The nexus between decision making and emotion regulation: a review of convergent neurocognitive substrates.
ABSTRACT Emotional information, such as reward or punishment, gains rapid and often preferential access to neurocognitive resources. This ability to quickly evaluate and integrate emotion-related information is thought to benefit a range of behaviours critical for survival. Conversely, the improper use of, or preoccupation with, emotional information is associated with disruptions in functioning and psychiatric disorders. Optimally, an organism utilizes emotional information when it is significant, and minimizes its influence when it is not. Recently, similar regions of prefrontal cortex have been identified that are associated with regulating both behavioural conflict (motor response selection or inhibition) and affective conflict (emotional representation and awareness). In this review, data will be examined that concerns this convergence between decision making (modulating what we do) and emotion regulation (modulating how we feel) and an informal model will be proposed linking these processes at a neurocognitive level. The studies reviewed collectively support the conclusion that overlapping areas of prefrontal cortex perform similar computations whether the functional objective is to modulate an operant response, or an emotional one. Specifically, the idea is raised that key aspects of decision making and emotion regulation are bound by a common functional objective in which internal representations of conditioned stimuli and reinforcers are modulated to facilitate optimal behaviour or states. Emphasis is placed on dorsomedial, dorsolateral, ventrolateral, and ventromedial regions of prefrontal cortex.
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ABSTRACT: There is preliminary evidence to suggest that the prefrontal cortex (PFC) is modulated by sex steroids in humans and other primates. The current study examined whether sex differences in performance could be discerned on two working memory tasks that emphasize monitoring and updating processes, and on two tasks that engage the ventromedial PFC/orbitofrontal cortex (VMPFC/OFC). Healthy young adults (48 females; 45 males) completed the n-back, Self-Ordered Pointing (SOP), Iowa Gambling Task (IGT), and a probabilistic reversal learning task. On the IGT, males selected more cards from the advantageous decks than females. On the reversal learning task, there was no significant sex difference in acquisition of the reinforcement contingencies, but males made fewer errors than females during the reversal phase. The sexes did not differ significantly on the n-back or SOP tasks. These findings provide tentative support for the hypothesis that functions carried out by the VMPFC/OFC are sexually differentiated in humans. Copyright © 2014 Elsevier Inc. All rights reserved.Brain and Cognition 12/2014; 93C:42-53. · 2.82 Impact Factor
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ABSTRACT: Efficient implicit emotion regulation processes, which run without awareness, are important for human well-being. In this study, to investigate the influence of implicit emotion regulation on psychological and electrophysiological responses to gains and losses, participants were required to select between two Chinese four-character idioms to match the meaning of the third one before they performed a monetary gambling task. According to whether their meanings were related to emotion regulation, the idioms fell into two categories. Event-related potentials and self-rating emotional experiences to outcome feedback were recorded during the task. Priming emotion regulation reduced subjective emotional experience to both gains and losses and the amplitudes of the feedback-related negativity, while the P3 component was not influenced. According to these results, we suggest that the application of implicit emotion regulation effectively modulated the subjective emotional experience and the motivational salience of current outcomes without the cost of cognitive resources. This study implicates the potential significance of implicit emotion regulation in decision-making processes.Social Cognitive and Affective Neuroscience 10/2014; · 5.88 Impact Factor
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ABSTRACT: The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a "behavioral control" paradigm, which involves the ability to terminate a noxious stimulus, and a "safety signaling" paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings.PLoS ONE 01/2014; 9(12):e110654. · 3.53 Impact Factor
Behavioural Brain Research 217 (2011) 215–231
Contents lists available at ScienceDirect
Behavioural Brain Research
journal homepage: www.elsevier.com/locate/bbr
The nexus between decision making and emotion regulation: A review of
convergent neurocognitive substrates
Derek G.V. Mitchella,b,∗
aDepartment of Psychiatry and Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, Canada
bCentre for Brain and Mind, Department of Psychology, The University of Western Ontario, Canada
a r t i c l ei n f o
Received 25 June 2010
Received in revised form 19 October 2010
Accepted 22 October 2010
Available online 3 November 2010
a b s t r a c t
Emotional information, such as reward or punishment, gains rapid and often preferential access to
neurocognitive resources. This ability to quickly evaluate and integrate emotion-related information
is thought to benefit a range of behaviours critical for survival. Conversely, the improper use of, or pre-
occupation with, emotional information is associated with disruptions in functioning and psychiatric
disorders. Optimally, an organism utilizes emotional information when it is significant, and minimizes
its influence when it is not. Recently, similar regions of prefrontal cortex have been identified that are
conflict (emotional representation and awareness). In this review, data will be examined that concerns
this convergence between decision making (modulating what we do) and emotion regulation (modulat-
ing how we feel) and an informal model will be proposed linking these processes at a neurocognitive
emotional one. Specifically, the idea is raised that key aspects of decision making and emotion regulation
reinforcers are modulated to facilitate optimal behaviour or states. Emphasis is placed on dorsomedial,
dorsolateral, ventrolateral, and ventromedial regions of prefrontal cortex.
© 2010 Elsevier B.V. All rights reserved.
Ventrolateral prefrontal cortex .....................................................................................................................
2.1. Anatomical connections .....................................................................................................................
2.2. The role of vlPFC in decision making........................................................................................................
2.2.1.Negative feedback encoding.......................................................................................................
2.2.2. Motor response inhibition.........................................................................................................
2.2.4.Attention to behaviourally significant stimuli ....................................................................................
2.2.5.Summary and implications ........................................................................................................
2.3.VLPFC in emotion regulation ................................................................................................................
2.3.1.Negative emotion encoding .......................................................................................................
2.3.2.Emotional response inhibition ....................................................................................................
2.3.3.Emotional response modulation...................................................................................................
2.3.4.Attention to emotionally significant stimuli ......................................................................................
2.3.5.Summary and implications ........................................................................................................
2.4.Integrating vlPFC findings in decision
Abbreviations: mPFC, medial prefrontal cortex; vlPFC, ventrolateral prefrontal cortex; nACC, nucleus accumbens; dmPFC, dorsomedial prefrontal cortex; dlPFC, dorsolateral
prefrontal cortex; dACC, dorsal anterior cingulate cortex.
∗Corresponding author at: University Hospital, University of Western Ontario, 339 Windermere Road, London, Ontario, Canada.
E-mail address: firstname.lastname@example.org
0166-4328/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
making and emotion regulation..........................................................................................................................
3.Medial prefrontal cortex ............................................................................................................................
3.1.Anatomical connections .....................................................................................................................
3.2. The role of mPFC in decision making........................................................................................................
3.2.1. Reward encoding ..................................................................................................................
3.2.2.Expected outcome signalling ......................................................................................................
3.2.3. Extinction and related processes ..................................................................................................
3.2.4.Summary and implications ........................................................................................................
3.3. The role of mPFC in emotion regulation.....................................................................................................
3.3.1.Emotional modulation: extinction, reflection and augmentation ................................................................
3.3.2. Expected outcome signalling ......................................................................................................
3.3.3.Summary and implications ........................................................................................................
3.4. Integrating mPFC findings in decision making and emotion regulation....................................................................
4. Dorsomedial and dorsolateral prefrontal cortex....................................................................................................
4.1.Anatomical connections .....................................................................................................................
4.2.The role of dorsal prefrontal cortex in decision making ....................................................................................
4.2.1.Resolving decision conflict through attention.....................................................................................
4.2.2.Reinforcement encoding accounts ................................................................................................
4.3.The role of dorsal prefrontal cortex in emotion regulation .................................................................................
4.3.1.Resolving emotional conflict through attention ..................................................................................
4.3.2.Reappraisal strategy generation or maintenance .................................................................................
4.3.3.Summary and implications ........................................................................................................
4.4.Integrating dorsal prefrontal cortex findings in decision making and emotion regulation ................................................
Emotions have been described as states elicited by reinforcers,
and are thought to have evolved as an efficient means of influ-
encing behaviour . It makes sense, therefore, that the neural
(emotion regulation). Although implicit parallels are often drawn
from both literatures, the two areas of research have not been
well-integrated. Through the use of neuroimaging techniques and
data from human lesion studies, the striking similarity in anatomy
across the two lines of research is more apparent, and emerging
work is integrating aspects of each into the same experiments.
What has been lacking, however, is a systematic evaluation of
the specific neural regions across tasks, and a functional account
that would unify the roles for the common regions evoked by
these two processes. The purpose of this review is to illustrate
the areas of convergence and divergence in the functional neu-
roanatomy of decision making and emotion regulation. Special
attention will be paid to similarities and differences in the func-
tions ascribed to ventrolateral, medial, and dorsal prefrontal cortex
across these two contexts. A unified account will be proposed
based on a functional consensus of the decision making and emo-
tion regulation literature. This account differs from many previous
models of emotion regulation in that it argues for a specific role
of dorsal attention-related areas in modulating the influence of
motivational information on behaviour and emotion. Lastly, the
review will highlight areas that are currently controversial or
unresolved, and therefore indicate potential avenues for future
A comprehensive review of the large body of literature that
concerns decision making and emotion regulation is beyond the
scope of this paper. The focus therefore will be on functional neu-
roimaging and lesion studies involving humans, and emphasis will
be placed on specific sub-processes of decision making and emo-
tion regulation. Reversal learning refers to the capacity to alter
choice behaviour when the value of response options change. It
First, reversal learning is a process that can be easily constrained
and controlled in a laboratory setting. It is therefore easier to
interpret the functional contribution that distinct neural regions
make in this context relative to more complex decision making
investigations. Second, the relationship between decision making
deficits and emotion dysregulation have been most clearly artic-
ulated with respect to reversal learning, where efforts have been
made to link the two processes more formally [2,3]. With refer-
be the focus here: studies involving explicit attempts to modu-
late emotion (cognitive reappraisal and emotional suppression),
(emotional attention and inattention). In studies of emotional
reappraisal, participants are asked to intentionally modulate their
ically involves either reinterpreting the scene in less negative or
even positive terms (e.g., tears of joy rather than despair), or by
observer). In studies of emotional attention, the target process is
the impact of attentional manipulations on the representation of
emotional distracters at a neural and behavioural level.
There are three compelling reasons to consider decision making
and emotion regulation together. First, at a conceptual level, deci-
sion making and emotion regulation are linked by the pivotal role
that affect plays in each. Indeed, emotions have been succinctly
defined as “states elicited by rewards and punishers, that is, by
instrumental reinforcers” (p. 11) where rewards can be considered
something an organism will work to obtain, and punishers any-
thing an organism will work to avoid . Within this framework,
emotions play a pivotal role in decoding reward and punishment,
thereby driving systems devoted to action to attain optimal rein-
forcement. Accordingly, if behaviour is modulated by reinforcers,
and emotions are the principle means by which reinforcers are
assessed, top-down manipulations on emotion should have a pro-
this suggestion . Though the idea that abnormalities in emo-
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
has been well-developed , less consideration has been devoted
to the link between top-down control over emotion (i.e., emotion
regulation) and decision making.
A second reason to consider decision making and emotion reg-
ulation together is that coexisting abnormalities in these processes
are associated with aberrant social behaviours and psychiatric dis-
orders. For example, reversal learning deficits are associated with
reactive aggression , and a range of psychiatric disorders includ-
ing psychopathy [7,8], severe conduct disorder , frontotemporal
dementia , major depression , and bipolar disorder .
Although these disorders differ in several key dimensions, emotion
frustration intolerance, labile mood). One likely reason for the con-
vergence of decision making deficits and emotion dysregulation is
on largely overlapping neural regions.
ulation together are the potential benefits that can be conferred
upon our understanding of each. This is particularly true given that
the multi-faceted nature of emotion regulation means that studies
examining this complex phenomenon have limited functional res-
olution. For example, oftentimes participants are given freedom
in the particular regulatory strategy that they adopt during the
experiment. Even when task-instructions are constrained, it can
be difficult to determine whether the observed activity is related
to the target process (i.e., modulating an emotional response), or
non-target processes such as the emotional response itself, visual
or semantic processing of the emotion-inducing stimulus, retrieval
of the specific emotion regulation instructions, or other demands
on attention. One advantage to considering the function of neu-
ral regions in decision making tasks like reversal learning is that
which to interpret the data. Consequently, commonalities that are
evoked in each paradigm may be more readily interpretable.
in both decision making and emotion regulation are considered in
this review. These are ventrolateral prefrontal cortex (vlPFC; pre-
dominantly BA 47, and aspects of 11, 44 and 45), medial prefrontal
cortex (mPFC; including frontal pole, medial orbitofrontal cortex,
rostral anterior cingulate cortex and subgenual prefrontal cortex),
dorsolateral prefrontal cortex (dlPFC; lateral BA 8/9), and dorso-
medial prefrontal cortex (dmPFC; medial BA 8/9). The focus will
be in providing a brief overview of their anatomical connections,
followed by consideration of their functional role in both decision
making and affect regulation in turn.
2. Ventrolateral prefrontal cortex
2.1. Anatomical connections
The term “ventrolateral prefrontal cortex” (vlPFC) will be used
here to refer to the inferior caudolateral areas of frontal cortex
encompassing Brodmann’s Areas (BA) 47 and aspects of 11, 44
and 45 (see Fig. 1). Projections from neural regions supporting a
variety of sensory modalities converge in the vlPFC making it well-
in order to influence behaviour [13,14]. vlPFC receives extensive
input from temporal cortex both in its rostral and caudal extent as
well as superior and inferior divisions . Tracer studies involv-
between the vlPFC and amygdala exist, they are sparse relative
to other regions of prefrontal cortex [16,17]. Consequently, it has
been suggested that any role that vlPFC may play in regulating
amygdala output would likely involve indirect pathways through
Fig. 1. Location of regions of ventrolateral prefrontal cortex implicated in both
decision making and emotion regulation.
OFC or mPFC . The vlPFC is, however, connected with other
areas associated with emotion and action planning. It is important
to note the rich connections between the vlPFC and insular cor-
tex . The anterior insula, which is often jointly activated with
vlPFC during decision making and emotion regulation, is thought
to play a critical role in visceral integration, autonomic arousal, and
emotion [19–21]. Interactions between these two structures may
through its connections with premotor cortex  and basal gan-
making and emotional processes.
2.2. The role of vlPFC in decision making
(2) motor response inhibition; (3) stimulus-response reconfigura-
tion; and (4) attention to behaviourally significant stimuli. These
views are considered below in turn followed by a synthesis of how
they account for the data collectively.
2.2.1. Negative feedback encoding
A key component of effective decision making is the detection
of sub-optimal responding. Indeed, many models of faulty decision
making and behavioural dysregulation implicate insensitivity to
punishment as a crucial contributing factor[25–27]. Neuroimaging
studies suggest that vlPFC, or a region slightly anterior, represents
punishment during reversal learning [28,29]. In further support
of a punishment-processing perspective, vlPFC has been shown
to respond to primary reinforcers such as aversive tastes [30,31]
or smells . However, more recent conceptualizations specif-
ically tie vlPFC activity to punishment cues that are associated
with response change [33–35]. For example, using a probabilis-
tic reversal task, Cools and colleagues observed significant vlPFC
activity to errors that prompted response change on later trials,
but not to error feedback that did not prompt subsequent reversal.
Later reversal learning studies support the idea that vlPFC activity
does not reflect the level of punishment, but instead, is activated
neuroimaging study, Elliott and colleagues (2010) dissociated the
BOLD response to punishment from that associated with switch
cues, two processes that are conflated in basic reversal learning
studies. They demonstrated that both punishment and shift cues
activate the same area of vlPFC, implicating this region both in
behavioural control and reinforcer evaluation.
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
2.2.2. Motor response inhibition
One compelling conceptualization of vlPFC function is that it
plays a key role in action contexts that require the suppression
of previously rewarded responses . The strongest evidence
for response inhibition perspectives comes from studies involving
go/no-go or stop signal tasks. Go/no-go tasks involve serial pre-
sentations of stimuli (e.g., letters); participants respond when a
particular stimulus appears, and withhold responding to all other
stimuli. In these studies, robust vlPFC activity is associated with
no-go relative to go trials [39–42], particularly when a clear prepo-
tent response is established [39,40]. Whereas some studies suggest
a right-sided lateralization of this process [41,43], others implicate
bilateral involvement [40,42].
A second paradigm that supports response inhibition concep-
tualizations of vlPFC functioning is the stop-signal task. In these
a particular button and, on a subset of trials, this is followed by a
“stop-signal” (auditory cue) that indicates that the motor response
are impaired on this task; furthermore, the degree of impairment
is associated with the extent of the vlPFC damage . Data from a
combined fMRI and diffusion tensor imaging study implicate inter-
actions between vlPFC, basal ganglia, and pre-supplemental motor
area in response delay, stopping, or slowing [22,45]. Collectively,
these data provide strong evidence that vlPFC is activated when
demands are placed on response control, even in the absence of
punishment or aversive stimuli.
2.2.3. Stimulus-response reconfiguration
An alternate account of vlPFC function emphasizes the recon-
figuration of existing stimulus-response mappings. Accordingly,
rather than being specifically involved in punishment encoding or
pre-potent response inhibition, the suggestion is that vlPFC modu-
lates connections between stimulus representations and particular
motor responses when behaviour must change [36,37,46,47]. In
line with this conceptualization, we have found that activity in
vlPFC did not reflect changes in reinforcement value, but rather,
increased whenever a sub-optimal response was made, regard-
less of how disadvantageous the response . Further evidence
for this perspective came from a follow-up study that fractionated
inhibitory processes from overcoming avoidance during reversal
learning. We found that activity in vlPFC to suboptimal respond-
ing was similar across decision-contexts, whether the response
required participants to overcome their prior avoidance of a pre-
viously punishing stimulus, or to inhibit a previously rewarded
There is also recent evidence that vlPFC activity is modulated as
a function of social pressure for behavioural change. Thus, Finger
transgressions, regardless of whether observers were present (i.e.,
a situation in which behavioural change is warranted irrespective
of audience presence). In contrast, increased vlPFC activity to social
transgressions occurred only in the presence of an audience, when
the required social demands for behavioural change were in place.
In line with this, right vlPFC was shown to be activated while view-
ing higher relative to lower status social cues, suggesting that this
region might integrate hierarchy cues to guide appropriate social
behaviour . Together, these studies suggest not only that vlPFC
is involved in modulating behaviour, but that it may integrate con-
2.2.4. Attention to behaviourally significant stimuli
Activation of vlPFC is also observed during target detection
[51–53] and working memory task manipulations . A recent
study involving multiple working memory and response inhibi-
tion tasks indicate a conjunction of activity during these processes
within right vlPFC . In a modified Wisconsin card-sort task,
vlPFC was implicated during both attentional set shifting, and a
form of shifting similar to reversal learning . Hampshire and
Owen  have recently fractionated different forms of attentional
and response shifting using a multidimensional object discrimina-
tion task in which participants identified target stimuli amidst 4
options. They found that vlPFC activity was better accounted for
by shifting attention to different stimulus dimensions rather than
response switching. Additional evidence for this account comes
multiple decision contexts whether participants were inhibiting
responding to targets, generating a response to targets, or merely
counting target stimuli without making a specific response .
The results were interpreted as providing evidence that vlPFC is
recruited whenever task-relevant cues are detected.
2.2.5. Summary and implications
The data reviewed in the preceding sections are consistent with
the notion that vlPFC is implicated in altering behaviour when
the reward value of available response options change. However,
collectively, neither a punishment processing nor a response inhi-
bition conceptualization fully accounts for the empirical data. The
signal tasks indicating that vlPFC is crucially involved in inhibiting
or slowing motor responding to stop cues in the absence of punish-
ment information. A pure inhibition conceptualization, however,
does not account for findings that vlPFC is activated in other
contexts, such as when overcoming avoidance or attending to
target stimuli. Stimulus-response reconfiguration and attention
perspectives offer similar conceptualizations of vlPFC function and
provide reasonable accounts of the data reviewed here. Recon-
figuration accounts posit that vlPFC interacts with other regions
(e.g., basal ganglia and motor cortices) to modulate the current
vlPFC activity whenever competition between available response
accounts for activity observed in vlPFC to aversive olfactory and
gustatory stimuli. One possibility, however, is that such studies
activate a task-incompatible response (avoidance) that must then
be modulated (i.e., participants are in the unusual position of
tory stimuli). The attentional perspective emphasizes executive
response control by manipulating the salience of representations
associated with competing motor responses. However, it offers a
evant to the maintenance or execution of planned behaviour (e.g.,
related effects associated with vlPFC that are difficult to reconcile
with other perspectives. However, it does not necessarily predict
in conditions in which response change is required.
2.3. VLPFC in emotion regulation
The evolution of perspectives concerning the functional contri-
bution of vlPFC to emotion regulation bears a striking resemblance
to that of decision making. Thus, the role of vlPFC in emotion
regulation can be conceptualized along 4 main lines: (1) neg-
ative emotion encoding; (2) emotional response inhibition; (3)
emotional response modulation; and (4) attention to emotionally
2.3.1. Negative emotion encoding
Evidence that vlPFC is involved in encoding negative emotions
emotional stimuli without making explicit attempts to modulate
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
ness , and is correlated with the negative affect experienced
while viewing such films . Left vlPFC (BA 47) activity has been
associated with processing emotional images, particularly nega-
tive ones . Some studies have linked vlPFC activity to highly
arousing images regardless of whether they are positive or nega-
tive [61,62]. Others find laterality effects with right vlPFC (BA 47)
selectively responding to negative images, and left vlPFC (BA 47)
responding to both pleasant and unpleasant images . A con-
overlapping areas of vlPFC (BA 47) were activated when partici-
emotional stimuli . As in the decision making literature, there
is evidence that vlPFC detects or encodes emotional (particularly
negative) stimuli. However, as is reviewed in the following section,
making extends beyond reinforcement encoding.
2.3.2. Emotional response inhibition
Following some of the decision making literature reviewed
above, earlier conceptualizations of vlPFC function in emotion reg-
ulation emphasized inhibiting negative emotions. For example,
Ochsner et al.  found that greater right vlPFC (BA 47) was asso-
ciated with decreasing relative to increasing emotion. Similarly,
greater activity within an area of left vlPFC (BA 44) was observed
when participants attempted to “inhibit” sexual arousal to erotic
photos . In further support of an emotional suppression per-
spective, the suppression of negative emotion was associated with
greater activity in vlPFC (bilateral BA 46/10), and this activity was
inversely related to the subjective intensity of negative emotion
. Activity in left vlPFC (BA 44) was found to predict individual
differences in the capacity to suppress unwanted autobiographical
memories . Lastly, in a study examining the generation of dis-
cordant emotional expressions during movie clips, activity in right
to mimic the observed emotions .
Regions of vlPFC have also been implicated in the implicit reg-
ulation of emotions and attitudes. Thus, activity in right vlPFC (BA
47) was inversely associated with activity in the amygdala during
emotional expression labelling [69,70] or when viewing masked
angry facial expressions used as primes . Increased activity in a
similar region has been observed in response to unwanted explicit
associations , and when the effect of race on amygdala acti-
vation was attenuated . Lastly, studies of emotional attention
2.3.3. Emotional response modulation
attempts to reduce emotional responding; however, recent stud-
ies suggest a more flexible role for vlPFC in emotion regulation.
Paralleling the decision making literature, robust vlPFC activation
is associated with efforts to both decrease or increase emotional
responding through reappraisal [65,76,77]. Using a path model-
ing approach,  showed that the impact that right vlPFC has
on reappraisal success (reducing negative affect by providing a
positive interpretation of the stimulus) is mediated by interac-
tions with other structures. Specifically, two processes are engaged
by vlPFC, a negative appraisal process that involves the amyg-
dala, and a positive appraisal process that involves interactions
activity was associated with greater negative affect, and increased
nucleus accumbens activity was associated with reduced negative
Additional evidence of the flexibility of vlPFC function comes
review negative autobiographical memories while performing 3
distinct emotion modulation styles, one involving rumination,
another involving acceptance, and a third involving an objective
analysis of the emotions. The authors concluded that an area of
left vlPFC implements emotional appraisal operations regardless of
the regulatory strategy being employed. In another study, partici-
pants engaged in two regulatory techniques while watching video
clips . During the reappraisal condition, participants adopted
a detached perspective, focussing on the technical aspects of the
film. During the “suppression” condition, individuals were asked
to maintain a poker face, so that an observer would not be able
to detect what emotions were being subjectively experienced.
Although both techniques reduced subjective reports of negative
affect, only reappraisal, which was associated with earlier activa-
tion of vlPFC, dmPFC, and dlPFC, resulted in significantly reduced
2.3.4. Attention to emotionally significant stimuli
As has been noted, the vlPFC is considered a key node in
a network responsible for directing attention to unexpected or
otherwise salient stimuli that are outside the focus of attention
. One possibility is that vlPFC activity observed in emotion
regulation tasks involves vigilance for, or selective attention to,
aversive stimuli. For example, enhanced vlPFC activity has been
observed in anticipation of negative stimuli , and to negative
distracters that disrupt performance on an operant response task
ulating the distracting influence of emotional stimuli rather than
being involved in detecting these stimuli. Further evidence for a
regulatory role comes from studies examining how activity in this
region varies as a function of anxiety. Bishop et al. [82,83] have
found that left vlPFC activity to threat-related distracters is nega-
tively correlated with measures of anxiety, suggesting that vlPFC
played a role in regulating attention to threat-related distracters.
Similarly, Monk and colleagues report an inverse relationship
between anxiety and vlPFC activation during an emotional atten-
tion task in patients with anxiety disorders [75,84].
2.3.5. Summary and implications
The data reviewed in the preceding sections are consistent with
the notion that vlPFC plays a key role in modulating the impact
of stimuli on behaviour and subjective emotional states. As in the
decision making literature, the collective evidence from emotion
regulation studies does not support a negative representation or
augmenting or reducing subjective emotional states during cogni-
tive reappraisal; these functions may result from interactions with
dissociable neural regions, particularly the amygdala and ventral
striatum. In addition, activation occurs across a variety of emotion
this area makes a flexible contribution to modulating affect. It also
appears to play a role in regulating the impact of emotional dis-
tracters on operant behaviour, the efficacy of which is correlated
with questionnaire or clinical indices of anxiety.
2.4. Integrating vlPFC findings in decision making and emotion
tional contribution of vlPFC in the context of decision making and
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
very different, they consistently activate overlapping regions of
vlPFC (particularly BA 47), and similar explanations for this activity
have been offered in each research stream. Early theories empha-
sized a role for this region in encoding negative information or
inhibiting motor or emotional responses. Subsequently, however,
models of vlPFC function were revised to reflect a more flexible
contribution of this region. With regard to decision making, both
stimulus-response reconfiguration and attentional perspectives
provide reasonable accounts of the data. Reconfiguration perspec-
tives less clearly predict the finding that vlPFC activation occurs in
situations that do not require an overt motor response (e.g., during
counting); nevertheless, activity in this region appears particularly
robust when response modulation is required. The proposed con-
tribution of this region to emotion regulation differs between the
two perspectives. For example, an inverse relationship has been
noted in numerous studies between vlPFC activity and subjective
or physiological indices of anxiety. A response modulation expla-
nation emphasizes a role for vlPFC in modulating affect in this
context, which accounts for these data. Although less clear, atten-
tional accounts suggest a role for this area in directing attention to
less emotional or otherwise discordant representations. However,
The perspective favoured here is that vlPFC is involved in
modulating behavioural and emotional output given contextual
demands. For decision making, this would entail modulating
the relationship between stimuli and operant responses when it
becomes apparent that a given response is suboptimal (e.g., during
reversal learning), and when a pre-potent or tempting response
must be inhibited (e.g., during stop-signal tasks). For emotion reg-
ulation, this would be triggered whenever the natural emotional
feres with the target affective state. This occurs during cognitive
during emotional attention tasks (ignore the distracting emotional
stimuli). Although unconfirmed, the neuroanatomical data suggest
that the primary targets of this system in this regard are likely the
basal ganglia, amygdala, and anterior insula. Despite the conver-
literature, there remain important questions about vlPFC function.
ing this structure, the extent to which this region is necessary
for emotional or response change operations is unclear. It is also
unclear what the critical downstream targets of vlPFC are during
decision making and emotion regulation, and whether they differ
across these contexts.
3. Medial prefrontal cortex
3.1. Anatomical connections
In this section, the focus will be on ventral portions of medial
prefrontal cortex (mPFC), a term used here broadly to include the
frontal pole, medial orbitofrontal cortex (BA 10), and “perigenual
prefrontal cortex” (pgPFC) which includes subgenual prefrontal
cortex (sgPFC) and rostral anterior cingulate cortex (see Fig. 2).
Recent neural tracer studies have indicated that among all pre-
frontal areas, pgPFC have the densest connections with the
amygdala [16,17]. This area is unique not only in the number of
connections, but also in its organization; thus, Ghashghaei et al.
 show that pgPFC is the only area of prefrontal cortex to have
segregated input and output connections with the amygdala. In
contrast, only sparse and predominantly afferent connections exist
between rostral areas of mPFC (BA 10) and the amygdala . Con-
Fig. 2. Subdivisions of medial prefrontal cortex commonly implicated in decision
making and emotion regulation. Shown in red are medial aspects of frontal pole.
Ventromedial prefrontal cortex is shown in green. Perigenual prefrontal cortex
encompasses rostral anterior cingulate cortex (shown in blue) and subgenual pre-
frontal cortex (shown in yellow). (For interpretation of the color information in this
figure legend, the reader is referred to the web version of the article.)
amygdala than it receives . The mPFC exerts its influence over
amygdala output by way of excitatory connections with inhibitory
intercalated cells adjacent to the central nucleus of the amygdala
. In addition, these regions have connections with autonomic
centres in the hypothalamus and brainstem in turn, allowing for
influence over autonomic arousal . These connections allow for
both inhibitory or excitatory effects on affective processes through
interactions with the central nucleus of the amygdala as well as
the hypothalamus and brainstem . In addition, pgPFC has con-
nections with the ventral putamen, nucleus accumbens, and dorsal
caudate regions  as well as premotor areas . Regions of
mPFC are thought to influence mnemonic and semantic processes
through connections with superior temporal cortex [87,88] and
temporal pole , as well as perirhinal and parahippocampal cor-
tices . In short, the medial regions of prefrontal cortex have
rich connections with structures involved in processing reinforce-
ment, sensory input, semantic associations, memory, and motor
responding, placing it in an ideal position to modulate behaviour
and emotion to past and present encounters with affective infor-
3.2. The role of mPFC in decision making
Lesion data from human [3,91–93] and non-human  pri-
mates are consistent with suggestions that medial regions of
prefrontal cortex play a critical role in reversal learning. This func-
tional contribution has been conceptualized along 3 main lines: (1)
reward encoding; (2) expected outcome signalling; and (3) extinc-
tion and related processes. As will be reviewed below, there is
evidence that supports each perspective, and these different func-
tional conceptualizations may, to some extent, map onto distinct
subregions of mPFC.
3.2.1. Reward encoding
itates choice behaviour by flexibly encoding the reward value of
stimuli. Commonly, a functional division is made between medial
and lateral regions of prefrontal cortex, whereby mPFC is thought
to represent reward value for both abstract [28,34,95] and pri-
mary reinforcement [30,96–98]. In addition to this medial-lateral
divide, it has been proposed that whereas more anterior regions
of mPFC encode abstract reinforcement such as monetary reward,
posterior regions represent less complex reinforcements such as
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
smell or taste [99,100]. In addition, mPFC is activated by pleasant
visual scenes  and positive facial expressions . Although
the reward processing perspective is useful as a general rule
for medial and lateral prefrontal function, the empirical picture
appears more complex. For example, adjacent regions of mPFC
respond to both pleasant and unpleasant stimuli relative to neu-
tral stimuli [60,102,103]. Findings such as these have led to an
expansion of reward representation accounts.
3.2.2. Expected outcome signalling
Recently, the reward encoding position has been refined to
suggest that mPFC not only encodes reward, but is involved in
the representation of outcome expectancies [104,105]. There are
two key features to this model. One is the observation that neu-
rons within mPFC initially mark the reception of the reward
itself, but through learning, begin to respond to cues that predict
reward . Second, once learning occurs, the failure to obtain an
expected reward triggers a “prediction error signal” characterized
by a sharp decrease in neuronal activity . Evidence for this
position originally came from animal data indicating that mPFC
responds to cues that predict upcoming reward or punishment
[107,108]. Critically, mPFC also updates changes in the expected
value of stimuli, a key means by which it would support rever-
sal learning and other forms of decision making [109,110]. Data
from neuroimaging studies in humans are consistent with the idea
that activity in mPFC anticipates reinforcement value [111–113],
and delivers a prediction error signal when the expected value is
not received [36,112,114,115]. In a recent study, we dissociated
the BOLD response from the choice and feedback intervals of deci-
sion making. This revealed significantly less activity in mPFC (BA
10/32) during the choice phase of decision making when partici-
pants selected a novel stimulus (one where the outcome was less
clear) relative to when they selected a familiar stimulus (i.e., one
with a prediction error signal, we observed significantly reduced
activity in mPFC to error-feedback. Again, this reduction was par-
ticularly robust for stimuli that were previously associated with
reward (i.e., one for which the expected outcome was violated).
It has been noted that prediction error signalling may represent a
basic mode of brain function evident in multiple areas . The
area of human mPFC implicated in encoding expected outcomes
ranges from superior areas of medial prefrontal cortex (BA 10/24;
), lateral frontal pole (BA 11; ), medial frontal pole (BA
10; [115,116]), and rostral anterior cingulate cortex (BA 10/32;
). Another region consistently implicated in expected out-
come encoding and prediction error signalling is ventral striatum
[117–119], though the contribution made by this region may differ
both regions contribute to expected value encoding, mPFC activity
particularly reflects the probability of reinforcement [111,120].
3.2.3. Extinction and related processes
sion making and emotion regulation dates back to earlier work in
rodents involving the extinction of a fear conditioned response.
Extinction is the decrease in fearful responding that normally
occurs when a fear conditioned stimulus (CS) is repeatedly pre-
sented in the absence of an aversive unconditioned stimulus (US).
(infralimbic Area 25 and PL 32) left fear conditioning intact, but
resulted in impaired extinction . More recent work indicates
that important functional subdivisions exist within rodent mPFC
with regard to extinction; whereas infralimbic cortex stimula-
tion reduces fear conditioned responding, activation of prelimbic
cortex augments a fear conditioned response . On the basis
of these and other findings, Peters et al.  have proposed
that distinct regions of mPFC modulate appetitive and aversive
conditioning through alternate pathways. Specifically, prelimbic
cortex increases appetitive responses through excitatory connec-
tions with the core of the nucleus accumbens, and fear-related
responses through excitatory connections with basal areas of the
amygdala. In contrast, infralimbic areas are thought to reduce
appetitive responses through interactions with the shell of the
nucleus accumbens, and decrease fear-related behaviour by acti-
vating inhibitory intercalated amygdala neurons.
Later work has suggested that mPFC is particularly important
for the consolidation and recall of extinction learning [124,125].
According to this view, extinction does not completely erase an
initial CS-US association, but is thought to form a new memory,
which competes with prior fear conditioned stimuli for control of
behaviour. Recent data suggest that the initial fear memory can be
further degraded or perhaps erased through the use of a retrieval
cue to prompt reconsolidation [126,127]. It is important to note
however that vmPFC appears to be involved not only in extinction
memory, but perhaps also in the expression of extinction; thus,
microstimulation of infralimbic cortex has been shown to reduce
freezing to a fear-conditioned tone that had not yet been subjected
to extinction .
The subgenual cingulate cortex is thought to be the human
homologue of the rat infralimbic cortex [13,129,130]. In contrast,
dorsal anterior cingulate areas are thought to be functionally
analogous to rat prelimbic cortex . Mirroring work done
in rodents, neuroimaging studies involving humans implicate
subgenual regions of prefrontal cortex in extinction [132–134],
and dorsal regions of cingulate cortex in fear expression .
However, the human neuroimaging data also implicate a more
genual prefrontal cortex . Indeed, areas including the frontal
guishing approach and avoidant operant responses during passive
avoidance learning .
3.2.4. Summary and implications
There is clear evidence that mPFC flexibly encodes the value
of stimuli; however, a pure reward-encoding conceptualization of
mPFC is not sufficient to account for the data gleaned from the
reversal learning literature. Emerging data has resulted in an elab-
orated position suggesting that mPFC encodes expected outcomes
(positive and negative), and signals when the expected reinforce-
ment is not obtained. This model reflects the variety of results
associated with mPFC function including reward representation,
anticipatory encoding of outcomes, prediction error signalling,
and reversal learning. A second function accorded to mPFC is the
extinction of conditioned responses through interactions with the
amygdala. In rodents, the regions that are emphasized in each pro-
cess appear dissociable; whereas rostral areas of mPFC are more
often implicated in encoding outcome expectations , poste-
rior infralimbic areas of mPFC are considered crucial for extinction
. The extent to which these two functions are governed by
separate regions of mPFC in humans is unclear. Neuroimaging
studies have implicated anterior and posterior regions of mPFC in
both processes. One possible explanation concerns the apparent
differences in how reinforcement is represented in human pre-
frontal cortex along a rostral and caudal division (e.g., ). For
example, whereas extinction studies that involve abstract rein-
forcement might implicate more rostral areas of prefrontal cortex
(e.g., [48,136]), those studies that utilize primary reinforcement
may implicate more posterior regions of prefrontal cortex (e.g.,
). Another possibility, discussed below, is that extinction rep-
resents a subcomponent of outcome expectancy and prediction
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
3.3. The role of mPFC in emotion regulation
Medial regions of prefrontal cortex figure prominently in many
role of mPFC in human emotion regulation were originally derived
from rodent work concerning the extinction of conditioned asso-
ciations. However, there have been some recent departures from
these models, and overall, there is less specificity and agreement
regarding the functional role of mPFC in emotion regulation. Two
main perspectives of mPFC relevant to emotion regulation will
be reviewed in the following sections: (1) emotional modulation
(extinction, reflection and augmentation); and (2) expected outcome
3.3.1. Emotional modulation: extinction, reflection and
Emotion regulation research often adopts the extinction per-
in regulating negative affect. Initially, this translation appeared
most relevant for anxiety disorders such as post-traumatic stress
disorder, in which a core feature is an exaggerated physiological
response to cues that no longer signal threat. However, this per-
spective has been extended to include more complex forms of
human emotion regulation . According to this view, mPFC
plays a critical role not only in regulating affect by changing
conditioned associations that are no longer relevant, but also by
facilitating the voluntary regulation of emotional responses to
conditioned or unconditioned stimuli (e.g., during cognitive reap-
praisal). It is also thought to play a role in regulating complex
occurs in a major depressive episode). Support for this perspective
chiatric disorders, reappraisal paradigms, and emotional attention
With regard to psychiatric disorders, mPFC dysfunction is
linked to a range of pathologies featuring emotional dysregula-
tion including mood disorder [138,139], psychopathy , and
borderline personality disorder . According to the extinction
perspective, pathological emotional dysregulation can result from
a failure of mPFC to effectively modulate the expression of neg-
ative and positive conditioned associations in the amygdala and
nucleus accumbens respectively . Data from studies exam-
ining reappraisal and other forms of explicit emotion regulation
also implicate mPFC. For example, activation in subgenual PFC has
been linked with decreasing negative emotion using an objective,
detached perspective [65,76]. Increased activity in subgenual and
 and reappraisal success . In a study that intersects both
extinction learning and cognitive reappraisal, Delgado et al. 
asked participants to regulate their emotional response to stimuli
to regulate their emotional response to fear-conditioned stimuli
through reappraisal, increased activity in mPFC was observed; fur-
thermore, ventral areas of mPFC (BA 32) that responded during
regulation overlapped with the same area of mPFC activated dur-
ing classic extinction (i.e., one without a reappraisal component;
Although less commonly implicated than dorsal regions of
prefrontal cortex, support for a modulatory role of mPFC dur-
ing emotional attention tasks also exists. In these experiments
emotional distracters (e.g., emotional facial expressions or scenes)
compete with target task-related stimuli for representation and
control over behaviour. In some studies, the rostral ACC has been
implicated in resolving emotional conflict through interactions
with the amygdala . In a recent study of emotional atten-
tion , we asked participants to identify a target fearful or
happy facial expression that was surrounded by either congru-
ent, incongruent, or neutral facial expressions. When faced with an
incongruent expression, participants showed enhanced functional
coupling between mPFC (BA 10) and the amygdala; furthermore,
the level of coupling was correlated with behavioural indices of
response conflict during emotionally incongruent presentations.
There is also evidence that mPFC resolves conflict not only at the
level of neural “representation,” but may also determine whether
an emotional stimulus reaches consciousness. We have recently
used fMRI and binocular rivalry to delineate the neural correlates
of emotional awareness during presentations of discordant facial
perceived, and increased connectivity with perigenual prefrontal
cortex (pgPFC; BA 32/10) when fear was present, but suppressed
from awareness. These findings raise the possibility that interac-
tions between pgPFC and the amygdala, previously implicated in
extinction, may also influence whether or not an emotional stimu-
lus is accessible to awareness.
The majority of emotion regulation studies have focused on the
the effects of augmenting versus reducing an emotional response.
As a consequence, the extent to which mPFC effects are specific to
emotional suppression is unclear. The data from neuronal tracer
 and rodent studies of extinction  are consistent with the
idea that mPFC can both increase and decrease positive and nega-
tive emotion. The idea that mPFC is involved in both reducing and
that increased mPFC activity is sometimes observed in condi-
tions that involve greater emotional representation. For example,
greater activity in mPFC has sometimes been observed during the
attend relative to regulate conditions of a reappraisal task .
More recently, conjunction analysis of the two processes pro-
vide some evidence that similar regions of supragenual mPFC are
engaged whilst augmenting or decreasing an emotional response
. Lastly, when 3 distinct styles of emotional responding were
compared, regions of sgPFC and other mPFC regions showed the
ing the greatest emotional arousal), and decreased parametrically
with the use of the intermediate and most effective strategies .
These findings are interpreted as evidence that sgPFC is involved
in representing negative emotional states or negative properties of
For example, mPFC at rest is correlated with subjective ratings of
negative affect  and increased activation of sgPFC is associ-
ated with sad mood induction [147,148]. Conversely, reductions in
sgPFC activity have been associated with recovery from mood and
anxiety disorders , and damage to mPFC is associated with
reduced risk for major depression . It has been proposed that
regions of vmPFC may confer depressive symptoms either by play-
ing a role in the generation of negative emotion, or by supporting
self-awareness and therefore depressive rumination . Inter-
estingly, stimulation of sgPFC has been introduced as a treatment
tures associated with emotional states. It is interesting to note that
in animal studies, stimulation of sgPFC reduces emotional output
from the amygdala through activation of inhibitory inter-neurons
3.3.2. Expected outcome signalling
An alternate conceptualization of the functional role of mPFC
to emotion regulation makes explicit links with the reversal learn-
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
ing literature. Blair [2,155] has suggested that an additional means
by which mPFC supports emotion regulation is through its role
in encoding realistic outcome expectancies. This formulation rests
on two key observations. First, abnormal performance on tasks
thought to be sensitive to outcome expectancy formation has
been observed in a number of conditions that feature increased
risk for reactive aggression including bipolar disorder , psy-
chopathy , severe conduct disorder , intermittent explosive
disorder , and orbitofrontal cortex injuries [3,157]. Second, it
is thought that frustration, a key precursor to reactive aggression,
is elicited by a failure to obtain a desired goal . Accordingly,
impaired ability to form realistic outcome expectancies may lead
to poor decisions, increased frustration, and greater risk for reac-
tive aggression [155,159]. In support of this explanation, recent
disorder and abnormal prediction error signalling . Although
this view does not exclude a key role for mPFC in modulating or
representing emotion, it suggests an additional indirect role for
this region in modulating frustration, and therefore in emotion
3.3.3. Summary and implications
The data clearly indicate a role for mPFC in modulating prior
conditioned associations. Moreover, there is evidence to suggest
that this region plays a role in both approach and avoidance learn-
ing. However, the functional role for this region in more complex
forms of human emotion regulation remains unclear. The animal
data that originally formed the basis for implicating mPFC in this
context are not consistent with some of the data and theories
derived from studies of human emotion regulation. For example,
the animal literature emphasizes a role for mPFC in the consol-
idation, retention, and expression of extinction memory. Yet in
humans, overlapping areas of mPFC have been associated with
extinguishing or modulating emotion, but also with augmenting
emotion and pathological emotional states. One possible reason
for this discrepancy is the existence of cross-species differences
in the function of this region. For example, it has been suggested
that some aspects of the extinction model derived from animals
may not translate well to humans, where conditioning is thought
to involve additional higher-order cognitive elaborative processes
. A second possibility is that several neurochemically or
anatomically distinct sub-processes are at work within human
prefrontal cortex that can have opposing effects, and which may
make different contributions in different behavioural contexts. It is
of fear (e.g., startle versus freezing) may rely on distinct regions
of vmPFC . A third possibility is that the increased activity
associated with emotional induction or pathological mood states
may reflect frustrated attempts to regulate emotional responding
rather than emotion representation or generation. According to
sgPFC activity due to a functional disconnection with subcortical
3.4. Integrating mPFC findings in decision making and emotion
Clear similarities exist concerning the functional contributions
lent evidence that mPFC is involved in representing outcomes and
in extinguishing conditioned associations. The data indicate that
processes attributed to mPFC include the modulation of both emo-
tion and behaviour. It is also apparent from the data reviewed
that considerable heterogeneity of function exists within this area.
in reward value during decision making; it is also associated with
increases or decreases in levels of affect during emotion regulation.
a variety of functions ascribed to mPFC. For example, the find-
ings supporting reward encoding are predicted by the formulation
that mPFC signals the expected value of stimuli or the anticipa-
tion of reward. In addition, extinction-related activity in mPFC,
which occurs when a conditioned stimulus is presented without
reinforcement, can be conceptualized as a prediction error signal
that facilitates updating the value of the new stimulus. Although
less clear, emotional augmentation seen in some studies may also
be driven to some extent by expected value encoding or predic-
tion errors (e.g., these studies often present threat-related stimuli,
such as fearful faces in the absence of environmental threat). Nev-
ertheless, the relationship between structure and these apparently
complementary processes remains unclear. There are also remain-
ing questions concerning the function of this region in decision
plex forms of emotion regulation, such as cognitive reappraisal,
or is it involved only when a conditioned stimulus no longer pre-
dicts an established outcome? Do the pathways associated with
mPFC change according to whether the objective is to increase
or decrease an emotional response? Lastly, the mPFC has connec-
tions with temporal cortical structures involved in memory and
semantic associations, yet much less is known about how these
pathways operate in the context of decision making and emotion
4. Dorsomedial and dorsolateral prefrontal cortex
4.1. Anatomical connections
In this section, the term dorsolateral prefrontal cortex (dlPFC)
will be used to refer to lateral regions of BA 8, 9, and superior areas
of 46. Dorsomedial prefrontal cortex (dmPFC) will refer to poste-
rior medial regions of prefrontal cortex located primarily above the
cingulate gyrus (BA 8/9). Fig. 3 shows the location of dlPFC and
dmPFC as they are defined here. Anterior regions of primate dlPFC
(BA 46/9) have rich connections with multiple areas in temporal
cortex including superior temporal areas, rostral temporal cortex,
and the retrosplenial cortex [162,163]. Connections between dlPFC
and superior regions of temporal cortex are thought to facilitate
both inhibitory and excitatory control over the strength of stimu-
(BA 9/46) and lateral and medial regions of parietal cortex, though
these connections are absent in more dorsal regions (BA 9; ).
Mid-dlPFC is also unique in that it sends efferent fibres to retro-
splenial cortex (BA 29 and 30), perhaps enabling this region to
influence working memory . Although lacking in connections
with retrosplenial areas, posterior dlPFC (BA 8) has connections
with posterior visual temporal areas, and early visual cortex (V2;
). Posterior regions of dlPFC (BA 8) are also noted for having
Posterior dlPFC and dlPFC have few if any projections to the amyg-
dala , suggesting that any major role that these regions might
with other structures. Although dorsal cingulate regions (dorsal
area 24) have dense projections to the amygdala, connections with
. The areas of dmPFC located above the cingulate gyrus (BA 8)
will be the focus of this section, as they are most often activated
during reversal learning [33,36,37] and emotion regulation .
With its connections to areas involved in multimodal sensory rep-
resentation, visuospatial processes, and memory, dorsal regions
of prefrontal cortex are well-positioned to select and prioritize
relevant stimulus features and memories to guide goal-directed
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
Fig. 3. Areas of dorsal prefrontal cortex frequently associated with decision making
and emotion regulation include (a) dorsomedial prefrontal cortex and (b) dorsolat-
eral prefrontal cortex.
4.2. The role of dorsal prefrontal cortex in decision making
Until recently, dorsal regions of prefrontal cortex were thought
a double dissociation has been noted in non-human primate stud-
ies whereby lesions of orbitofrontal but not dorsolateral regions
of prefrontal cortex cause reversal learning deficits, and lesions to
dorsolateral but not orbital prefrontal cortex disrupt attentional
set shifting [92,94]. It is important to note that although lesions
to dorsal prefrontal cortex leave reversal learning intact, they do
disrupt more complex (but related) forms of reward-related deci-
sion making such as risk aversion learning [167,168]. Furthermore,
neuroimaging studies consistently implicate dmPFC and dlPFC in
reversal learning [29,33,36–38]. Together, these studies suggest
not only that these areas are involved in reward-related decision
making, but that their contribution might be essential under some
circumstances. Two main perspectives concerning the functional
ing each will be described: (1) resolving decision conflict through
attention; (2) reinforcement encoding accounts.
4.2.1. Resolving decision conflict through attention
One possibility is that dorsal prefrontal regions facilitate deci-
sion making through attentional processes [37,169]. According to
influential conflict monitoring models of attention, dmPFC signals
instances of increased response conflict, triggering dlPFC to enact
compensatory adjustments in cognitive control [170–172]. Subse-
quent studies have supported the view that cognitive control is
achieved by amplifying cortical responses to task-relevant repre-
sentations in sensory cortices . It has been suggested that in
the context of decision conflict, dlPFC augments the representa-
tion of relevant stimulus and reinforcement information to guide
choice behaviour. “Decision conflict” refers to the level of indeci-
sion; it can be defined as the extent to which a particular response
is primed by the current response-related stimuli or reinforcement
. Decision conflict therefore reflects the degree of ambiguity
that exists concerning the current values of the response options,
and therefore the current optimal response. Accordingly, increased
decision conflict is expected during exposure to novel contingen-
cies, changes in reinforcement, or changes in the number of viable
responses. Data from neuroimaging studies support this concep-
tualization of function. Enhanced dmPFC and dlPFC is observed
errors [36,38], or when adapting to changes in stimulus-response
values . In addition, increased activity in dorsal regions of pre-
frontal cortex have been observed when participants must choose
between two similarly valued objects [37,169,174] or with para-
metric increases in the number of viable response options . It
has recently been shown that the same regions of dlPFC and dmPFC
that are modulated by reversal errors, are also activated to deci-
sion conflict generated by choosing (correctly) between similarly
valued objects . In a recent fMRI study , we examined sub-
processes of reversal learning, revealing an interaction between
decision conflict elicited the greatest dlPFC activity. Furthermore,
the condition associated with the greatest dlPFC activity in early
trials elicited the least activity in later trials. We have suggested
that dlPFC activity during periods of high decision conflict not only
facilitates the resolution of conflict during early encounters of new
stimulus-response values, but that it does so in a manner that may
formance on later trials. Thus, activity in dlPFC may have an impact
on both current and future regulatory concerns.
4.2.2. Reinforcement encoding accounts
The reinforcement-related accounts of dorsal prefrontal cor-
tex function concern dmPFC, rather than dlPFC, and emphasize
either error processing or reinforcement tracking. With regard to
the former, dmPFC has been implicated in processing losses ,
processing errors [177,178], or signalling contexts in which the
likelihood of errors is increased . Although this account is
supported by neuroimaging studies (reviewed above) that show
increased error-related activity in this region, it is not consistent
with observations of enhanced activity in this area in the absence
of errors or losses. More recently, reinforcement history tracking
accounts of dmPFC function suggest a more direct role for this
region in encoding reward-related information in the context of
decision making. The majority of the results come from animal
studies of reversal learning and related paradigms. For example,
it has been suggested that dmPFC integrates historical information
about actions and outcomes (both rewarded and non-rewarded)
over time to guide responding when reward-contingencies are
ambiguous [180–182]. Similarly, dmPFC has been implicated in
assessing the relative cost and benefit of performing an action for
reward [183,184]. In a revealing study, Kennerley and colleagues
 report that whereas monkeys with dmPFC lesions were
to adjust responding following errors. The authors examined the
influence of previous outcomes on subsequent choices and found
was significantly lower. In a probabilistic setting, controls reached
optimal performance after receiving 2–3 consecutive rewards for
making the correct response (i.e., they appeared to make use of
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
In contrast, macaques with lesions to dmPFC were unable to cap-
italize on knowledge concerning the history of reinforcement to
maintain reward-related responding.
The evidence reviewed in this section supports the idea that
dorsal regions of prefrontal cortex play an important and some-
times critical role in reward-related decision making. The decision
conflict perspective provides an integrated account for both dor-
somedial and dorsolateral PFC that accords with the attention
literature, and explains the specific pattern of findings concern-
ing the role of dorsal prefrontal cortex in decision making. In
contrast, reinforcement related accounts explain only the involve-
ment of dmPFC and diverge from current dominant models of
attention. The error processing perspectives of dmPFC function
appear overly constrained, failing to account for why activity in
this region is modulated by correct responses. Both the decision
conflict and reinforcement history perspectives explain why con-
tributions from dorsal prefrontal cortex are unimportant when
response options are categorically correct or incorrect, but become
critical in more complex decision making contexts where rein-
for how contingency ambiguity is resolved differs between these
two perspectives. According to the decision conflict perspective
favoured here, similar dorsal regions of prefrontal cortex resolve
conflict whether it is perceptual conflict driven by conflicting stim-
ulus features [170,172,185], or decision conflict driven by having
to choose between ambiguously valued objects or an increasing
may involve: (1) increasing the salience of objects that predict
optimal reward; (2) inhibiting the representation of suboptimal
stimuli; and (3) increasing the salience of reinforcement informa-
tion to support learning. According to the reinforcement history
tracking perspectives, activity in dmPFC should be modulated as
the importance or complexity of the reinforcement history of the
available responses increases. This would conceivably occur when
more response options are being deliberated upon or when rein-
forcement is probabilistically determined. Because both decision
conflict and reinforcement history tracking perspectives are pred-
icated on the salience of contingencies, it is difficult to dissociate
these processes experimentally. One of the advantages of the deci-
activity coincides with dmPFC. Furthermore, because it coincides
with functional explanations of the contributions of these regions
in other contexts (e.g., the Stroop task), it provides a parsimonious
model of dorsal prefrontal cortex function. It is important to note,
however, that the two accounts need not be mutually exclusive.
For example, dmPFC may have access to past information which it
4.3. The role of dorsal prefrontal cortex in emotion regulation
As with decision making, emphasis for emotion regulation was
originally placed on ventral regions of prefrontal cortex. Yet more
recently, data indicate a potential role for dorsal prefrontal cor-
tex in emotion regulation. Both dlPFC and dmPFC are consistently
activated in studies of explicit emotion regulation [59,64,65,186];
activity in these regions have been correlated with biological or
behavioural indices of regulation success [64,67,132,145]. Fur-
thermore, it was recently shown that lesions to bilateral dorsal
major depression . In this section, two main functional per-
spectives concerning the contribution of dorsal prefrontal cortex
to emotion regulation will be described: (1) resolving emotional
conflict through attention; (2) reappraisal strategy generation or
4.3.1. Resolving emotional conflict through attention
Due to the complex nature of cognitive reappraisal paradigms,
it can be difficult to delineate the functional contribution of dor-
sal prefrontal cortex to human emotion regulation. However, it is
noteworthy that studies of emotional attention, which can offer
a more constrained experimental environment, have found an
inverse relationship between activity in dorsal prefrontal cortex,
and activity in emotion-related brain areas, particularly the amyg-
dala [74,187,188]. The constrained nature of these tasks lends
itself well to interpreting the role of dorsal prefrontal cortex in
this context, which most commonly involves reference to biased
competition models of attention . The model explains the
observation that when multiple stimuli are presented in the visual
field, they elicit less activity than when the most effective stimulus
for that neuron is presented in isolation. Thus, multiple stimuli are
not processed additively; instead, they are processed in a mutu-
ally inhibitory fashion whereby a gain in neural activity for one
object occurs at the expense of activity for another. This competi-
tion for neural representation and control over behaviour is biased
by bottom-up sensory-driven mechanisms (e.g., visual salience),
and top-down influences generated outside of sensory cortices
(e.g., executive attention; ). Emotion is also thought to be a
bottom-up modulator of stimulus representation, giving valenced
information enhanced access to processing resources [190,191].
in the visual system at the neuronal level , and at the systems
level using fMRI . The top-down control system is thought
to consist of dorsal prefrontal cortex, whereby dmPFC signals
instances of response conflict, triggering compensatory adjust-
ments in cognitive control via dlPFC [170–172]. In accordance with
this model, studies show that emotion-related amygdala activity
is significantly reduced when attentional resources are sufficiently
engaged elsewhere [83,188,194,195].
Although most evident within the confines of an emotional
attention task, this specific mechanism likely plays a more gen-
eral role in emotion regulation. The suggestion here is that the
role played by dorsal prefrontal cortex in the context of emotional
attention and in cognitive reappraisal paradigms is the same. In the
course of emotion regulation tasks, participants are asked to adopt
a different perspective, or to reinterpret the emotions, actions or
outcomes depicted in visual stimuli. To achieve this requires the
activation of alternative representations in temporal cortex. These
alternate representations can be different objects in the stimulus
itself, or probably more commonly, other endogenous represen-
tations (i.e., memories or semantic associations that are related,
but emotionally discordant with the stimulus). When these alter-
native representations are activated, they would compete with,
and inhibit, the original negative emotional responses activated by
the stimulus. Although speculative, this particular account unifies
the common findings concerning the relationship between dorsal
prefrontal cortex activity and emotional responding in studies of
cognitive reappraisal and emotional attention.
4.3.2. Reappraisal strategy generation or maintenance
An alternate conceptualization of dorsal prefrontal cortex func-
tion concerns the construction or maintenance of reappraisal
strategies [65,132,145]. This view differs from attentional accounts
in that it adopts a working memory perspective whereby dor-
sal prefrontal cortex is responsible for holding information online
needed to generate the regulatory strategy (e.g., adopt a clini-
cal perspective or fictionalize the image). According to this view,
increased activity in dlPFC would be associated with enhanced
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
related with biological or behavioural indices of negative emotion,
as has been shown in a number of studies [64,67,132,145]. It is
less clear from this perspective what happens on a neural level to
actually transform the emotional response following the represen-
tation of strategic regulatory information. One suggestion is that
prefrontal cortex is involved in altering the “the emotional mean-
ing of the stimuli,” and thereby reduces affective responding .
A second possibility, proposed by Delgado and colleagues ,
is that once lateral PFC regions manipulate information related to
emotion regulation strategies online, they exert a regulatory influ-
ence over the amygdala by way of mPFC. The subsequent exchange
between mPFC and the amygdala is thought to be the same as that
observed when extinguishing a conditioned association.
4.3.3. Summary and implications
Both attentional and working memory perspectives account
well for the apparent involvement of dorsal prefrontal cortex in
empirically in the context of reappraisal tasks. A key difference
in the nature of these two accounts is how dlPFC interacts with
other structures to regulate affect. For example, according to atten-
tional accounts, the processes initiated by dorsal prefrontal cortex
in the context of emotional attention tasks is no different from
that observed in cognitive reappraisal tasks. That is, interactions
between dlPFC and temporal cortices are critical for modulating
the strength of stimulus representations that compete with one
another during emotion regulation. According to this perspective,
no interaction between dlPFC and mPFC is necessary to regulate
affect. Instead, the activation of healthier representations by dlPFC
will compete in temporal cortex with negative representations
engendered by the stimulus, indirectly modulating output of sub-
cortical regions. This perspective differs from working memory
accounts, which implicate dlPFC in holding strategic regulatory
information online in order to modulate the emotional response.
According to this latter position, emotion regulation is thought to
be ultimately enacted by modulatory connections between mPFC
4.4. Integrating dorsal prefrontal cortex findings in decision
making and emotion regulation
Overlapping areas of dorsal prefrontal cortex have been
implicated in both emotion regulation and decision making. Cur-
rent functional conceptualizations of dorsal prefrontal cortex
memory, or attention. However, only the attention-based account
PFC are activated in ambiguous decision making contexts, when
voluntarily modulating a natural emotional response, and when
It should be noted that there is some functional heterogeneity
within dorsomedial regions of prefrontal cortex. For example, the
label “dorsal ACC” has often been used more broadly when refer-
to the cingulate gyrus in studies of perceptual conflict  and in
studies of emotion regulation . The term dmPFC is used here
instead to refer to the regions that lie predominantly above the
cingulate gyrus (BA 8/9). It should be noted that although activity
in dorsal cingulate cortex proper (BA 24) has been correlated with
emotional reappraisal success , it is also frequently associated
with the generation of negative affect . Indeed, surgical abla-
tions of dorsal ACC have been used to control intractable mood and
anxiety disorders . As mentioned earlier, human dorsal ACC is
thought to be functionally analogous to rat prelimbic cortex, which
is associated with the expression of fear conditioned responding
. It is possible that functional heterogeneity within this dor-
sal region of medial prefrontal cortex exists whereby more ventral
areas are associated with negative affect, and more dorsal regions
with conflict monitoring.
There are several areas that require further study to elucidate
the nature of the contribution from these regions. For example,
during decision making, are dorsal regions of prefrontal cortex
involved in increasing the salience of conditioned stimuli, rein-
forcement contingencies, or reward history? Is there a functional
decisional and emotional conflict while dlPFC exerts attentional
control as has been suggested in studies of perceptual conflict?
What are the consequences to emotion regulation of focal lesions
to dorsomedial versus dorsolateral PFC?
5. General conclusions
In this review, a description of the prevailing theoretical per-
spectives concerning the functional contribution of vlPFC, mPFC,
and dorsal prefrontal cortex to decision making and emotion reg-
ulation were described, and evidence for each discussed. The data
are consistent with suggestions that common functional computa-
tions underlie adaptive decision making and emotion regulation;
furthermore, these computations are likely governed by overlap-
ping areas of prefrontal cortex. Collectively, the evidence suggests
that two partially dissociable systems within prefrontal cortex are
mPFC, and a dorsal system involving dmPFC and dlPFC. An informal
theoretical model is shown in Fig. 4 that provides an overarching
framework concerning how these systems may interact with other
neural regions to govern decision making and emotion regulation.
According to the model, vlPFC is activated whenever a designated
action or emotional response must be modulated to satisfy current
contextual demands. This activity is associated with behavioural
control “online” (i.e., as it is encountered in real time), as evidenced
tion, vlPFC input has the impact of modulating the probability of a
particular response in future encounters with the stimulus, as is
evidenced by the fact that greater vlPFC activity to error-feedback
is associated with response change on future trials. In the context
of decision making, this may involve projections from vlPFC to dor-
sal striatum where basic stimulus-response maps are represented
of vlPFC in emotion regulation differs from mPFC; whereas vlPFC
is involved in modulating the existing (i.e., activated) response to
an emotional stimulus in order to achieve a target action or emo-
expected outcome of a stimulus when the affective significance of
uation). In addition, vlPFC may also receive inputs from mPFC that
subsequently impact decision making and emotion regulation. For
example, mPFC may relay information about changes in expected
outcome to vlPFC, where changes in behavioural and emotional
output are facilitated . However, the influence of expected out-
come information on vlPFC is likely limited. For example, activity
in vlPFC is not modulated by changes in expected outcome that are
not sufficient to warrant behavioural change . Furthermore, it
has been noted that intact vlPFC function during decision making
can exist even in the presence of abnormalities in prediction error
signalling in mPFC [114,155]. An alternate possibility is that input
change ; however, this possibility requires further empirical
The role of mPFC in decision making and emotion regulation
is complex and multi-faceted. However, projections originating
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
Fig. 4. A hypothetical model indicating areas of overlap in neural pathways implicated in regulating decisions and emotions. Lines indicate primary pathways by which
neural regions are thought to influence decision making and/or emotion regulation. Hashed lines indicate pathways that likely influence either process, but for which less
making) trigger mPFC to update stimulus-reinforcement associations through input to the amygdala (a) and nucleus accumbens (b), thereby modulating output in these
regions. Through interactions with amygdala and nACC, distinct subdivisions of mPFC are thought to be capable of increasing or decreasing fear-related and approach-related
responses. Information about changes in expected outcome may also be relayed from mPFC to vlPFC (c). When a new response is required during decision making, input
from vlPFC to dorsal striatum alters the response evoked by a particular stimulus (d). In addition, vlPFC may alter both decisions and emotions by modulating activity in nACC
(e), temporal cortex (f), anterior insula (not shown), and potentially via sparse projections to the amygdala (g). Through a dorsal pathway, dmPFC, is activated by response
conflict and has access to past reinforcement information, relaying this information to dlPFC where selective attention processes are implemented (h). Subsequently, dlPFC
modulating activity within amygdala (j) and possibly mPFC (k). Contributions from dACC (BA 24) have been implicated in amplifying emotional responses, possibly through
inputs to the amygdala (l). Inputs from the amygdala to nACC (m) are thought to modulate approach behaviours. Arrows indicate the hypothesized primary direction of
influence in this context, but are not representative of all projections.
from distinct regions of mPFC that target the amygdala and ventral
striatum are likely important for signalling expected outcomes of
actions, and for modulating associations formed in these regions
when violations in expected outcomes occur [104,105]. With
regard to decision making, these processes allow organisms to
learn the value of actions, and encode any changes that occur
to the value of these options. On the basis of the reversal learn-
ing literature, behavioural change may be facilitated when this
reinforcement change information is relayed to other structures,
including the amygdala, ventral striatum, and vlPFC. One possibil-
ity is that the role of mPFC in emotion regulation can be considered
an extension of expected outcome encoding and prediction error
signalling evident during decision making. For example, extinction
involves interactions between mPFC and amygdala, which modu-
late stimulus-reinforcement associations when they are no longer
appropriate [123,198]. This process is triggered when conditioned
stimuli are presented in the absence of the predicted outcome (i.e.,
a prediction error signal). In addition, intact outcome expectancy
signalling mediated by mPFC is thought to indirectly support the
regulation of aggression by reducing the incidence of frustrative
non-reward [155,159]. As noted above, information from mPFC
concerning violations in expected reinforcement may be relayed
to other structures including the amygdala, ventral striatum, and
vlPFC, where changes in behavioural and emotional output may be
further modulated. It remains unclear whether mPFC is involved
in the voluntary modulation of affective responding to stimuli
that remain predictive of aversive consequences. One possibility,
favoured here, is that whereas mPFC is important for regulat-
ing the impact of previous conditioned associations that are no
longer valid, other regions such as dorsal prefrontal cortex and
vlPFC are more involved in controlling the impact of existing valid
conditioned associations or unconditioned responses on target
behaviours and emotional states.
It has been argued here that attention-based theoretical models
of dorsal prefrontal cortex function best account for the collective
decision making and emotion regulation data. According to this
perspective, the role that dorsal regions of prefrontal cortex play
in resolving perceptual conflict (e.g., as occurs in the Stroop task)
also play a critical role in resolving reward-related and emotional
conflict. Thus, dorsal prefrontal cortex resolves decision conflict by
increasing the salience of specific decision-objects (e.g., in the lab
these are specific buttons, levers or decks of cards) or reinforce-
D.G.V. Mitchell / Behavioural Brain Research 217 (2011) 215–231
ment information through interactions with temporal cortex .
This contribution is considered particularly important for learning
ment contexts. A similar attentional process is thought to facilitate
emotion regulation. In this context, dorsal prefrontal cortex is
involved in strengthening the salience of alternative representa-
tions in temporal cortex (e.g., semantic associations or stimulus
features) that are emotionally discordant with the stimulus that
elicited the initial reaction (e.g., [190,199]). In accordance with
biased competition models of attention, these alternate repre-
sentations compete in an inhibitory fashion with those originally
involved in initiating the emotional response. Such competition
has been shown to modulate activity in the amygdala [82,188]
and mPFC [143,144,194].
5.1.1. Future directions
The present review integrates data concerning the involvement
of ventrolateral, medial, and dorsal prefrontal cortices in decision
making and emotion regulation, and provides an informal neu-
rocognitive model of the neural regions that are implicated in
recent theoretical formulations, there are several components of
the model that remain speculative. For example, very little pub-
lished data involving patients with focal vlPFC lesions exist. As
a consequence, the extent to which this region is necessary to
perform relatively simple versus more complex forms of decision
making is unclear. More lesion data are also needed to verify the
importance and role for this region in emotion regulation. A fair
degree of ambiguity exists in the emotion regulation literature
concerning the functional role of pgPFC. Some theories empha-
size the extinction of existing emotional associations, and others
processes co-exist within mPFC, what determines which process is
engaged, and how might the inputs or downstream targets differ?
Another unanswered question concerns the relative importance of
the ventral and dorsal streams for emotion regulation. Are the ven-
tral and dorsal regulatory networks described here activated in a
complimentary fashion, or is each system designed to address a
distinct form of dysregulation? One possibility, favoured here, is
that mPFC is particularly important for regulating affective output
to stimuli that no longer predict the original expected outcome.
In contrast, to control the impact of unconditioned reinforcers or
existing valid conditioned associations on the target behaviour or
emotional state, dorsal regions of prefrontal cortex become more
This work was supported in part by a grant from the Natural
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