incidental vs directed). The significant
interaction of group by condition was further examined
through planned t-tests, which were part of the ANOVA.
To correct for multiple voxel-by-voxel comparisons, significant clusters of activation were identified using a contiguity threshold (minimum volume threshold ¼ 270 mm3;
minimum clustering radius: 3.1 mm) applied to the entire
brain, which maintained an experiment-wise Type I error
rate of a corrected P < 0.025, based on AFNI’s AlphaSim
Monte Carlo simulations (Ward, 2000) that were restricted
to in-brain voxels.
In addition, based on findings from the whole brain
ANOVA, we performed Region of Interest (ROI) analyses
so that we could: (i) perform correlation analyses to
determine the relationship between fMRI activation in
specific ROIs and behavioral performance (RT, accuracy)
or age for the two conditions in each group; and (ii) so
that we could quantify and illustrate the significant group
by condition interaction for selected ROIs that showed
group differences in our two conditions. Anatomical ROIs
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Fig. 1 (A) Incidental and directed conditions block design. (B) Examples of face
stimulus displays used for the incidental condition (on the left) and for the directed
condition (on the right).
A. M. Passarotti et al.
Facial emotion processing in adolescents
SCAN (2009)
were defined in standard Talairach space using AFNI tools.
These regions in AFNI format as well as the rationale for
anatomical ROI definition are available at http://ccm
.psych.uic.edu/Research/NormalBrain/ROI_rules.htm;
http://ccm.psych.uic.edu/Research/ResearchProgram/
NormalBrain/ROIaffect_rules.aspx.
fMRI data
A significant group by condition interaction [F(1,18) ¼ 5.04,
P < 0.01] was further explored with planned comparisons
within the ANOVA, for which we corrected for multiple
comparisons and applied cluster thresholding procedures
that ensured an experiment-wise Type 1 error rate of
P < 0.025 (corrected) (see Methods section).
Incidental vs directed condition in each group
Table 2 illustrates significant findings for the comparison
between the two conditions in each group.
Table 1 Response time and accuracy measures for adults and adolescents
on the incidental and directed emotion processing tasks
Response time (ms)
Incidental condition
Directed condition
Accuracy (%)
Incidental condition
Directed condition
Adults
Median s.d.
Adolescents
Median s.d.
1568.2 354.9
1223.7 257.5
1609.8 372.8
1320.3 358.8
80
92
75
83
Adolescent group. Adolescents exhibited greater activation for the incidental than for the directed condition in
right PFC regions, such as the right superior frontal gyrus,
DLPFC and VLPFC, in right dorsal ACC, parahippocampal
gyrus and caudate. They exhibited greater activation for the
directed than the incidental condition in bilateral superior
temporal gyrus and in left inferior parietal lobule.
Adult group. Adults exhibited greater activation for
the incidental than the directed condition in right DLPFC.
They showed greater activation for the directed than the
incidental condition in bilateral VLPFC and medial frontal
gyrus, cingulate regions (left pregenual ACC, mid-cingulate
cortex and bilateral posterior cingulate cortex) and temporoparietal regions (bilateral middle temporal gyrus and left
inferior parietal lobule).
Group differences for incidental vs directed condition
Table 3 provides a list of significant group differences for the
incidental vs directed condition.
The adolescent group showed greater activation than
the adult group for the incidental relative to the directed
condition in right DLPFC and VLPFC, dorsal ACC, posterior cingulate and inferior parietal lobule, bilateral middle
temporal gyrus and precuneus. Adolescents showed less
activation than adults in no brain region.
Group differences for incidental or directed condition
vs fixation
Table 4 provides a list of significant group differences for
each condition compared with fixation. Figure 2 illustrates
significant group differences in brain activation in selected
ROIs, and relative bar graphs of functional activation for
the significant interaction of group by condition.
Incidental condition. The adolescent group showed
greater activation than the adult group for the incidental
condition in right DLPFC/middle frontal gyrus (Figure 2A
and B), right medial PFC and mid-cingulate gyrus, left
precuneus and bilateral posterior cingulate gyrus, posterior
face processing regions (right fusiform gyrus, bilateral
middle temporal gyrus) and bilateral parahippocampal
gyrus. Adults showed greater activation than adolescents
for the incidental condition in right VLPFC (Figure 2C
and D). Finally, compared with adults, adolescents exhibited
greater right amygdala activation (Figure 2E and F), but only
with a more liberal contiguity threshold, i.e. corrected
P < 0.05, than that applied to the whole-brain analysis
(i.e. corrected P < 0.025).
Directed condition. The adolescent group showed
greater activation than the adult group for the directed
condition in right fusiform gyrus. Adults showed greater
activation than adolescents in right pregenual ACC, bilateral
dorsal ACC (Figure 2G and H) left caudate and left middle
temporal gyrus.
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RESULTS
Behavioral data
Median RT and accuracy data were analyzed in separate
repeated measures ANOVAs. Group (adolescents, adults)
was the between-subjects factor, and Condition (Incidental,
Directed) was the within-subjects factor. Median RT (for
correct responses) and accuracy data for each group and
each condition are summarized in Table 1. With regard to
median RT, no significant effects or interactions were found.
There was only a non-significant trend for condition
[F(1,18) ¼ 132.9; P ¼ 0.06], in that across groups median
RT was faster for the directed (1272 ms) than for the incidental face emotion processing (1589 ms) condition.
The accuracy data revealed higher accuracy for the directed
(87%) than for the incidental (78%) condition across groups
[F(1,18) ¼ 17.07, P < 0.0007], but there were no significant
effects of group [F(1,18) ¼ 0.26, P < 0.62] or group by
condition [F(1,18) ¼ 2.15, P < 0.16]. Finally, the difference
in accuracy between the directed and the incidental condition did not differ significantly in the two groups
[F(1,18) ¼ 0.93, P < 0.35] (there was an 8% difference in
accuracy between the two conditions for the adolescent
group, and a 12% difference in accuracy between the two
conditions for the adult group).
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A. M. Passarotti et al.
Table 2 Incidental vs directed condition for each group
Adolescents
Incidental > directed
Directed > incidental
t-value for peak activation
BA 22
BA 22
BA 40
1512
1782
486
3159
324
378
297
810
729
270
3.08
3.50
4.29
3.90
3.22
3.04
2.88
3.88
5.23
3.15
BA
BA
BA
BA
BA
BA
BA
BA
BA
BA
BA
BA
1188
1809
1728
270
459
1053
1647
1377
405
4914
2835
2619
4.54
3.16
3.01
2.57
3.24
4.66
3.08
5.15
3.13
5.08
4.24
4.92
Region
BA
32, 56, 14
44, 38, 20
26, 32, 7
5, 21, 39
8, 20, 11
38, 49, 4
22, 7, 2
59, 43, 8
64, 28, 11
58, 46, 38
Right superior frontal gyrus
Right middle frontal gyrus
Right inferior frontal gyrus
Right dorsal ACC
Right caudate
Right parahippocampal gyrus
Left parahippocampal gyrus
Right superior TG
Left superior TG
Left inferior parietal lobule
BA
BA
BA
BA
44, 38, 23
11, 50, 8
1, 56, 2
53, 29, 2
49, 23, 8
7, 29, 11
1, 13, 38
14, 52, 32
16, 61, 20
59, 52, 8
55, 64, 5
52, 34, 29
Right middle frontal gyrus
Right medial frontal gyrus
Left medial frontal gyrus
Right inferior frontal gyrus
Left inferior frontal gyrus
Left pregenual ACC
Left mid-CG
Right posterior CG
Left posterior CG
Right middle TG
Left middle TG
Left inferior parietal lobule
10
46
47
32
46
10
10
45
45
24
24
31
31
22
37
40
Talairach coordinates and t-values for peak activation in significant clusters (P < 0.025 with contiguity threshold; minimum volume threshold ¼ 270 mm3) representing greater
activation in each group for one condition relative to the other. CG, cingulate gyrus; TG, temporal gyrus.
Table 3 Incidental vs directed condition for adolescents vs adults
Adolescents > adults
Incidental vs directed
Adults > adolescents
Incidental vs directed
None
Talairach coordinates for peak values
Region
BA
5, 47, 26
13, 62, 17
26, 32, 7
11, 26, 32
53, 49, 1
58, 7, 7
11, 43, 23
8, 55, 38
22, 55, 41
29, 43, 35
Right medial frontal gyrus
Left medial frontal gyrus
Right inferior frontal gyrus
Right dorsal ACC
Right middle temporal gyrus
Left middle temporal gyrus
Right posterior cingulate gyrus
Right precuneus
Left precuneus
Right inferior parietal lobule
BA
BA
BA
BA
BA
BA
BA
BA
BA
BA
None
None
None
9
10
47
32
21
21
23/30
7
7
31
Volume (mm3)
t-value for peak activation
513
702
270
405
1215
405
1188
324
837
405
4.47
3.95
2.89
3.37
3.91
3.85
2.63
3.08
4.45
2.93
None
None
Talairach coordinates and t-values for peak activation in significant clusters (P < 0.025 with contiguity threshold; minimum volume threshold ¼ 270 mm3) representing greater
activation in one group relative to the other for the incidental vs directed condition.
Correlation between behavioral performance and
functional activation for the directed and
incidental conditions
Based on the findings of group differences in neural
activation in the whole-brain analyses, Pearson correlation
analyses (two tailed) were performed for each group to
further examine the relationship between profiles of behavioral performance and functional activation (i.e. volume in
voxels) in functionally relevant ROIs (amygdala,
parahippocampal gyrus, dorsal ACC, subgenual ACC, posterior cingulate gyrus, DLPFC, VLPFC, middle temporal
gyrus, precuneus, inferior parietal lobule and caudate) for
the directed and the incidental condition. Regarding the
incidental condition, adults exhibited a significant positive
correlation between accuracy rates and activation in the right
subgenual ACC (r ¼ 0.73, P ¼ 0.02), whereas adolescents
exhibited only a non-significant trend in this regard
(r ¼ 0.60, P ¼ 0.07). For the directed condition, both
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Adults
Incidental > directed
Directed > incidental
Volume (mm3)
Talairach coordinates for peak values
Facial emotion processing in adolescents
SCAN (2009)
393
Table 4 Adolescents vs adults for each condition vs fixation
Incidental vs fixation
Adolescents > adults
Region
BA
Volume (mm3)
t-value for peak activation
41, 14, 29
2, 65, 5
50, 64, 29
58, 40, 7
29, 79, 13
20, 34, 1
19, 37, 1
22, 6, 12
2, 13, 29
2, 46, 26
7, 55, 11
1, 64, 23
53, 11, 23
Right middle frontal gyrus
Right medial frontal gyrus
Right middle TG
Left middle TG
Right fusiform gyrus
Right parahippocampal gyrus
Left parahippocampal gyrus
Right amygdala*
Right mid-CG
Right posterior CG
Left posterior CG
Left precuneus
Right inferior frontal gyrus
BA 9
BA10
BA 39
BA 21
BA 19
BA 27
BA 30
BA
BA
BA
BA
BA
23
31
30
31
45
783
2781
378
945
621
621
864
135
729
1080
1053
810
621
2.57
3.75
3.15
2.91
4.09
2.68
4.00
2.82
3.85
3.81
3.17
3.47
4.06
32, 79, 13
52, 64, 1
17, 1, 26
6, 5, 44
11, 38, 5
40, 34, 1
Right fusiform gyrus
Left middle TG
Right dorsal ACC
Left dorsal ACC
Right pregenual ACC
Left caudate
BA
BA
BA
BA
BA
19
37
24
24
32
486
810
378
270
297
297
5.12
3.28
3.00
2.45
2.74
2.66
Talairach coordinates and t-values for peak activation in significant clusters (P < 0.025 with contiguity threshold; minimum volume threshold ¼ 270 mm3) representing greater
activation in one group relative to the other for each condition vs fixation. *Significant cluster at P < 0.05.
adolescents (r ¼ 0.83, P ¼ 0.003) and adults (r ¼ –0.66,
P ¼ 0.04) showed a significant correlation between performance (in terms of accuracy for adolescents and RT for
adults) and activation in the right amygdala.
Finally, we carried out Pearson’s linear regression analyses
with age as a predictor, both with regard to behavioral performance (RT and accuracy), and with regard to functional
activation in significant ROIs that revealed group differences
in the whole-brain ANOVA (DLPFC, VLPFC, amygdala and
dorsal ACC). No significant results of age as a predictor were
found for either condition, possibly because of sample
size limitations.
sub-cortical automatic emotion processing during affective
challenge (Blumberg et al., 2004; Marsh et al., 2006; Bell and
Deater-Deckard, 2007; Yurgelun-Todd, 2007). Furthermore,
as often found in developmental fMRI studies (Monk et al.,
2003; Nelson et al., 2003; Passarotti et al., 2007), these
differences in neural activation occurred in the absence of
significant group differences in behavioral performance for
either condition, suggesting that because of brain immaturity, adolescents may need to engage cognitive and affective
neural networks differently than adults in order to reach
performance levels comparable with adult ones (Nelson
et al., 2003).
DISCUSSION
In line with our first hypothesis, the present fMRI findings
showed that for the incidental face emotion processing
condition vs fixation adolescents, compared with adults,
exhibited increased paralimbic activation (i.e. right amygdala
and bilateral parahippocampal gyrus), which was also
coupled with reduced activation in right VLPFC (i.e. right
inferior frontal gyrus, BA 45). Confirming our second
hypothesis, for directed processing of face emotions vs fixation, adolescents, relative to adults, exhibited less activation
in the right dorsal and pregenual ACC (i.e. left dorsal ACC,
BA 24; right pregenual ACC, BA 32), two cingulate regions
interfacing with VLPFC and DLPFC functions (MacDonald
et al., 2000; Petrides and Pandya, 2002), which may indicate
ACC functional immaturity during face emotion processing.
These findings are consistent with the viewpoint that
with development, there is increased prefrontal control of
Incidental vs directed emotion processing
in each group
For the incidental vs the directed condition, adolescents
exhibited greater activation in right DLPFC, a region
involved in cognitive control, attention and working
memory processes (Mesulam, 1999; MacDonald et al.,
2000). This is likely due to a greater attentional effort
(Compton et al., 2003) for the age judgment than for
the face emotion decision in adolescents. Moreover, they
exhibited greater bilateral paralimbic activation, which was
accompanied by greater right VLPFC and dorsal ACC activation. Furthermore, adolescents showed greater activation
for the directed than for the incidental condition only in
temporal regions that process facial expressions (Haxby
et al., 2002), and inferior parietal regions that are part of
the visuospatial attention network (Mesulam, 1999).
Therefore, this pattern of results can be interpreted as
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Adults > adolescents
Directed vs fixation
Adolescents > adults
Adults > Adolescents
Talairach coordinates for peak values
394
SCAN (2009)
A. M. Passarotti et al.
Downloaded from http://scan.oxfordjournals.org/ at UIC Library, Collections Development on March 24, 2015
Fig. 2 Significant group differences in activation for whole-brain ANOVA, group by condition interaction: [F(1,18) ¼ 5.04, P < 0.01] (left side), and ROI analyses (right side) for
the incidental condition vs fixation (A–F) and for the directed condition vs fixation (G and H). In the whole-brain effect size maps, red clusters of activation indicate significantly
(P < 0.025, corrected) greater activation in adolescents compared with adults, and blue clusters indicate significantly (P < 0.025, corrected) reduced activation in adolescents
compared with adults. (A) For the incidental condition vs fixation, the adolescent group had significantly greater activation than the adult group in right DLPFC (TLRC coordinates
for peak activation: 41, 14 and 29). (B) Bar graph of activation during the incidental and directed conditions relative to fixation for the right DLPFC ROI shows greater right DLPFC
activation in adolescents compared with adults for the incidental condition, in the significant group by condition interaction [F(1,18) ¼ 6.25, P < 0.02]. (C) For the incidental
condition vs fixation, the adolescent group exhibited significantly reduced activation than the adult group in right VLPFC (TLRC coordinates for peak activation: 53, 11 and 23).
(D) Bar graph of activation during the incidental and directed conditions relative to fixation for the right VLPFC ROI shows reduced right VLPFC activation in adolescents compared
with adults for the incidental condition, in the significant group by condition interaction [F(1,18) ¼ 4.26, P < 0.05]. (E) For the incidental condition vs fixation, the adolescent
group exhibited significantly greater activation than the adult group in right amygdala (TLRC coordinates for peak activation: 22, –6 and –12) (in this small region, the corrected
P < 0.05). (F) Bar graph of activation during the incidental and directed conditions relative to fixation for the right amygdala ROI shows greater right amygdala activation in
adolescents than adults for the incidental condition in the significant group by condition interaction [F(1,18) ¼ 4.70, P < 0.04]. (G) For the directed condition vs fixation, the
adolescent group exhibited significantly reduced activation, compared with adults, in right dorsal ACC (TLRC coordinates for peak activation: 17, –1 and 26). (H) Bar graph of
activation during the incidental and directed conditions relative to fixation for the right dorsal ACC ROI shows reduced right dorsal ACC activation in adolescents than adults in
the directed condition in the significant group by condition interaction [F(1,18) ¼ 4.16, P < 0.05]. Error bars in bar graphs represent SE values. Note that the right side of the
brain image corresponds to the left hemisphere and the left side corresponds to the right hemisphere.
Facial emotion processing in adolescents
Incidental vs directed emotion processing
between groups
When directly comparing the two groups for the incidental
vs directed condition, it emerged that the adolescent group
showed greater activation than the adult group in right
DLPFC, cingulate cortex (dorsal ACC and posterior cingulate gyrus) and parietal regions, most likely because of
greater attentional effort during the age judgment condition
in the younger group (MacDonald et al., 2000). Adolescents
also engaged the right VLPFC more than adults for the
incidental relative to the directed condition, possibly because
of a greater need to regulate excessive automatic emotion
processing (Adolphs, 2002; Petrides and Pandya, 2002;
Pavuluri et al., 2007).
Animal (Goldman-Rakic, 1987) and human (Posner and
Petersen, 1990) neurophysiological studies have identified
the ACC as a part of both distributed attentional and
emotion processing networks (Vogt et al., 1992; Devinsky
et al., 1995; Bush et al., 2000). The dorsal ACC has connections to the PFC and parietal cortex and plays an important
role in conflict monitoring (Bush et al., 2000; Botvinick
et al., 1999) and cognitive regulation (Posner and
Rothbart, 2000; Marsh et al., 2006). The ACC undergoes
protracted anatomical (Casey et al., 1997; Cunningham
et al., 2002) and functional (Adelman et al., 2002; Nelson
et al., 2003; Velanova et al., 2008) maturation from infancy
to adolescence. Our findings of developmental differences in
395
ACC involvement for the incidental vs directed condition
are similar to previous findings of differential ACC involvement in adolescents relative to adults during incidental
encoding (Monk et al., 2003; Nelson et al., 2003) and passive
viewing of emotional faces (Monk et al., 2003). The developmental differences in ACC engagement for the incidental
vs the directed condition may be related to the fact that
emotional stimuli draw attention to a greater degree in
the younger age group, because there is greater emotional
modulation of cognitive processing in children compared
with adults (Nelson et al., 2003, 2005). Similarly, Deeley
et al. (2008) found decreased dorsomedial and middle frontal cortex activation with age in response to emotional faces
in healthy males, which was attributed to a possible
reduction in attentional demands, or in processing the selfrelevance of facial expressions during social interactions in
adulthood.
Incidental face emotion processing in adolescents
compared with adults
When comparing the two groups for the incidental
condition relative to fixation, adolescents exhibited greater
activation than adults in bilateral parahippocampal regions,
right amygdala (though with a less stringent probability
threshold) and right fusiform gyrus, and reduced activation
in right VLPFC. Increased amygdala reactivity in adolescents
compared with adults was found during incidental processing of face affect (Monk et al., 2003; Guyer et al., 2008) and
during an emotional go-nogo task with emotional faces
(Hare et al., 2008). Moreover, the VLPFC is a region that
comes to play a primary role in self-regulatory control
(Marsh et al., 2006) and emotion regulation (Pavuluri
et al., 2009) with development. It, therefore, seems that in
adolescents, relative to adults, there is greater automatic
sub-cortical reactivity to emotional content, even when
emotion processing is not necessary, which is accompanied
by poor VLPFC control of the emotional circuits. These
findings provide some support to the hypothesis that with
normal development, there is increased cortical cognitive
control over automatic sub-cortical emotional reactivity,
possibly resulting in better executive functions and
emotional regulation (Adolphs, 2002; Marsh et al., 2006).
It is interesting that recent developmental fMRI studies
with adolescents suffering from affect disorders indicate a
greater exacerbation of sub-cortical reactivity and reduced
prefrontal regulation, and/or a delay in the normal developmental trajectory of cortical regulation of affect in these
individuals. In fact, Pavuluri et al. (2009) found similar
results of greater amygdala reactivity and reduced VLPFC
control for incidental processing of face emotions in adolescents with bipolar disorder compared with healthy adolescents in the same age range as our participants. Furthermore,
Hare et al. (2008) found that during an emotional go-nogo
task with affective faces, individuals with higher trait anxiety,
relative to healthy peers, did not exhibit habituation in
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suggesting that brain activation in adolescents is relatively
more modulated by the emotional content of stimuli than by
task instructions, and that during the incidental condition
they automatically process face affect, even when it is not
task-related (see also Monk et al., 2003). Moreover, they
engage ventral and medial PFC regions most likely in an
attempt to regulate and evaluate automatic emotional
reactivity in sub-cortical circuits.
In agreement with previous findings with adults (Hariri
et al., 2000; Gorno-Tempini et al., 2001) in the present study,
adults showed greater activation for the directed than the
incidental condition in ventral and medial prefrontal regions
that typically process, evaluate and regulate emotional content (i.e. VLPFC, medial PFC and pregenual ACC) (Adolphs,
2002; Petrides and Pandya, 2002; Pavuluri et al., 2007).
Similar to adolescents, adults showed greater activation in
DLPFC for the incidental than the directed condition, likely
due to greater attentional effort for the age judgment than
the face emotion judgment (MacDonald et al., 2000;
Compton et al., 2003). Therefore, confirming our third
hypothesis, our data suggest that in adults, as expected, it
is the directed face emotion processing condition, which
requires explicit face emotion processing, that elicits greater
cortical regulation of emotion processing as compared with
the incidental condition, for which emotion processing is
not necessary (Hariri et al., 2000; Gorno-Tempini et al.,
2001; Monk et al., 2003).
SCAN (2009)
396
SCAN (2009)
Directed face emotion processing in adolescents
compared with adults
For the directed condition, adolescents exhibited greater
activation than adults in right fusiform gyrus and less activation than adults in ACC regions (i.e. right pregenual ACC
and bilateral dorsal ACC). The two groups did not differ
significantly for amygdala activation during the directed
condition. The dorsal ACC is important for cognitive
conflict modulation (Bush et al., 2000; Botvinick et al.,
1999), whereas the subgenual and pregenual ACC, together
with the VLPFC, exert control over amygdala emotional
reactivity (Bush et al., 2000; Botvinick et al., 1999).
Increases in ACC volume (Casey et al., 1997) and functional
activation (Velanova et al., 2008) from childhood to late
adolescence have been associated with better control of
cognitive conflict and error monitoring. The present findings
of reduced dorsal and pregenual ACC activation in adolescents compared with adults during the condition explicitly
requiring face emotion processing suggest that even in late
adolescence, the cognitive and emotion modulation functions of the dorsal and pregenual ACC, respectively, are
still developing. Therefore, adolescents, compared with
adults, seem less able to engage in cognitive regulation of
directed face emotion processing. Our findings agree with
those of Williams et al. (2006) who found greater selective
control of medial prefrontal systems over emotion functions
in adults compared with adolescents.
Lastly, both for the directed and the incidental conditions
we found greater right fusiform activation in adolescents
compared with adults. Greater fusiform gyrus activation in
children and adolescents compared with adults has been
found for face processing in previous developmental
fMRI studies and has been attributed to immature specialization of regional brain function (Passarotti et al, 2003, 2007;
Gathers et al., 2004; Aylward et al., 2005). Alternatively,
it may be attributed to increased attentional modulation of
fusiform activity by means of emotional stimuli in adolescents than in adults (Veuilleumier et al., 2001; Nelson et al.,
2005).
Developmental differences in the neural correlates
of behavioral performance for the incidental and
directed condition
With regard to the directed condition, for both groups a
significant positive correlation of performance measures
and functional activation was found only for the right amygdala. Therefore, the right amygdala, which is crucial
for processing of facial emotions (Adolphs, 2002), seems to
be the closest neural correlate of directed face emotion
processing performance in this study. This finding is in
line with evidence of early functional specialization of the
amygdala (Johnson, 2005) and with our whole-brain
analyses, which did not reveal age differences in amygdala
activation for the directed condition. On the contrary, our
results suggest that the neural correlates of performance for
the incidental condition may present a slower developmental
timetable. In fact, adults showed a positive correlation
between accuracy rates and activation in the subgenual
portion of the right ACC, an important region that helps
the VLPFC to regulate affect processes (Whalen et al., 1998;
Bush et al., 2000; Kemmotzu et al., 2005; Pavuluri et al.,
2007); however, adolescents showed only as a non-significant
trend for this regions, which may be indicative of greater
individual variability associated with ongoing functional
development (Conel, 1967; Adelman et al., 2002).
Finally, the present study has limitations in sample size
and represented age ranges that call for future investigations
with larger samples of children and adolescents across the
age span. Moreover, since we adopted a block design, for
which each block contained both positive and negative facial
emotion trials, we were not able to contrast group differences in activation for positive vs negative facial emotions,
and we also could not differentiate between neural activation
for correct and incorrect responses. Therefore, future
event-related fMRI studies will be useful in differentiating
neural mechanisms that underscore processing of negative vs
positive emotional content as well as correct relative to
incorrect responses for directed vs incidental processing of
emotions.
CONCLUSIONS
The present fMRI findings provide initial evidence that
progressive cortical control over sub-cortical emotional
circuits may represent the normal developmental trajectory
of emotion regulation systems, and that this process continues through adolescence. Future investigations with
larger samples and greater age ranges will help define the
normative developmental timetable of maturation in the
neural bases of emotional self-regulation. These investigations could also potentially inform clinical models on the
possible neural deviations from the normal developmental
trajectory of emotion regulation circuitries that may lead to
affect dysregulation in developmental populations
(Blumberg et al., 2004; Nelson et al., 2005; Bell and
Deater-Deckard, 2007; Pavuluri and Passarotti, 2008).
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amygdala reactivity over repeated stimulus exposure, and
this was also associated with reduced functional connectivity
between VLPFC and amygdala. Finally, it is of interest that
adolescents with anxiety disorder, compared with healthy
controls, were found to exhibit amygdalar hyper activation
(McClure et al., 2007; Beesdo et al., 2009) and increased
VLPFC and ACC activity (McClure et al., 2007) in response
to fearful faces when focusing their attention on internally
experienced fear (i.e. during subjective-state monitoring of
fear). These findings point to the importance of further
studying how emotional circuits may abnormally shape
the cognitive-attentional systems during development in
children and adolescents with mood disorders (Nelson
et al., 2005).
A. M. Passarotti et al.
Facial emotion processing in adolescents
Conflict of Interest
Dr A.M.P. has no financial relationships to disclose.
Dr J.A.S., unrelated to this work, has received support
from NIMH, GlaxoSmithKline, AstraZeneca, Janssen and
Eli Lilly. Dr M.N.P’s work, also unrelated to this manuscript,
is supported by NARSAD Independent Investigator Award,
NICHD, NIMH, Dana Foundation, American Foundation
for Suicide Prevention, GlaxoSmithKline-NeuroHealth
(Investigator-initiated study), Astra Zeneca (Speaker),
Abbott Pharmaceuticals (Study Drug) and Janssen
Research Foundation (Study Drug).
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