Cerebral Cortex, 2019;00: 1–16

doi: 10.1093/cercor/bhz266
Advance Access Publication Date:
Original Article

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ORIGINAL ARTICLE

Emotional Interference in Early Adolescence: Positive

Reinforcement Modulates the Behavioral and Neural
Effects of Negative Emotional Distracters
Neil P. Jones1 , Michael Schlund1,2 , Rebecca Kerestes1 and Cecile D.
Ladouceur1
1 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA and
2 Department of Psychology, Georgia State University, Atlanta, GA 30302, USA
Address correspondence to Neil P. Jones, Department of Psychiatry, University of Pittsburgh, 3811 O’Hara Street, Pittsburgh, PA 15213, USA.
Email: jonesnp@upmc.edu

Abstract
Limited research has examined functioning within fronto-limbic systems subserving the resistance to emotional
interference in adolescence despite evidence indicating that alterations in these systems are implicated in the
developmental trajectories of affective disorders. This study examined the functioning of fronto-limbic systems subserving
emotional interference in early adolescence and whether positive reinforcement could modulate these systems to promote
resistance to emotional distraction. Fifty healthy early adolescents (10–13 years old) completed an emotional delayed
working memory (WM) paradigm in which no distractors (fixation crosshair) and emotional distracters (neutral and
negative images) were presented with and without positive reinforcement for correct responses. WM accuracy decreased
with negative distracters relative to neutral distracters and no distracters, and activation increased in amygdala and
prefrontal cortical (PFC) regions (ventrolateral, dorsomedial, ventromedial, and subgenual anterior cingulate) with negative
distracters compared with those with no distracters. Reinforcement improved performance and reduced activation in the
amygdala, dorsomedial PFC, and ventrolateral PFC. Decreases in amygdala activation to negative distracters due to
reinforcement mediated observed decreases in reaction times. These findings demonstrate that healthy adolescents recruit
similar fronto-limbic systems subserving emotional interference as adults and that positive reinforcement can modulate
fronto-limbic systems to promote resistance to emotional distraction.

Key words: adolescence, cognitive control, emotion, motivation, working memory

Introduction adolescence (cf., Vetter et al. 2015; Ladouceur et al. 2018). As

The ability to sustain attention on goal-directed behavior while
resisting interference from distracting emotional information
(e.g., focusing on one’s teacher and ignoring an angry class-
mate) is critical for adaptive behavior. In adults, the ability
to successfully prevent emotional interference appears to rely
on complex interactions between frontal and limbic systems
(e.g., Dolcos et al. 2006; Dolcos and McCarthy 2006). However,
limited research has examined functioning within fronto-limbic
systems subserving the resistance to emotional interference in
such, it is unclear whether findings from the adult literature
extend to adolescents. Replication with adolescents could have
important clinical implications in light of evidence suggesting
that the altered functioning of fronto-limbic systems may con-
tribute to the developmental trajectories of risk for affective
disorders (Joormann et al. 2007; Ladouceur et al. 2009, 2013;
Ladouceur 2012). Furthermore, given that emotional interfer-
ence is a disruptive characteristic of affective disorders in adults
(Jones et al. 2015, 2016) and adolescents (Colich et al. 2017),

© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
 2 Cerebral Cortex, 2019, Vol. 00, No. 00
identifying variables or procedures that can be used to buffer
against interference-related declines in goal-directed behavior
is an important yet largely unexplored area of research (cf.,
Ladouceur et al. 2018).
According to some theories, emotional information is prior-
itized over concurrent goal-directed activity (Mogg et al. 2000;
Armony and Dolan 2002), because emotion information contains
signals closely linked to survival (LeDoux 2000). Thus, emo-
tion information is highly motivationally salient and captures
attention (Anderson and Phelps 2001; Piech et al. 2011). Some
models posit that emotional information can cause interference
with ongoing goal-directed activity because it competes for
resources at both perceptual and executive levels of processing
(i.e., the dual competition model; Pessoa 2009). This competition
for limited resources arises because emotional information is
integrated with cognitive control processes through complex
interactions between subcortical and prefrontal regions (Pessoa
2015). Using cognitive tasks modified to include task irrele-
vant emotional distracters, numerous studies have provided
evidence that emotional stimuli tend to “hijack” attention more
easily than nonemotional stimuli resulting in disrupted goal
pursuit and less optimal task performance (e.g., slower reaction
times and reduced accuracy; Dolcos and McCarthy 2006; Antice-
vic et al. 2010; Denkova et al. 2010). The magnitude of the inter-
ference effect varies as a function of how arousing the emotional
information is and its task relevance such that highly arous-
ing, task-irrelevant emotional information results in a greater
diversion of executive resources and stronger negative impact
on performance, particularly in the context of mental illness
(Schweizer et al. 2019).
One task that has been used to examine the functioning of
fronto-limbic systems underlying attentional control in the con-
text of emotional distracters is the emotional delayed working
memory (EDWM) task. The EDWM task is a modified version of
a visual delayed match-to-sample task that includes a visual
probe held in working memory (WM) during a delay period and
typically involves the presentation of no distracter, a neutral dis-
tracter, or an emotional distracter (e.g., negatively valenced pic-
tures). In adults, recent meta-analyses of emotional interference
(Hung et al. 2018; Schweizer et al. 2019) have found that process-
ing negative emotional distracting information is consistently
associated with increased activation in the temporo-occipital
lobe, including the fusiform gyrus (i.e., the ventral visual stream),
the ventrolateral prefrontal cortex (VLPFC), orbital frontal cor-
tex (OFC), and the amygdala, and decreased activation in the
dorsolateral prefrontal cortex (DLPFC). This pattern of activa-
tion is typically interpreted as an indication that the resources
allocated to the DLPFC—implicated in active maintenance of
task-relevant information—is momentarily commandeered due
to the salience and biological relevance of the visual affective
stimuli, as processed by the amygdala and OFC (Dolcos et al.
2008). Consistent with this assertion, studies demonstrate that
greater activation within the amygdala (Anticevic et al. 2010;
Dolcos et al. 2013) and decreased activation in the DLPFC during
the delay period (Dolcos and McCarthy 2006; Dolcos et al. 2008)
are associated with poorer WM accuracy. Furthermore, evidence
consistently points to activation with the VLPFC serving a key
role in coping with emotional interference. Increased VLPFC
activation is associated with decreased subjective ratings of
distractibility and the emotionality of negative affective stimuli
(Dolcos and McCarthy 2006), as well as increased WM accuracy
(Dolcos et al. 2006, 2013; Dolcos and McCarthy 2006; Anticevic
et al. 2010; Iordan and Dolcos 2017).
The majority of research into the functioning of fronto-limbic
systems subserving resisting emotional interference has been
conducted in adults. Investigating the functioning of these sys-
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tems with different age groups is an important step needed to
firmly establish the generality of emotional interference effects
and presumed brain mechanisms. Given evidence that pre-
frontal cortical (PFC) regions and their connectivity to subcor-
tical regions, such as the amygdala, undergo important mat-
urational changes during adolescence (Gee et al. 2013; Casey
et al. 2019), while subcortical regions implicated in emotional
processing are particularly active compared with younger chil-
dren and adults (Guyer et al. 2016), it is possible that ado-
lescents could show greater emotional interference associated
with less activation in PFC regions than adults. Limited evi-
dence is emerging which supports the generality of emotional
interference effects and the presumed brain mechanism in ado-
lescents. Vetter et al. (2015) used a perceptual discrimination
task to examine emotional interference. Preventing emotional
interference was operationalized as the ability to correctly com-
pare two shredded images to determine their equality while
ignoring emotional stimuli. Preventing emotional interference
was contrasted against attending to emotional stimuli, oper-
ationalized as determining the equality of intact emotional
stimuli while ignoring shredded emotional stimuli. Attending
to emotional stimuli relative to resisting emotional interference
was associated with increased activation in the ventral visual
stream, amygdala (to negative stimuli only), and VLPFC, and with
reduced activation in the DLPFC and inferior parietal lobe. Simi-
larly, in our preliminary study conducted in a separate small and
under-powered sample, we have demonstrated that processing
emotional distracters is associated with greater activation in the
amygdala, ventromedial prefrontal cortex (vmPFC) extending
into the dorsomedial prefrontal cortex (dmPFC), and the VLPFC
during the delay period of the EDWM task adapted for use
with adolescents (Ladouceur et al. 2018). Taken together, these
studies begin to demonstrate that the same pattern of fronto-
limbic interactions observed in the adult literature is replicat-
ing in adolescence. While illustrative, neither study examined
brain-behavior associations. Specifically, no identified research
in adolescence has examined associations between amygdala
functioning and WM performance despite evidence from the
adult literature indicating such an association exists (Anticevic
et al. 2010; Dolcos et al. 2013). Thus, the first goal of the current
investigation is to replicate and extend findings in young ado-
lescents by examining the functioning of fronto-limbic systems
underlying resistance to emotional interference and examining
brain-behavior associations to elucidate potential brain mecha-
nisms underlying resistance to emotional interference.
Given that susceptibility to emotional interference is a
deficit present in both adults (Jones et al. 2015, 2016) and
adolescence (Colich et al. 2017) diagnosed with affective
disorders, identifying variables or procedures that can be
used to prevent interference and associated declines in goal-
directed behavior are an important yet largely unexplored
area of research. In particular, research indicates that affective
disorders are associated with biased processing of emotional
stimuli (Ladouceur et al. 2005; Monk et al. 2008; Phillips et al.
2008; Britton et al. 2013) and abnormal recruitment of top-down
cognitive control, particularly in the presence of interfering
emotional stimuli (e.g., fearful images, Colich et al. 2017) and
internal emotional states (e.g., anxious arousal, Jones et al.
2015, 2016), which are associated with deficits in goal-directed
behavior. Hence, there is a need to identify ways of promoting

attentional control of emotion. As reviewed, evidence suggests
that emotional responses and emotional interference can be
mitigated by increased recruitment of top-down cognitive
control regions (Dolcos et al. 2006, 2013; Dolcos and McCarthy
2006; Anticevic et al. 2010). A number of animal and human
neuroimaging studies have shown that positive reinforcement
(i.e., receipt of a reward following a specific response) boosts
behavioral performance on cognitive control tasks such as
WM (Watanabe 1996; Pochon et al. 2002; Beck et al. 2010;
Jimura et al. 2010; Bahlmann et al. 2015; Iordan and Dolcos
2017; Bruening et al. 2018) and that such improvement in
performance is associated with increased neural activation
in dorsal and lateral PFC regions. Such findings suggest that
positive reinforcement for correct responding on the EDWM
task could boost behavioral performance by counteracting
the effects of emotional interference. There are a number of
potential routes through which positive reinforcement may
exert influence. These include reduced activation in brain
regions supporting the processing and coping with emotional
distracters (e.g., amygdala, vmPFC and VLPFC), which was
observed in our preliminary study (Ladouceur et al. 2018),
increased activation in attentional control regions (lateral
prefrontal cortex), or both. As such, it is likely that reduced
activation in emotional processing regions and/or increased
activation in prefrontal cognitive regions occurring as a function
of reward could mediate changes in behavior performance.
Accordingly, the second goal of this study was to test the
extent to which providing positive reinforcement (i.e., monetary
rewards for correct responses) would improve task performance
and modulate activation in PFC and subcortical regions involved
in emotional interference in a larger sample of adolescents.
We hypothesized that: 1) we would replicate in adolescents
the patterns of activation associated with emotional interfer-
ence observed in adults; 2) positive reinforcement would be
associated with reduced activation in limbic and ventral neural
regions (i.e., amygdala and VLPFC); 3) greater amygdala activa-
tion during negative emotional distracters would be associated
with poorer accuracy and slower reaction times; and 4) the
magnitude of the decrease in amygdala activation, in response
to emotional distracters, due to positive reinforcement would
mediate changes in task performance.
Materials and Methods
Participants
One hundred and one healthy youths (52% girls) aged between
10 and 13 years old and with no history of psychiatric or neu-
rological disorders participated in the study. Participants were
recruited from the community through advertisements and fly-
ers. They were recruited to be within a narrow age-range due to
the aims of the larger longitudinal project in which participants
were enrolled. Thirty-eight participants were excluded for hav-
ing excessive motion (i.e., >25% of scans with motion >5 mm
and/or 3 standard deviation [SD] intensity shifts) as determined
by ArtRepair (Mazaika et al. 2005); 13 were excluded for poor
behavioral performance (<65% accuracy). Analyses were con-
ducted on the remaining 50 participants (mean age: 12.00 years;
SD = 1.06, range: 10.11–13.91 years, 58% female, 72% Caucasian,
18% African American, and 5% unknown).
Exclusion criteria included the presence of psychiatric
disorder, visual disturbance (<20/40 Snellen visual acuity),
being pregnant, MRI contraindications (e.g., metal in the body,
Emotional Interference in Adolescence Jones etal. 3
claustrophobia), or taking oral steroids. Parental informed
consent was provided and adolescent assent was obtained
prior to scanning. The study was approved by the University
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of Pittsburgh Institutional Review Board. Participants received
performance-based earnings in addition to compensation for
their participation.
Screening Measures
The Columbia Diagnostic Interview for Children (Shaffer et al.
2000) a computerized structured interview used with adoles-
cents and their parent about their child, was used to screen
participants for the presence of psychiatric diagnosis based
on criteria from the DSM-IV (American Psychiatric Association
1994).
Pretask Practice
Immediately prior to the scanning session, participants read
instructions and completed a shortened version of the task
in a mock scanner to familiarize them with the EDWM task.
The practice session also included training participants to map
numbers 1–2 to corresponding buttons on the response glove as
well as exposing participants to the sounds of the scanner and
teaching them how to remain still during the scan.
fMRI EDWM Paradigm
Participants completed two fMRI paradigms during a 90-min
MRI scan at the Magnetic Resonance Research Center, University
of Pittsburgh Medical Center Health System, USA. The focus of
the current investigation was their performance on an adapted
version of the EDWM task (Anticevic et al. 2011). The EDWM
task included 80 trials of a version of a delayed match-to-
sample task (Sternberg 1969) with two geometric shapes and
two potential distracter types presented during the delay or the
maintenance period of the task: emotionally negative images
and visually complex neutral images (see Fig. 1). Trials began
with the presentation of the memoranda (3 s) followed by a
fixation cross (1 s), a delay period (fixation cross (10 s) or dis-
tracter (3 s) and fixation cross (7 s)), the probe (2.5 s), inter-
trial stimulus (in blocks without positive reinforcement: fixation
cross (7 s); in blocks with positive reinforcement, feedback (0.5 s):
“Correct: win $1” written in green following correct responses or
“Wrong: no money” written in red following incorrect responses
or “No response” written in white following omissions and fix-
ation cross (6.5 s). A PC running E-prime software (psychology
software tools (PST)) controlled stimulus display. A color high-
resolution LCD projector projected visual stimuli onto a rear
screen at the head of the scanner bore, viewable via a mirror
attached to the head coil. Responses were recorded using a PST
glove.
The 80 trials of the EDWM task were divided according to
distracter type: 30 negative distracter trials, 30 neutral distracter
trials, and 20 no distracter trials, which were blank trials with
a fixation cross used to estimate distracter-free maintenance
activity. The trials were grouped into eight blocks of 10 trials
each. The first two blocks included trials with no distracters
(block 1 without positive reinforcement and block 2 with posi-
tive reinforcement). The following six blocks included 30 neu-
tral and 30 negative trials presented in a fixed random order
within each block. Three blocks were presented without positive
reinforcement (blocks 3, 5, and 7), and three blocks included
 4 Cerebral Cortex, 2019, Vol. 00, No. 00
Figure 1. Illustration of the adapted version of the EDWM task with and without positive reinforcement for correct responding on trials with no, neutral or negative
distracters. ITI: interstimulus interval.
positive reinforcement (blocks 4, 6, and 8). The even-numbered
blocks included the same trials and timing as the odd-number
blocks but with the added instructions and feedback pertain-
ing to reinforcement. Each trial lasted 24 s with each block
lasting 4.3 min. As in Anticevic et al. (2010), the memory sets
were constructed from complex geometric shapes (Attneave
and Arnoult 1956) created using a MATLAB algorithm designed
to generate geometric shapes that were not easily described
and encoded verbally (Collin and McMullen 2002). The negative
and neutral distracters were a subset of digitized slides from
the international affective picture system (IAPS) stimulus set
(Lang et al. 2008) selected for use with children and adolescents
(McManis et al. 2001). All distracters were presented at the center
of the screen, with a visual angle of 8.5◦ . At the end of the scan,
participants were informed that the monetary reward received
was to be added to their participant payment card.
Prior to the start of the experiment, each participant was
presented with instructions explaining the task and completed
a practice session. They were instructed to try to remember
two shapes presented on the screen and to keep their eyes
looking at the center of the screen and to not respond once
the shapes disappeared. They were also told that a single shape
would then be presented for a brief time and to press a button
with their index finger (yes) if this shape matched one of the
shapes previously presented and to press a button with their
middle finger (no) if this shape did not match any of the shapes.
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They were also informed that at some point during the task,
graphic images would be presented. In order to examine the
influence of positive reinforcement on the performance of the
EDWM task, each block was repeated, but the distracters (neutral
and negative) within the blocks were randomized, and blocks
2, 4, 6, and 8 included instructions at the beginning of the
block indicating to the participants that they would receive a
monetary reward ($1) for each correct response.
Manipulation Check: Postscan Valence and Arousal
Rating Task
In order to account for the possibility that the emotional dis-
tracters were not perceived as emotionally salient, participants
performed a computerized valence and arousal rating task
immediately following exiting the scanner. The task consisted of
viewing a series of 80 IAPS pictures (38 negative and 42 neutral)
that were presented in a random order and included pictures
used as emotional distracters in the EDWM task (36%) and
pictures that were randomly selected from the IAPS series (64%).
Participants were asked to use the Self-Assessment Manikin
(Bradley and Lang 1994; Lang et al. 1999) rating scale which is a
nonverbal pictorial assessment technique, to rate their affective
reactions to the pictures in terms of valence (1 = positive to
9 = negative) and arousal (1 = excited and 9 = calm). Only ratings
of images used in the EDWM task were analyzed.

MRI Data Acquisition
Scanning was performed on a 3 T Siemens Biograph mMR scan-
ner. Functional T2∗ weighted images were acquired using an
echo-planar imaging sequence (repetition time (TR): 2000 ms;
echo time (TE): 26 ms; flip angle: 90◦ ; FOV: 205 × 205 mm; acquisi-
tion matrix: 64 × 64; slice thickness: 3.1 mm; number of slices: 38
slices). Field map images were also acquired during the scanning
session (TR: 40 ms; TE: 4.92 ms; TE2: 7.38 ms; flip angle: 35◦ ; field
of view (FOV): 256 × 256 mm; acquisition matrix: 128 × 128; slice
thickness: 3.1 mm; number of slices: 38). Both the functional
T2∗ weighted and field mapping images were acquired as axial
slices aligned with the anterior commissure–posterior commis-
sure (AC–PC) line at midline. Due to a change in parameters
used for the field map acquisition that occurred after study
recruitment had commenced, field maps were not collected for
12 participants. A high-resolution, T1-weighted magnetization-
prepared rapid-acquisition gradient echo anatomical scan was
acquired in the axial plane for each participant at the beginning
of the functional scanning session (slice thickness-1 mm, voxel
size = 1 × 1 × 1 mm3 , 160 slices, TR = 2300 ms, TE = 2.47 ms, flip
angle = 9o , matrix = 256 × 256, FOV = 256 mm).
Data Analyses
Behavioral Data
Accuracy (% hits + % correct rejections/2) and reaction times
(correct trials only) were computed for each condition for each
participant. Data were analyzed using a repeated measures
analysis of variance in SAS V.9.4 with emotional distracter type
(no distracter, neutral or negative) and reinforcement condition
(with or without) as within-subject factors and an alpha crite-
rion set at P < 0.05. Post hoc comparisons were performed using
false discovery rate (FDR) corrections (Benjamini and Hochberg
1995).
fMRI Data
Image preprocessing was performed with Statistical Paramet-
ric Mapping software (SPM8; Wellcome Trust Centre for Neu-
roimaging). These steps included correction for differences in
acquisition time between slices, correction for motion (realign-
ment using six-parameter rigid body), and unwarping using a
field map, coregistration of the unwarped image to the partic-
ipant’s structural image. For the 12 participants’ missing filed
maps, the unwarping preprocessing step was not conducted; the
realigned, motion corrected images were coregistered to the par-
ticipant’s structural image. Images were normalized using the
“unified segmentation” approach, including the segmentation
of the structural image and registration into MNI space (ICBM
template), and then the registration of functional images to MNI
space was performed based on the parameters of the structural
registration. Finally, normalized images were smoothed using a
6-mm FWHM Gaussian kernel.
For the first-level analysis, individual effects were estimated
using the general linear model (GLM) approach implemented
in SPM8. We used a finite impulse response (FIR) approach
to analyze task-related blood oxygen-level-dependent (BOLD)
responses. This allows the statistical model to determine the
shape of the hemodynamic response function across each 24 s
trial. The FIR model was specified with a 2 s sampling rate
resulting in an HRF amplitude being estimated for each TR (i.e.,
12 timepoints). We modeled the onsets of each distracter type
with and without positive reinforcement (i.e., six conditions).
Emotional Interference in Adolescence Jones etal. 5
Only trials with correct responses were used in analyses (With-
out reinforcement: no distracter Mdn = 9, range: 4–10; neutral
Mdn = 12, range: 7–15; negative Mdn = 11, range: 6–14. With rein-
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forcement: no distracter Mdn = 9, range: 6–10; neutral Mdn = 13,
range: 9–15; negative Mdn = 12, range: 8–15). An FIR approach was
used because multiple psychological processes are unfolding in
succession and the main process of interest, that is, emotional
interference, is hypothesized to have a sustained effect whereby
emotional processing continues into another cognitive phase of
the task. Furthermore, modeling only the delay period would
have made it difficult to interpret relative “deactivations” in the
BOLD response.
Second-level voxel-wise analyses testing Hypothesis 1 and
Hypothesis 2, described below, were restricted to regions-of-
interest based on the reviewed literature. An anatomically based
region-of-interest region of interest (ROI) mask of the prefrontal
cortex was created with the automated anatomic labeling atlas
(Tzourio-Mazoyer et al. 2002) of the WFU Pickatlas toolbox (Mald-
jian et al. 2003). A single mask encompassing the ventromedial
(BA 10 and 11), ventrolateral (BA 45 and 47) and the dorsolateral
(BA 9 and 46), regions of the prefrontal cortex was created.
Broadman areas were dilated prior to inclusion in the mask.
Due to our a priori interest in using the amygdala in subse-
quent mediation analyses and to prevent concerns related to
“double dipping,” we extracted averaged activation across all
voxels located within an anatomically defined amygdala ROI, for
each combination of distracter type and reinforcement condi-
tion for each TR (12), for each hemisphere, and for each subject.
The amygdala was anatomically defined using an anatomical
mask created using the WFU Pickatlas toolbox (Maldjian et al.
2003). Amygdala activation was winsorized prior to conducting
brain behavior associations. To our knowledge, there are no
established models proposing dynamic shifts in left and right
amygdala functions across development. Nevertheless, several
meta-analytic reviews of emotional information processing in
adults indicate that the left amygdala is more frequently acti-
vated than the right amygdala, to negative stimuli (Wager et al.
2003; Baas et al. 2004; Fusar-Poli et al. 2009). Thus, given evi-
dence that the amygdala and its connectivity to PFC regions are
still developing during childhood and adolescence (Gee et al.
2013; Casey et al. 2019), it is possible that neurodevelopmental
changes during adolescence may result in differential program-
ming, which we wanted to capture by testing left and right
amygdala independently.
In supplementary analyses, we also conducted whole-brain
analyses that were not restricted these masks (see Supplemen-
tal Tables S1 and S2).
Hypothesis Analysis Strategy
Hypothesis 1
To address our first hypothesis pertaining to the effects
of emotional distracters on fronto-limbic activation, a full
factorial GLM focusing on distracter type (no distracters, neutral
distracters and negative distracters—without reinforcement)
by time (12 TRs) interaction was performed using GLM Flex
Fast2 (http://mrtools.mgh.harvard.edu/index.php?title=GLM_
Flex_Fast2). The Type I error rate was controlled using AFNI’s
3dClustSim using the autocorrelation function (-ACF) option
(Cox et al. 2016). Smoothness was estimated from the level 2
residuals, and a voxel-wise threshold of P < 1 × 10−7 was used
for cluster forming to increase the spatial/anatomical specificity
of the resulting clusters in accordance with recommendations
 6 Cerebral Cortex, 2019, Vol. 00, No. 00
made by Woo et al. (2014). These methods also address issues
raised by Eklund et al. (2016). Results indicated that an extent
threshold of 1 voxel corresponded to a cluster-wise family-wise
error rate of P < 0.05. The small extent threshold is a result of
the very stringent cluster forming threshold given that the ROI
mask’s total volume (total volume = 16 068 voxels) well exceeds
the minimum cluster size for 3dClustSim (128 voxels). Averaged
voxel parameter estimates over time were extracted (based on
the significant clusters from the interaction maps) for each
subject for all conditions.
Using SAS software version 9.4, we examined the significant
distracter by time interaction for each of these significant clus-
ters using mixed effects analyses where condition and time were
modeled as repeated factors with residuals modeled as uncon-
ditional for condition and autoregressive (AR[1]) for time. The
only purpose for computing these models was to conduct simple
contrasts using the appropriate degrees of freedom from the
mixed models; we do not report statistics related to the overall
interaction effects because these estimates for the voxel-wise
analyses limited to the prefrontal cortex would be inflated due
to “double dipping.” A priori simple contrasts (negative > neutral
and negative > baseline distracters) of average activation in the
delay period (8–16 s post-trial onset) were conducted on least
square mean estimates. Parallel mixed effects analyses were
conducted for the anatomically defined left and right amygdala
clusters.
Hypothesis 2
To evaluate the effects of positive reinforcement on fronto-
limbic activation during the negative distracter trials, a full
factorial GLM focusing on negative distracters with and without
positive reinforcement by time (12 TRs) interaction was per-
formed using GLM Flex Fast2. The Type I error rate was con-
trolled using the same method as Hypothesis 1. Smoothness was
estimated from the level 2 residuals and a voxel-wise threshold
of P < 0.001 was used for cluster forming (see Supplemental
Methods for the rationale supporting varying cluster-forming
thresholds). Results indicated that an extent threshold of 75
voxels corresponded to a cluster-wise family-wise error rate of
P < 0.05. Averaged voxel parameter estimates over time were
extracted (based on the significant clusters from the interaction
maps) for each subject for all conditions. Using SAS V9.4, we
examined the significant condition × time interaction for each
of these significant clusters using a mixed effects analysis where
condition and time were modeled as repeated factors with resid-
uals modeled as unconditional for condition and autoregres-
sive (AR[1]) for time. A priori simple contrasts (without > with
reinforcement) of average activation in the delay period (8–16 s)
were conducted on least square mean estimates. Parallel mixed
effects analyses were conducted for the anatomically defined
left and right amygdala clusters.
Hypothesis 3
To evaluate associations between amygdala activation during
the delay period and performance (accuracy and reaction times)
during negative distracters, two mixed effects analyses were
conducted in SAS V9.4 with predicting performance from amyg-
dala activation (8–16 s). We allowed for differences in the asso-
ciation to vary as a function of reinforcement condition by
including an amygdala x condition interaction. Residuals were
modeled as unconditional for condition.
Hypothesis 4
Mediational analyses were conducted using the MEMORE macro
for SAS developed by Montoya and Hayes (2017) to determine
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whether changes in amygdala activation during negative dis-
tracter trials due to reinforcement would mediate changes in
task performance. This macro was used to estimate the total,
direct, and indirect effects of X (reinforcement: with reinforce-
ment vs. without reinforcement) on Y (performance: change in
reaction time, change in accuracy) through the mediator M (i.e.,
change in left/right amygdala activation due to reinforcement)
in a path-analytic form using ordinary least squares regression.
This macro implements the method described by Judd et al.
(2001) to test mediation in within-subject designs. Inferences
about the statistical significance of the indirect effect were
based on confidence intervals generated using bootstrapping
approaches (10 000 samples).
To correct for multiple comparisons for tests of Hypothe-
ses 1 and 2, the significance level was corrected using FDR
q < 0.05. FDR correction was calculated using SAS’s multitest
procedure which uses the raw P-values from simple contrasts
to determine the FDR using the linear step-up method of Ben-
jamini and Hochberg (1995). To correct for the four mediations
tests conducted in Hypothesis 4, all tests of indirect effects
were conducted using a 97.6% confidence interval which corre-
sponds to an FDR q < 0.05 (Benjamini and Yekutieli 2001; Narum
2006).
Delay Timing Sensitivity Analyses
Previous studies have varied in the window used to define the
delay period (Dolcos and McCarthy 2006; Anticevic et al. 2010;
Ladouceur et al. 2018). The inconsistency in the timing of the
delay period calls into question, when during the delay period
are emotional interference effects most likely to be observed. In
previous studies examining emotional interference on cognitive
control regions, the DLPFC and lateral frontopolar cortex (LFPC)
demonstrate maximum deactivations between 4.4 s (Anticevic
et al. 2010) and ∼4.5 s (Dolcos and McCarthy 2006) postdistracter
onset based on the graphs of the time-series in both papers.
We conducted sensitivity analyses to determine if differential
distracter impact on prefrontal cognitive control regions are
more apparent early within the delay period (4-s postdistracter
onset = 8-s postmemoranda onset), which should correspond to
the peak window of difference among conditions, relative to
later during the delay period (6–10 s postdistracter onset = 10–
14 s postmemoranda onset). Given evidence that individual
differences in sustained processing of emotional information
in the amygdala exist, particularly among those with affective
disorders (Siegle et al. 2002), we also examined whether changes
in amygdala activation due to reinforcement during the time
frame most indicative of sustained processing of the negative
distracters prior to probe onset (10–14 s postmemoranda onset)
would be a stronger mediator of changes in task performance
than the entire delay and probe period (8–16 s postmemoranda
onset).
Results
Distracter Ratings
Our manipulation check of distracter type indicated that
participants rated negative distracters as more negatively
valenced, t(48) = 14.12, P < 0.001, Cohen’s d = 2.38, and arousing

Figure 2. Bar charts of (A) mean percent accuracy and (B) mean reaction times on
the EDWM task depicting the main effects of distracter type and reinforcement.
Bars with differing letters within an effect are significantly different from one
another. W/R.: with reinforcement; W/O R.: without reinforcement.
t(48) = −9.02, P < 0.001, Cohen’s d = −1.66 than neutral distracters
(valence: M (SD)negative = 7.0 (1.1) vs. M (SD)neutral = 4.6(0.9);
arousal: M (SD)negative = 5.1 (2.2) vs. M (SD)neutral = 8.0 (1.1)).
Task Performance
Accuracy
Figure 2A shows mean percent accuracy for each distracter
type with and without positive reinforcement. Results from
the repeated measures ANOVA indicated significant main
effects of reinforcement, F(1247) = 28.98, P < 0.001, and dis-
tracter F(2247) = 32.94, P < 0.001, which were not qualified by
a reinforcement × distracter interaction F(2245) = 0.01, P = 0.987.
Participants were more accurate on trials with reinforcement,
M (SE) = 83.6 (1.27), relative to those without reinforcement,
M (SE) = 80 (1.27), t = P < 0.001, Cohen’s d = 0.76. Furthermore,
participants were less accurate in the face of negative dis-
tracters, M (SE) = 75.4 (1.38), relative to neutral distracters, M
(SE) = 81.2 (1.38), t = 4.52, P < 0.001, Cohen’s d = 0.64, and were
more accurate when no distracters were present, M (SE) = 85.8
(1.38), relative to neutral distracters, t = 3.58, P < 0.001, Cohen’s
d = 0.51, and negative distracters, t = 8.10, P < 0.001, Cohen’s
d = 1.14.
Emotional Interference in Adolescence Jones etal. 7
Reaction Time
Figure 2B shows mean reaction times for each distracter
type with and without positive reinforcement. Results from
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the repeated measures ANOVA indicated a significant main
effect of reinforcement, F(1247) = 52.65, P < 0.001, on reaction
time, and distracter F(2247) = 3.84, P = 0.032. Main effects
were not qualified by a reinforcement × distracter interaction
F(2245) = 0.18, P = 0.833. Relative to trials without reinforcement,
M (SE) = 1456 (28.2), trials with reinforcement, M (SE) = 1330 (28.2),
was associated with faster reaction times, t = 7.26 P < 0.001,
Cohen’s d = 1.03. Furthermore, participants demonstrated longer
reaction times in the face of negative distracters, M (SE) = 1408
(29.5) t = 2.24, P = 0.026, Cohen’s d = 0.32; and neutral distracters
M (SE) = 1410 (29.5) t = 2.33, P = 0.021, Cohen’s d = 0.33, relative to
when no distracters were present M (SE) = 1360(29.5). Equivalent
reaction times were observed for negative distracters and
neutral distracters, t = 0.09, P = 0.927, Cohen’s d = 0.01.
Neuroimaging
Examination of Brain Regions Responsive to Differences Between No
Distracter, Neutral Distracter, and Negative Distracter Conditions
Without Reinforcement
Table 1 and Supplemental Table S3 list the brain regions
demonstrating significant distracter type (no distracter, neutral
distracter and negative distracter) × time (12 TRs) interaction
from the region-of-interest analysis, and Figure 3 shows their
anatomical locations. Probing the interaction indicated that the
right amygdala, left subgenual anterior cingulate cortex (sgACC)
(BA 25), left vmPFC (BA 10), bilateral dmPFC (BA 9), left VLPFC
(BA 45/47), and right VLPFC (BA 47) were more active during
the delay period in the negative distracter condition relative
to the no distracter condition (see Fig. 3, FDR < 0.05). Across all
regions-of-interest, activation during the delay period, in the
negative distracter condition, did not statistically differ from
activation during the neutral condition when controlling for
multiple comparisons. However, as shown in Supplemental
Table S4, when a less conservative testing approach was taken—
analyzing the time points of the delay period showing the
highest statistical significance for the contrasts of interest
as in Dolcos and McCarthy (2006)—activation in the negative
condition differed from activation in the neutral condition for
the bilateral amygdala, left sgACC, left VMPFC, and bilateral
dmPFC. Other cognitive control regions in the dorsal and
lateral prefrontal cortex did not differ between conditions
during the delay period (FDR q > 0.05). However, sensitivity
analyses indicated that, early during the early delay period
(8-s postmemoranda onset), bilateral DLPFC and bilateral
LFPC were significantly deactivated in the negative distracter
versus no distracter trials. Moreover, activation in right LFPC
showed significant differences between negative and neutral
distracter conditions. During the later delay period (10–14 s
postmemoranda onset) there were no significant distracter
type-related differences (see Supplementary Table S5).
Examination of Brain Regions Responsive to Positive Reinforcement
During the Presentation of Negative Distracters
Table 2 lists the brain regions demonstrating significant rein-
forcement (negative distracters without reinforcement, nega-
tive distracters with reinforcement) × time (12 TRs) interaction
during negative distracters, and Figure 4 shows their anatom-
ical locations. Probing brain regions demonstrating a signifi-
cant reinforcement × time interaction indicated that the right
 8 Cerebral Cortex, 2019, Vol. 00, No. 00

Table 1 Brain regions demonstrating a distracter type × time interaction effect from the region-of-interest analysis

Region BA x y z Cluster Peak F-value Simple contrasts between conditions for the delay period

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Neg > No Neg > Neu Neu > No
Cohen’s d Cohen’s d Cohen’s d

Amyg (A) −23 −5 −15 365 2.33 0.25 0.29∗ —

Amyg (A) 23 −5 −15 358 2.68 0.43∗∗ 0.24 —
sgACC 25 −2 13 −9 17 5.52 0.44∗∗ 0.29∗ —
vmPFC 10/11 2 48 −9 29 5.23 0.31∗ 0.11 —
vmPFC 11 −4 50 −11 72 6.05 0.38∗∗ 0.19 —
dmPFC 9/10 −8 60 34 1164 10.31 0.54∗∗ 0.28 —
VLPFC 45/47 −42 23 −15 527 6.16 0.41∗∗ 0.08 0.34∗∗
VLPFC 47 38 32 −12 54 5.02 0.37∗∗ 0.02 0.38∗∗
VLPFC 45 55 37 11 172 6.43 0.25 0.05 0.22
LFPC 10 32 59 10 263 5.4 −0.08 −0.18 —
LFPC 10 −36 51 7 70 4.42 0.03 −0.13 —
DLPFC 8/9 44 20 47 273 5.11 −0.17 −0.17 —
DLPFC 9 −42 25 38 268 6.97 0.09 −0.08 —

∗ P < 0.05 uncorrected.

∗∗ P < 0.05 FDR corrected.
Note: A = anatomically defined region; Neg = negative; Neut = neutral; No = no distracter; Amyg - amygdala; sgACC - subgenual anterior cingulate cortex; vmPFC -
ventromedial prefrontal cortex; dmPFC - dorsomedial prefrontal cortex; VLPFC - ventrolateral prefrontal cortex; LFPC - lateral frontopolar cortex; DLPFC - dorsolateral
prefrontal cortex; BA - Brodmann area.

amygdala, right dmPFC, left dmPFC, left VLPFC (BA 45), and left
VLPFC (BA 47) were less active during trials with reinforcement
relative to trials without reinforcement (see Fig. 4, FDR < 0.05).
DLPFC activation did not differ with reinforcement relative to tri-
als without reinforcement during the delay period (FDR > 0.05).
However, sensitivity analyses did indicate that early in the delay
period (8-s postmemoranda onset), the DLPFC was significantly
deactivated during trials without reinforcement, relative to tri-
als with reinforcement (i.e., relatively greater activation with
reinforcement relative to without reinforcement). During the
later delay period (10–14 s postmemoranda onset), there were no
significant differences during trials with reinforcement versus
trials without reinforcement (P > 0.10). Secondary analyses indi-
cated similar differences between reinforcement conditions for
the neutral distracters with the exception of the amygdala and
relatively few differences for no distracters (see Supplemental
Fig. S1).
Brain-Behavior Associations
Examination of Accuracy/Amygdala Associations During Negative
Distracters
As show in Figure 5, increased right amygdala activation
during correct trials predicted worse behavioral accuracy across
reinforcement conditions, β = −0.22, SE = 0.10, F(1,90) = 5.05,
P = 0.027, (reinforcement condition, F(1,51) = 4.51, P = 0.039;
reinforcement condition × right amygdala interaction, P > 0.10).
The left amygdala was not associated with behavioral accu-
racy, β = −0.11, SE = 0.10, F(1,85) = 1.35, P = 0.248 (reinforcement
condition, F(1,49) = 6.48, P = 0.014; reinforcement condition × left
amygdala interaction P > 0.10).
Examination of Reaction Time/Amygdala Associations During
Negative Distracters
Activation in the right amygdala to correct trials was not
associated with reaction time, β = 0.06, SE = 0.08, F(1,76) = 0.48,
P = 0.492 (reinforcement condition, F(1,51) = 31.64, P < 0.001;
reinforcement condition × right amygdala interaction P > 0.10).
The association between left amygdala activation and reaction
time varied as a function of condition, F(1,62) = 6.81, P = 0.011. As
shown in Figure 5, increased left amygdala activation was asso-
ciated with slower reaction times in the positive reinforcement
condition, β = 0.33, SE = 0.09, t(48) = 3.41, P = 0.001, whereas left
amygdala activation was not associated with reaction times
in the without reinforcement condition, β = −0.02, SE = 0.09,
t(48) = −0.22, P = 0.827 (condition F(1,48) = 32.22, P < 0.001; left
amygdala F(1,63) = 5.01, P = 0.029).
Examination to Determine If Changes in Right Amygdala Activation
Resulting from Positive Reinforcement Mediate Changes in Accuracy
Resulting From Positive Reinforcement
Controlling for the effect of reinforcement and average right
amygdala activation, decreases in right amygdala activation as
a function of reinforcement were not associated with improve-
ments in accuracy occurring due to reinforcement (see Table 3).
Consistently, tests of the indirect effect indicated that changes in
right amygdala activation as a function of reinforcement did not
mediate changes in behavioral accuracy due to reinforcement
(indirect effect = −0.13, Monte Carlo Standard Error (MCSE) = 0.83,
97.6% Monte Carlo Confidence Interval (MCCI) [−2.18, 1.91]).
As shown in Table 3, time sensitivity analyses did not indicate
that sustained right amygdala activation (10–14 s postmem-
oranda onset) was a stronger mediator than right amygdala
activation 8–16 s postmemoranda onset (indirect effect = −0.73,
MCSE = 1.34, 97.6% MCCI [−4.05, 2.30]).
Examination to Determine If Changes in Right Amygdala Activation
Resulting from Positive Reinforcement Mediate Changes in Accuracy
Resulting from Positive Reinforcement
Controlling for the effect of reinforcement and average right
amygdala activation, decreases in right amygdala activation as
a function of reinforcement were not associated with improve-
ments in accuracy occurring due to reinforcement (see Table 3).
Consistently, tests of the indirect effect indicated that changes in
right amygdala activation as a function of reinforcement did not
mediate changes in behavioral accuracy due to reinforcement
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Figure 3. Task-evoked time courses of anatomically extracted amygdala and PFC regions on correct trials. Event-related time courses for prefrontal regions are shown
based on the distracter type (no distracter, neutral distracter and negative distracter) × time (12 TRs) interaction region-of-interest analysis. Activation maps highlight
significant interactions (voxel-wise threshold of P < 1 × 10−7 , and an extent threshold of 15 voxels) overlaid on the skull stripped Colin brain (ch2better.nii). Plots show
changes in mean parameter estimates for average activation for the baseline/no distracter (black), neutral distracter (blue), and negative distracter (red) conditions.
Bar graphs ref lect mean parameter estimates during the delay period (8–16 s postmemoranda onset) for each distracter type. Bars with different letters differ at
FDR q < 0.05. Bars with a †differ at P < 0.05 uncorrected for multiple comparisons. The gray rectangular boxes above the x-axis indicate the onset and duration of the
memoranda, distracters, postdistracter fixation, and probe. dmPFC - dorsomedial prefrontal cortex; sgACC - subgenual anterior cingulate cortex; vmPFC - ventromedial
prefrontal cortex; LFPC - lateral frontopolar cortex; VLPFC - ventrolateral prefrontal cortex; DLPFC - dorsolateral prefrontal cortex; BA - Brodmann area; a.u. - arbitrary
units; L. - left; R. - Right.

(indirect effect = −0.13, MCSE = 0.83, 97.6% MCCI [−2.18, 1.91]). As
shown in Table 3, time sensitivity analyses did not indicate that
sustained right amygdala activation (10–14 s postmemoranda
onset) was a stronger mediator than right amygdala acti-
vation 8–16 s postmemoranda onset (indirect effect = −0.73,
MCSE = 1.34, 97.6% MCCI [−4.05, 2.30]).
Examination to Determine If Changes in Left Amygdala Activation
Resulting from Positive Reinforcement Mediate Changes in Reaction
Times Resulting from Positive Reinforcement
Controlling for the effect of reinforcement condition and average
left amygdala activation, participants who exhibited a decrease
in left amygdala activation as a function of reinforcement
demonstrated marginally faster reaction times in the with rein-
forcement compared with without reinforcement conditions
(see Table 3 and Fig. 6A). However, tests of the indirect effects
indicated that changes in left amygdala activation as a function
of reinforcement did not mediate changes in reaction times
due to reinforcement (indirect effect = 11.19, MCSE = 8.84, 97.6%
MCCI [−3.92, 36.11]). As shown in Table 3, timing sensitivity
analyses indicated that change in amygdala activation due
to reinforcement in the 10–14 s window mediated change
in reaction time due to reinforcement (indirect effect = 22.69,
MCSE = 12.49, 97.6% MCCI [0.77, 56.38]). As shown in Figure 6B,
participants who experienced a decrease in left amygdala
activation as a function of reinforcement demonstrated faster
reaction times in the with reinforcement compared with
without reinforcement conditions.
Discussion
The goals of the current study were to 1) determine whether
patterns of fronto-limbic activation occurring in the context of
resisting emotional interference seen in adults are present in
young adolescents and 2) test the extent to which providing
positive reinforcement would modulate fronto-limbic systems
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Figure 4. Task-evoked time courses of anatomically extracted amygdala and PFC regions on correct trials. Event-related time courses for prefrontal regions are shown
based on the negative distracters condition (with and without positive reinforcement) by time (12 TRs) interaction region-of-interest analysis. Activation maps highlight
significant interactions (voxel-wise threshold of P < 1 × 10−3 , and an extent threshold of 75 voxels) overlaid on the skull stripped Colin brain (ch2better.nii). Plots show
changes in mean parameter estimates for average activation for the with reinforcement (green) and without reinforcement (red) conditions. Bar graphs ref lect mean
parameter estimates during the delay period (8—16 s postmemoranda onset) for each reinforcement condition. Bars with different letters differ at FDR q < 0.05. Bars with
a †differ at P < 0.05 uncorrected for multiple comparisons. The gray rectangular boxes above the x-axis indicate the onset and duration of the memoranda, distracters,
postdistracter fixation, probe, and feedback. dmPFC - dorsomedial prefrontal cortex; DLPFC - dorsolateral prefrontal cortex; VLPFC - ventrolateral prefrontal cortex; BA
- Brodmann area; a.u. = arbitrary units; L - left; R - right; W/R.: with reinforcement; W/O R.: without reinforcement.

Table 2 Comparisons of BOLD signal during correct trials of the EDWM task: effect of reinforcement × time interaction for negative distracter
trials

Region BA x y z Cluster Maximum Simple contrasts between conditions

F-value for the delay period W/R. < W/O R.

Amygdala (A) −23 −5 −15 365 1.26 0.28∗

Amygdala (A) 23 −5 −15 358 1.39 0.41∗∗
dmPFC 9 −2 52 31 373 5.65 0.70∗∗
dmPFC 10 2 53 14 114 4.42 0.51∗∗
VLPFC 47 −46 23 −13 209 5.37 0.49∗∗
VLPFC 45 −59 22 16 110 4.46 0.58∗∗
DLPFC 8 −44 27 43 142 4.5 0.13NS

∗ P < 0.05 uncorrected.

∗∗ P < 0.05 FDR corrected.
Note: A = anatomically defined region; W/R. = with reinforcement; W/O R. = without reinforcement; L = left; R = right. dmPFC - dorsomedial prefrontal cortex;
VLPFC - ventrolateral prefrontal cortex; DLPFC - dorsolateral prefrontal cortex; BA - Broadman Area.

to reduce emotional interference and associated declines
in goal-directed behavior. Main findings from the first goal
suggest that typically developing youth exhibit largely similar
patterns of behavioral performance, neural activity, and brain-
behavior associations as those documented in adults during
emotional interference. In particular, we found that: 1) WM
was more impaired by emotional distracters relative to neutral
and no distracters; 2) emotional distracters were associated
with increased activation in the amygdala, and VLPFC, and
decreased DLPFC activation relative to no distracters; and 3)
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Figure 5. Individual differences in WM performance as a function of average amygdala activation 8–16 s postmemoranda onset. (A) The main effect of right amygdala
activation on WM accuracy (percent correct) across reinforcement conditions. (B) The simple slopes depicting the nature of the significant amygdala × reinforcement
condition interaction on WM reaction times. W/R. - with reinforcement; W/O R. - without reinforcement.

Table 3 Change in amygdala activation due to reinforcement as a mediator of performance for different windows within the delay period

DV Predictor(s) Delay period (8–16 s) Delay period (10–14 s)

B 97.6% CI B 97.6% CI

Eq. 1 Accuracy Condition −5.47∗ (−9.76, −1.17) −5.47∗ (−9.76, −1.17)

Eq. 2 Right Amyg Condition 0.03∗ (0.00, 0.05) 0.04∗ (0.02, 0.06)
Eq. 3 Accuracy Condition −5.34∗ (−10.09, −0.58) −4.73∗ (−10.08, 0.60)
 Right Amyg −5.23 (−78.13, 67.67) −17.99 (−93.77, 58.00)
x Right Amyg 7.74 (−98.38, 113.86) −7.78 (−107.70, 92.14)
Eq. 3 R2 0.04 0.01
Eq. 3 F 0.03 0.18

Eq. 1 Reaction Time Condition 140∗ (88.3, 192.0) 140∗ (88.3, 192.0)
Eq. 2 L. Amyg Condition 0.02∗ (0.00, 0.05) 0.04∗ (0.01, 0.07)
Eq. 3 Reaction Time Condition 129∗ (76.5, 181.4) 117∗ (63.6, 171.3)
 Left Amyg 496∗ (−179.7, 1172.6) 628∗ (50.0, 1206.0)
x Left Amyg −1037 (−2344.2, 270.7) −479 (−1623.6, 665.9)
Eq. 3 R2 0.10 0.12
Eq. 3 F 2.70∗ 3.30∗

Note: ∗ P < 0.050. Amyg = Amygdala. Eq. = equation. Condition = without reinforcement—with reinforcement.

individual differences in the degree of WM impairment due to
emotional distracters were associated with increased amygdala
activation. Findings from our second goal suggest that positive
reinforcement can improve WM performance and can modulate
fronto-limbic systems involved in emotional interference.
Specifically, we found that: 1) positive reinforcement for correct
responding was associated with both higher accuracy and
faster reaction times across all distracter types; 2) positive
reinforcement was associated with decreased activation in the
right amygdala, left VLPFC and bilateral dmPFC, and increased
DLPFC activation (8-s postmemoranda onset) relative to
non-reinforced responding during the presentation of negative
distracters; 3) amygdala activation was associated with lower
WM accuracy (right amygdala) across reinforcement conditions,
and slower reaction times for trials with reinforcement (left
amygdala); and 4) decreases in sustained left amygdala
activation (10–14 s postmemoranda onset) mediated observed
decreases in reaction times. These findings are discussed in
further detail below.
Neural Networks Underlying Emotional Interference
Our results are supportive of our primary goal to replicate and
further clarify the neural networks underlying resistance to
emotional interference in adolescents. Consistent with the
extant literature in adults and a recent study in adolescence,
 12 Cerebral Cortex, 2019, Vol. 00, No. 00
Figure 6. Within participant mediation model testing whether changes in left
amygdala activation is a mediator of positive reinforcement induced changes
in WM reaction times. (A) Changes in average amygdala activation 8–16 s post-
memoranda onset as the potential mediator. (B) Changes in sustained amygdala
(10–14 s postmemoranda onset) as the potential mediator. c, total effect; c ,
direct effect; IE, indirect effect. W/R. - with reinforcement; W/O R. - without
reinforcement.
we observed that emotional interference is associated with
increased activation in the ventral visual stream (see Supple-
mental Table S1 and Fig. S2), and the amygdala (Iordan et al.
2013; Vetter et al. 2015; Hung et al. 2018; Schweizer et al. 2019).
In this context, increased ventral visual stream and amygdala
activation to negative distracters likely reflects the bottom-up
detection of highly salient emotional information. In addition,
we also observed increased sgACC activation to negative
distracters, which might reflect the conscious processing of
negative emotional stimuli (Laxton et al. 2013; Huebl et al.
2016). The motivational salience of the IAPS images was likely
determined by the dmPFC, whose activity has been shown
to support the representation, evaluation, and extraction of
emotional information from affective stimuli (Taylor et al. 2003;
Kober et al. 2008; Peelen et al. 2010; Etkin et al. 2011; Skerry and
Saxe 2014). Based on the graduated pattern of activation in the
dmPFC, it can be inferred that negative distracters were coded
as more motivationally salient than neutral or no distracters,
and hence, are likely to cause interference. Consistent with this
interpretation, negative distracters were associated with greater
impairment in WM accuracy than neutral and no distracters and
slowed reaction times more than the no distracter condition.
Furthermore, individuals with greater right amygdala activation
in response to negative distracters demonstrated lower WM
accuracy. Thus, individuals for whom negative distracters
were affectively salient were more susceptible to emotional
interference.
We observed evidence that the aforementioned bottom-up
processes were concurrently associated with the modulation of
brain regions supporting the top-down management of com-
peting goals, specifically in the LFPC and DLPFC. A recently
articulated framework of frontopolar cortex function (Mansouri
et al. 2017) posits that the medial frontopolar cortex tracks
the value of the stimulus, which enables the ability to disen-
gage cognitive control from the current task and to redistribute
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resources to processing other goals of greater value. The grad-
uated activation pattern in the vmPFC following the onset of
negative distracters (i.e., alternate goals) suggests that nega-
tive distracters were being monitored as motivationally salient
events that warranted exploration (Dolcos et al. 2004). According
to the theory, these goals would have competed for primacy in
WM, where the LFPC is hypothesized to enable the monitoring of
several competing goals in order to facilitate the re-engagement
of one as a replacement of the current goal if indicated, whereas
the DLPFC is thought to recruit and implement cognitive con-
trol to optimize the performance of the current goal (Mansouri
et al. 2017). As such, decreased LFPC and DLFC activation may
reflect the “hijacking” of attentional resources by motivationally
salient emotional stimulus (i.e., a competing goal). Interest-
ingly, the time-course of activation indicates that the deacti-
vation observed at 8-s postmemoranda onset was followed by
a subsequent BOLD response, potentially reflecting processing
of the distracter in WM, which was followed by another BOLD
response corresponding to the onset of the probe (see Fig. 3).
This pattern of deactivation then reactivation is consistent with
the neurocomputational model of LFPC neuronal functioning
when cognitive branching, i.e., perform tasks related to one goal,
while keeping in WM information related to a secondary goal
that needs to completed (Koechlin and Hyafil 2007). During the
branching processes, it is possible that memoranda could be lost
resulting in decreased WM accuracy (Anticevic et al. 2010). These
findings replicate previous results in both adults (Anticevic et al.
2010; Iordan et al. 2013; Vetter et al. 2015; Hung et al. 2018;
Schweizer et al. 2019) and adolescents (Vetter et al. 2015).
We also observed increased activation in the VLPFC to dis-
tracters (neutral and negative) relative to no distracter trials,
which is consistent with this region’s hypothesized role in the
top-down inhibition of emotional interference as indicated by
its negative associations with subjective distractibility and emo-
tionality of negative affective stimuli (Dolcos and McCarthy
2006; Iordan et al. 2013). Consistent with this interpretation,
reaction times were slower and WM accuracy was lower when
neutral distracters and negative distracters were presented ver-
sus no distracters (Anticevic et al. 2010; Ladouceur et al. 2018).
Thus, overall our findings are consistent with the emerg-
ing literature on emotional interference in adolescents which
indicate that adults and young adolescents activate compara-
ble networks underlying resistance to emotional interference.
Future work is needed to determine the temporal sequencing
of activation within identified regions to further elucidate the
functional network underlying emotional interference.
The Impact of Positive Reinforcement on Emotional
Interference
Our results also provided strong support for a second goal to
evaluate the extent to which providing positive reinforcement
would modulate fronto-limbic systems to reduce emotional
interference and associated declines in goal-directed behavior.
Our behavioral results indicated that positive reinforcement
increased accuracy and decreased reaction times across all
distracter types, which indicates that it nonspecifically reduced
interference from all distracters. These results are consistent
with neuropsychological studies showing that WM performance
is faster and more accurate when it is rewarded than when
 Emotional Interference in Adolescence
positive reinforcement is absent or low. At the neural level,
we observed that positive reinforcement of correct responding
resulted in reduced activation in the right amygdala, left
VLPFC, and bilateral dmPFC. As previously described, these
aforementioned regions were specifically elevated during
processing of emotional relative to no distracter trials. Decreases
in these regions are consistent with decreased processing of
the negative emotional stimuli such that they were no longer
salient and did not require the recruitment of inhibitory control,
or appraisal. These findings are consistent with our preliminary
study (Ladouceur et al. 2018), but contrary to the results of a
recent meta-analytic study (Parro et al. 2017), which observed
increased activation in the fronto-parietal cognitive control
network regions under conditions of positive reinforcement.
Of note, most of the previous studies examined the impact
of reward on cognitive control in the absence of negative
emotional images and most were conducted in adults. Few
studies have examined the impact of reward on negative
distracter processing in youth (Kaltwasser et al. 2013; Wei and
Kang 2014; Padmala et al. 2017; Ladouceur et al. 2018). The
only other neuroimaging study to date reported decreased
activation in the lateral occipital cortex, anterior insula, and
dorsal anterior cingulate during cued reward trials, which was
interpreted to reflect that reward decreased the processing
of negative emotional distracter images (Padmala et al. 2017).
However, in Padmala et al. (2017), amygdala functioning was not
modulated by reward. In contrast, in the current investigation,
not only was amygdala activation modulated by reward, but
also the magnitude of the decrease in left amygdala activation
observed as a function of reinforcement mediated the observed
speeding up of decision response times to the WM probe.
These findings are consistent with data demonstrating an
attenuation of amygdala activation and improved WM accuracy
when attention is directed toward nonemotional details of
negative internal distracters (i.e., negative memories) relative
to the emotional aspects of negative memories in the context
of an EDWM task (Iordan et al. 2019). Similarly, attenuation
of the amygdala response to negative images has also been
observed when visual attention is consumed elsewhere, even
when the control of visual attention does not require large
shifts in the visual field (Pessoa et al. 2002). Thus, positive
reinforcement appears to have altered the impact of negative
emotional distracters through attentional filtering (Vuilleumier
2005; Iordan et al. 2019). Consistent with this interpretation,
we observed that positive reinforcement was associated with
decreased activation in the lateral occipital cortex during the
delay period (see Supplementary Fig. S3). However, we did
not observe increased activation in fronto-parietal regions
implicated in top-down attentional modulation under reinforce-
ment; this may have been due to type II error resulting from
conservative statistical thresholding. Alternatively, attending
to a nonemotional portion of the negative images may have
required the same level of attentional control as processing the
negative images resulting in no differences in fronto-parietal
activation as a function of condition. Unfortunately, we did
not collect eye-tracking during the task, which would have
clarified where participants were focusing their attention during
the positive reinforcement condition. It is also possible that
increased dopamine resulting from reinforcement resulted
in enhanced spatial tuning for the memoranda and the
suppression of processing negative images (Vijayraghavan et al.
2007). However, this cannot be verified given that we did not
alter or directly assess dopaminergic functioning.
Jones etal. 13
Of note, unlike previous investigations (e.g., Padmala and
Pessoa 2011; Padmala et al. 2017) examining the impact of rein-
forcement on cognitive control, we did not observe increases
Downloaded from https://academic.oup.com/cercor/advance-article-abstract/doi/10.1093/cercor/bhz266/5669895 by Brunel University London user on 09 December 2019
in the ventral striatum or other reward-related regions during
the task. This may have occurred because of differences in task
design. Specifically, participants were told prior to a block of
trials whether or not the upcoming block was a reward block
or a nonreward block. The blocked design is likely to instantiate
the slow tonic release of dopamine likely to facilitate sustained
attention processing (Schultz 2016). In contrast, studies that
have employed a cue to indicate reward versus nonreward trials
within a block and where there is increased uncertainty whether
or not the reward would be received (i.e., greater uncertainty
about whether or not the participant is likely to get the trial
correct) more reliably demonstrate activation within the ven-
tral striatum (e.g., Padmala and Pessoa 2011; Padmala et al.
2017). These types of designs with trial-specific cues may more
strongly instantiate the phasic release of dopamine resulting
in a better ability to detect BOLD activation within dopamine
producing brain regions using fMRI (Schultz 2016). Importantly,
the only other identified study employing this blocked approach
only detected changes in reward-related regions when individ-
ual differences in sensitivity to reward were examined (Locke
and Braver 2008). Future studies are needed to examine the
impact of task design differences and individual differences
in sensitivity to reward on cognitive control in the context of
preventing emotional interference (cf., Beck et al. 2010).
We also observed differential associations between WM per-
formance and activation in the left versus right amygdala. There
is no settled understanding of hemispheric specialization within
the amygdala. Some evidence suggests that the left amygdala is
more involved in processing threat, emotional arousal, salience,
and sustained emotional processing (Phelps et al. 2001; Baas
et al. 2004; Costanzo et al. 2015). Whereas the right amygdala
has been implicated in processing animal stimuli, emotional
ambiguity and unconscious emotional information (Baas et al.
2004;Mormann et al. 2011 ; Wang et al. 2017). It is possible that
left amygdala activation was associated with slower reaction
times because anxiety is more likely to interfere with processing
efficiency (i.e., reaction times) rather than accuracy (Eysenck
et al. 2007). In contrast, greater right amygdala activation may
indicate that individuals who were more effected by the neg-
ative IAPS images pertaining to animals experienced greater
emotional interference causing participants to respond incor-
rectly (Mormann et al. 2011; Wang et al. 2017). These supposi-
tions should be taken with caution, especially in light of recent
research demonstrating that the choice of motion correction and
smoothing parameters can also have a strong impact of whether
bilateral, or hemispheric specific activation is found (Murphy
et al., 2019).
Limitations
The findings of the current study should be interpreted in light
of the following limitations. First, there was a significant loss of
fMRI data (∼50%) due to excessive movement and poor behav-
ioral accuracy. This data loss likely occurred due to the age
of participants combined with relatively long duration of the
task (30 min). This attrition may limit the generalizability of the
findings to youth with the capacity to stay still for longer periods
of time. Second, we were unable to include sufficient trials to
be able to model both correct and incorrect responding given
the constraints of time, thus limiting our ability to examine
 14 Cerebral Cortex, 2019, Vol. 00, No. 00
task differences associated with performance. Third, we did
not collect measures related to the subjective distractibility of
the distracters, limiting our ability to draw strong inferences
related to VLPFC functioning. Finally, findings are limited to the
effects of negative distracters and to early adolescence. Follow-
up assessments are under way and will provide clues as to
whether these findings can be generalized to older adolescents.
Conclusions
In summary, findings from this study provide evidence indicat-
ing that the patterns of neural activation in fronto-limbic regions
associated with emotional interference obtained with adults
are also present in young adolescents. This study also demon-
strates that positive reinforcement (i.e., monetary rewards for
correct responses) can be used to modulate fronto-limbic sys-
tems associated with resisting emotional distraction. Specifi-
cally, we show that positive reinforcement generally improves
task performance and reduces activation in limbic, medial, and
ventrolateral PFC regions in a group of healthy youth. Impor-
tantly, findings demonstrate, for the first time, that the modula-
tion of amygdala activation by reinforcement mediates changes
in behavior. Future research examining the effective connectiv-
ity of key regions (e.g., the amygdala, VLPFC, vmPFC and lateral
occipital cortex) within the network and testing interactions
with age, which have been shown to be associated with changes
in attentional control (Luna et al. 2010) and reward processing
(de Macks et al. 2011), respectively, will provide further knowl-
edge about the possible underlying mechanisms. It will also
be possible to examine to extent to which age-related changes
in functional connectivity between the ventral striatum and
VLPFC in trials with reinforcement (Davidow et al. 2018) may
underlie the impact of reinforcement on emotional interference.
Such research will determine the extent to which it may be
possible to harness adolescent neural response to the effects of
positive reinforcement on PFC function to counteract negative
environmental influences and facilitate coping.
Supplementary Material
Supplementary material can be found at Cerebral Cortex online.
Funding
National Institute of Mental Health (R01MH099007; PI: Ladouceur);
National Institutes of Health (UL1TR001857).
Notes
The authors would like to thank Drs. Anticevic and Barch for
allowing them to adapt the EDWM task for adolescents and for
their feedback on the design of the study. They also thank the
Pitt Clinical and Translational Science Institute (CTSI) for their
help with recruitment as well as the children and their families
for participating in this research study. Conflict of Interest: None
declared.
References
American Psychiatric Association. 1994. Diagnostic and Statistical
Manual of Mental Disorders. Washington, DC: American Psychi-
atric Association.
Anderson AK, Phelps EA. 2001. Lesions of the human amygdala
impair enhanced perception of emotionally salient events.
Nature. 411:305–309.
Downloaded from https://academic.oup.com/cercor/advance-article-abstract/doi/10.1093/cercor/bhz266/5669895 by Brunel University London user on 09 December 2019
Anticevic A, Barch DM, Repovs G. 2010. Resisting emotional inter-
ference: brain regions facilitating working memory perfor-
mance during negative distraction. Cogn Affect Behav Neurosci.
10:159–173.
Anticevic A, Repovs G, Barch DM. 2011. Working memory
encoding and maintenance deficits in schizophrenia: neu-
ral evidence for activation and deactivation abnormalities.
Schizophr Bull. 39:168–178.
Armony JL, Dolan RJ. 2002. Modulation of spatial attention by
fear-conditioned stimuli: an event-related fMRI study. Neu-
ropsychologia. 40:817–826.
Attneave F, Arnoult MD. 1956. The quantitative study of shape
and pattern perception. Psychol Bull. 53:452.
Baas D, Aleman A, Kahn RS. 2004. Lateralization of amygdala
activation: a systematic review of functional neuroimaging
studies. Brain Res Rev. 45:96–103.
Bahlmann J, Aarts E, D’Esposito M. 2015. Influence of motivation
on control hierarchy in the human frontal cortex. J Neurosci.
35:3207–3217.
Beck SM, Locke HS, Savine AC, Jimura K, Braver TS. 2010. Primary
and secondary rewards differentially modulate neural activ-
ity dynamics during working memory. PLoS One. 5:e9251.
Benjamini Y, Hochberg Y. 1995. Controlling the false discovery
rate: a practical and powerful approach to multiple testing. J
Royal Stat Soc. 57:289–300.
Benjamini Y, Yekutieli D. 2001. The control of the false dis-
covery rate in multiple testing under dependency. Ann Stat.
29:1165–1188.
Bradley MM, Lang PJ. 1994. Measuring emotion: the self-
assessment manikin and the semantic differential. J Behav
Ther Exp Psychiatry. 25:49–59.
Britton JC, Grillon C, Lissek S, Norcross MA, Szuhany KL, Chen G,
Ernst M, Nelson EE, Leibenluft E, Shechner T. 2013. Response
to learned threat: an fMRI study in adolescent and adult
anxiety. Am J Psychiatry. 170:1195–1204.
Bruening J, Ludwig VU, Paschke LM, Walter H, Stelzel C. 2018.
Motivational effects on the processing of delayed inten-
tions in the anterior prefrontal cortex. NeuroImage. 172:
517–526.
Casey BJ, Heller AS, Gee DG, Cohen AO. 2019. Development of the
emotional brain. Neurosci Lett. 693:29–34.
Colich NL, Ho TC, Foland-Ross LC, Eggleston C, Ordaz SJ, Singh
MK, Gotlib IH. 2017. Hyperactivation in cognitive control and
visual attention brain regions during emotional interference
in adolescent depression. Biol Psychiatry Cogn Neurosci Neu-
roimaging. 2:388–395.
Collin CA, McMullen PA. 2002. Using Matlab to generate families
of similar Attneave shapes. Behav Res Methods Instrum Comput.
34:55–68.
Costanzo EY, Villarreal M, Drucaroff LJ, Ortiz-Villafañe M, Castro
MN, Goldschmidt M, Wainsztein AE, Ladrón-de-Guevara MS,
Romero C, Brusco LI. 2015. Hemispheric specialization in
affective responses, cerebral dominance for language, and
handedness: lateralization of emotion, language, and dexter-
ity. Behav Brain Res. 288:11–19.
Cox RW, Reynolds RC, Taylor PA. 2016. AFNI and clustering: false
positive rates redux. bioRxiv, p. 065862.
Davidow JY, Insel C, Somerville LH. 2018. Adolescent devel-
opment of value-guided goal pursuit. Trends Cogn Sci.
22:725–736.
 Emotional Interference in Adolescence
de Macks ZAO, Moor BG, Overgaauw S, Güroğlu B, Dahl RE, Crone
EA. 2011. Testosterone levels correspond with increased ven-
tral striatum activation in response to monetary rewards in
adolescents. Dev Cogn Neurosci. 1:506–516.
Denkova E, Wong G, Dolcos S, Sung K, Wang L, Coupland N,
Dolcos F. 2010. The impact of anxiety-inducing distraction
on cognitive performance: a combined brain imaging and
personality investigation. PLoS One. 5:e14150.
Dolcos F, Diaz-Granados P, Wang L, McCarthy G. 2008. Oppos-
ing influences of emotional and non-emotional distracters
upon sustained prefrontal cortex activity during a delayed-
response working memory task. Neuropsychologia. 46:326–335.
Dolcos F, Iordan A, Kragel J, Stokes J, Campbell R, McCarthy
G, Cabeza R. 2013. Neural correlates of opposing effects
of emotional distraction on working memory and episodic
memory: an event-related FMRI investigation. Front Psychol. 4:
293.
Dolcos F, Kragel P, Wang L, McCarthy G. 2006. Role of the inferior
frontal cortex in coping with distracting emotions. Neurore-
port. 17:1591–1594.
Dolcos F, LaBar KS, Cabeza R. 2004. Dissociable effects of arousal
and valence on prefrontal activity indexing emotional evalu-
ation and subsequent memory: an event-related fMRI study.
NeuroImage. 23:64–74.
Dolcos F, McCarthy G. 2006. Brain systems mediating cog-
nitive interference by emotional distraction. J Neurosci.
26:2072–2079.
Eklund A, Nichols TE, Knutsson H. 2016. Cluster failure: why
fMRI inferences for spatial extent have inflated false-positive
rates. Proc Natl Acad Sci U S A. 201602413.
Etkin A, Egner T, Kalisch R. 2011. Emotional processing in ante-
rior cingulate and medial prefrontal cortex. Trends Cogn Sci.
15:85–93.
Eysenck MW, Derakshan N, Santos R, Calvo MG. 2007. Anxiety
and cognitive performance: attentional control theory. Emo-
tion. 7:336.
Fusar-Poli P, Placentino A, Carletti F, Allen P, Landi P, Abbamonte
M, Barale F, Perez J, McGuire P, Politi PL. 2009. Laterality
effect on emotional faces processing: ALE meta-analysis of
evidence. Neurosci Lett. 452:262–267.
Gee DG, Humphreys KL, Flannery J, Goff B, Telzer EH,
Shapiro M, Hare TA, Bookheimer SY, Tottenham N. 2013.
A developmental shift from positive to negative connectiv-
ity in human amygdala-prefrontal circuitry. J Neurosci. 33:
4584–4593.
Guyer AE, Silk JS, Nelson EE. 2016. The neurobiology of the
emotional adolescent: from the inside out. Neurosci Biobehav
Rev. 70:74–85.
Huebl J, Brücke C, Merkl A, Bajbouj M, Schneider G-H, Kühn AA.
2016. Processing of emotional stimuli is reflected by modula-
tions of beta band activity in the subgenual anterior cingulate
cortex in patients with treatment resistant depression. Soc
Cogn Affect Neurosci. 11:1290–1298.
Hung Y, Gaillard SL, Yarmak P, Arsalidou M. 2018. Dissociations
of cognitive inhibition, response inhibition, and emotional
interference: Voxelwise ALE meta-analyses of fMRI studies.
Hum Brain Mapp. 39:4065–4082.
Iordan A, Dolcos F. 2017. Brain activity and network interactions
linked to valence-related differences in the impact of emo-
tional distraction. Cereb Cortex. 27:731–749.
Iordan A, Dolcos S, Dolcos F. 2013. Neural signatures of the
response to emotional distraction: a review of evidence from
brain imaging investigations. Front Hum Neurosci. 7:1.
Jones etal. 15
Iordan A, Dolcos S, Dolcos F. 2019. Brain activity and network
interactions in the impact of internal emotional distraction.
Cereb Cortex. 29:2607–2623.
Downloaded from https://academic.oup.com/cercor/advance-article-abstract/doi/10.1093/cercor/bhz266/5669895 by Brunel University London user on 09 December 2019
Jimura K, Locke HS, Braver TS. 2010. Prefrontal cortex mediation
of cognitive enhancement in rewarding motivational con-
texts. Proc Natl Acad Sci U S A. 107:8871–8876.
Jones NP, Chase HW, Fournier J. 2016. Brain mechanisms of
anxiety’s effects on cognitive control in major depressive
disorder. Psychol Med. 46:2397–2409.
Jones NP, Siegle GJ, Mandell D. 2015. Motivational and emotional
influences on cognitive control in depression: a pupillometry
study. Cogn Affect Behav Neurosci. 15:263–275.
Joormann J, Talbot L, Gotlib IH. 2007. Biased processing of emo-
tional information in girls at risk for depression. J Abnorm
Psychol. 116:135–143.
Judd CM, Kenny DA, McClelland GH. 2001. Estimating and testing
mediation and moderation in within-subject designs. Psychol
Methods. 6:115.
Kaltwasser L, Ries S, Sommer W, Knight R, Willems RM. 2013.
Independence of valence and reward in emotional word pro-
cessing: electrophysiological evidence. Front Psychol. 4:168.
Kober H, Barrett LF, Joseph J, Bliss-Moreau E, Lindquist K, Wager
TD. 2008. Functional grouping and cortical–subcortical inter-
actions in emotion: a meta-analysis of neuroimaging studies.
NeuroImage. 42:998–1031.
Koechlin E, Hyafil A. 2007. Anterior prefrontal function and the
limits of human decision-making. Science. 318:594–598.
Ladouceur CD. 2012. Neural systems supporting cognitive-
affective interactions in adolescence: the role of puberty and
implications for affective disorders. Front Integr Neurosci. 6:65.
Ladouceur CD, Dahl RE, Williamson DE, Birmaher B, Ryan ND,
Casey B. 2005. Altered emotional processing in pediatric anx-
iety, depression, and comorbid anxiety-depression. J Abnorm
Child Psychol. 33:165–177.
Ladouceur CD, Diwadkar VA, White R, Bass J, Birmaher B, Axel-
son DA, Phillips ML. 2013. Fronto-limbic function in unaf-
fected offspring at familial risk for bipolar disorder during
an emotional working memory paradigm. Dev Cogn Neurosci.
5:185–196.
Ladouceur CD, Schlund MW, Segreti A-M. 2018. Positive
reinforcement modulates fronto-limbic systems subserv-
ing emotional interference in adolescents. Behav Brain Res.
338:109–117.
Ladouceur CD, Silk JS, Dahl RE, Ostapenko L, Kronhaus DM,
Phillips ML. 2009. Fearful faces influence attentional control
processes in anxious youth and adults. Emotion. 9:855–864.
Lang PJ, Bradley MM, Cuthbert BN. 1999. International Affective
Picture System (IAPS): Instruction Manual And Affective Ratings.
The Center for Research in Psychophysiology: University of
Florida.
Lang PJ, Bradley MM, Cuthbert BN. 2008. International Affective
Picture System (IAPS): Affective Ratings of Pictures and Instruction
Manual. Technical Report A-8. Gainesville, FL: University of
Florida.
Laxton AW, Neimat JS, Davis KD, Womelsdorf T, Hutchison WD,
Dostrovsky JO, Hamani C, Mayberg HS, Lozano AM. 2013. Neu-
ronal coding of implicit emotion categories in the subcallosal
cortex in patients with depression. Biol Psychiatry. 74:714–719.
LeDoux JE. 2000. Emotion circuits in the brain. Annu Rev Neurosci.
23:155–184.
Locke HS, Braver TS. 2008. Motivational influences on cogni-
tive control: behavior, brain activation, and individual differ-
ences. Cogn Affect Behav Neurosci. 8:99–112.
 16 Cerebral Cortex, 2019, Vol. 00, No. 00
Luna B, Padmanabhan A, O’Hearn K. 2010. What has fMRI told us
about the development of cognitive control through adoles-
cence? Brain Cogn. 72:101–113.
Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH. 2003. An auto-
mated method for neuroanatomic and cytoarchitectonic
atlas-based interrogation of fMRI data sets. NeuroImage.
19:1233–1239.
Mansouri FA, Koechlin E, Rosa MG, Buckley MJ. 2017. Managing
competing goals-a key role for the frontopolar cortex. Nat Rev
Neurosci. 18:645.
Mazaika PK, Whitfield S, Cooper JC. 2005. Detection and repair of
transient artifacts in fMRI data. NeuroImage. 26:S36.
McManis MH, Bradley MM, Berg WK, Cuthbert BN, Lang PJ. 2001.
Emotional reactions in children: verbal, physiological, and
behavioral responses to affective pictures. Psychophysiology.
38:222–231.
Mogg K, McNamara J, Powys M, Rawlinson H, Seiffer A, Bradley
BP. 2000. Selective attention to threat: a test of two cognitive
models of anxiety. Cognit Emot. 14:375–399.
Monk CS, Telzer EH, Mogg K, Bradley BP, Mai X, Louro HM, Chen
G, McClure-Tone EB, Ernst M, Pine DS. 2008. Amygdala and
ventrolateral prefrontal cortex activation to masked angry
faces in children and adolescents with generalized anxiety
disorder. Arch Gen Psychiatry. 65:568–576.
Montoya AK, Hayes AF. 2017. Two-condition within-participant
statistical mediation analysis: a path-analytic framework.
Psychol Methods. 22:6.
Mormann F, Dubois J, Kornblith S, Milosavljevic M, Cerf M, Ison
M, Tsuchiya N, Kraskov A, Quiroga RQ, Adolphs R. 2011. A
category-specific response to animals in the right human
amygdala. Nat Neurosci. 14:1247.
Murphy JE, Yanes JA, Kirby LA, Reid MA, Robinson JL. 2019.
Left, right, or bilateral amygdala activation? How effects of
smoothing and motion correction on ultra-high field, high-
resolution functional magnetic resonance imaging (fMRI)
data alter inferences. Neurosci Res.
Narum SR. 2006. Beyond Bonferroni: less conservative analyses
for conservation genetics. Conserv Genet. 7:783–787.
Padmala S, Pessoa L. 2011. Reward reduces conflict by enhancing
attentional control and biasing visual cortical processing. J
Cogn Neurosci. 23:3419–3432.
Padmala S, Sirbu M, Pessoa L. 2017. Potential reward reduces the
adverse impact of negative distractor stimuli. Soc Cogn Affect
Neurosci. 12:1402–1413.
Parro C, Dixon ML, Christoff K. 2017. The neural basis of moti-
vational influences on cognitive control: an ALE meta-analysis.
bioRxiv.113126.
Peelen MV, Atkinson AP, Vuilleumier P. 2010. Supramodal rep-
resentations of perceived emotions in the human brain. J
Neurosci. 30:10127–10134.
Pessoa L. 2009. How do emotion and motivation direct executive
control? Trends Cogn Sci. 13:160–166.
Pessoa L. 2015. Précis on the cognitive-emotional brain. Behav
Brain Sci. 38:1–66.
Pessoa L, McKenna M, Gutierrez E, Ungerleider L. 2002. Neural
processing of emotional faces requires attention. Proc Natl
Acad Sci U S A. 99:11458–11463.
Phelps EA, O’Connor KJ, Gatenby JC, Gore JC, Grillon C, Davis M.
2001. Activation of the left amygdala to a cognitive represen-
tation of fear. Nat Neurosci. 4:437.
Phillips ML, Ladouceur C, Drevets W. 2008. A neural model of vol-
untary and automatic emotion regulation: implications for
understanding the pathophysiology and neurodevelopment
of bipolar disorder. Mol Psychiatry. 13:833–857.
Piech RM, McHugo M, Smith SD, Dukic MS, Van Der Meer J,
Abou-Khalil B, Most SB, Zald DH. 2011. Attentional capture
by emotional stimuli is preserved in patients with amygdala
Downloaded from https://academic.oup.com/cercor/advance-article-abstract/doi/10.1093/cercor/bhz266/5669895 by Brunel University London user on 09 December 2019
lesions. Neuropsychologia. 49:3314–3319.
Pochon JB, Levy R, Fossati P, Lehericy S, Poline JB, Pillon B, Le
Bihan D, Dubois B. 2002. The neural system that bridges
reward and cognition in humans: an fMRI study. Proc Natl
Acad Sci U S A. 99:5669–5674.
Schultz W. 2016. Dopamine reward prediction-error signalling: a
two-component response. Nat Rev Neurosci. 17:183.
Schweizer S, Satpute AB, Atzil S, Field AP, Hitchcock C, Black M,
Barrett LF, Dalgleish T. 2019. The impact of affective infor-
mation on working memory: a pair of meta-analytic reviews
of behavioral and neuroimaging evidence. Psychol Bull. 145:
566.
Shaffer D, Fisher P, Lucas CP, Dulcan MK, Schwab-Stone ME. 2000.
NIMH diagnostic interview schedule for children version IV
(NIMH DISC-IV): description, differences from previous ver-
sions, and reliability of some common diagnoses. J Am Acad
Child Adolesc Psychiatry. 39:28–38.
Siegle GJ, Steinhauer SR, Thase ME, Stenger VA, Carter CS. 2002.
Can’t shake that feeling: event-related fMRI assessment of
sustained amygdala activity in response to emotional infor-
mation in depressed individuals. Biol Psychiatry. 51:693–707.
Skerry AE, Saxe R. 2014. A common neural code for perceived
and inferred emotion. J Neurosci. 34:15997–16008.
Sternberg S. 1969. The discovery of processing stages: extensions
of Donders’ method. In: Koster WG, editor. Attention and Perfor-
mance. II Acta Psychologica. Vol 30. North Holland, Amsterdam,
pp. 276–315.
Taylor SF, Phan KL, Decker LR, Liberzon I. 2003. Subjective rat-
ing of emotionally salient stimuli modulates neural activity.
NeuroImage. 18:650–659.
Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F,
Etard O, Delcroix N, Mazoyer B, Joliot M. 2002. Automated
anatomical labeling of activations in SPM using a macro-
scopic anatomical parcellation of the MNI MRI single-subject
brain. NeuroImage. 15:273–289.
Vetter NC, Pilhatsch M, Weigelt S, Ripke S, Smolka MN.
2015. Mid-adolescent neurocognitive development of ignor-
ing and attending emotional stimuli. Dev Cogn Neurosci. 14:
23–31.
Vijayraghavan S, Wang M, Birnbaum SG, Williams GV, Arnsten
AF. 2007. Inverted-U dopamine D1 receptor actions on pre-
frontal neurons engaged in working memory. Nat Neurosci.
10:376–384.
Vuilleumier P. 2005. How brains beware: neural mechanisms of
emotional attention. Trends Cogn Sci. 9:585.
Wager TD, Phan KL, Liberzon I, Taylor SF. 2003. Valence, gender,
and lateralization of functional brain anatomy in emotion:
a meta-analysis of findings from neuroimaging. NeuroImage.
19:513–531.
Wang S, Yu R, Tyszka JM, Zhen S, Kovach C, Sun S, Huang Y,
Hurlemann R, Ross IB, Chung JM. 2017. The human amygdala
parametrically encodes the intensity of specific facial emo-
tions and their categorical ambiguity. Nat Commun. 8:14821.
Watanabe M. 1996. Reward expectancy in primate prefrental
neurons. Nature. 382:629.
Wei P, Kang G. 2014. Task relevance regulates the interaction
between reward expectation and emotion. Exp Brain Res.
232:1783–1791.
Woo C-W, Krishnan A, Wager TD. 2014. Cluster-extent based
thresholding in fMRI analyses: pitfalls and recommenda-
tions. NeuroImage. 91:412–419.