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The Journal of Neuroscience, August 27, 2003, 23(21):7931-7939
 Previous Article | Next Article 
Dissociating Valence of Outcome from Behavioral Control in Human Orbital and Ventral Prefrontal Cortices
John O'Doherty,
Hugo Critchley,
Ralf Deichmann, and
Raymond J. Dolan
Wellcome Department of Imaging Neuroscience, Institute of Neurology,
London WC1N 3BG, United Kingdom
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Abstract
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The precise role of orbitofrontal cortex (OFC) in affective processing is
still debated. One view suggests OFC represents stimulus reward value and
supports learning and relearning of stimulus-reward associations. An alternate
view implicates OFC in behavioral control after rewarding or punishing
feedback. To discriminate between these possibilities, we used event-related
functional magnetic resonance imaging in subjects performing a reversal task
in which, on each trial, selection of the correct stimulus led to a 70%
probability of receiving a monetary reward and a 30% probability of obtaining
a monetary punishment. The incorrect stimulus had the reverse contingency. In
one condition (choice), subjects had to choose which stimulus to select and
switch their response to the other stimulus once contingencies had changed. In
another condition (imperative), subjects had simply to track the currently
rewarded stimulus. In some regions of OFC and medial prefrontal cortex,
activity was related to valence of outcome, whereas in adjacent areas activity
was associated with behavioral choice, signaling maintenance of the current
response strategy on a subsequent trial. Caudolateral OFC-anterior insula was
activated by punishing feedback preceding a switch in stimulus in both the
choice and imperative conditions, indicating a possible role for this region
in signaling a change in reward contingencies. These results suggest
functional heterogeneity within the OFC, with a role for this region in
representing stimulus-reward values, signaling changes in reinforcement
contingencies and in behavioral control.
Key words: reward; instrumental learning; behavioral control; orbitofrontal cortex; event-related; fMRI
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Introduction
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The orbitofrontal cortex (OFC) is arguably the least understood subdivision
of prefrontal cortex (PFC). According to one view, OFC represents stimulus
reward value and subserves learning and relearning of associations between
arbitrary neutral stimuli and rewards or punishments
(Rolls, 2000 ). Consistent with
this, single-unit studies in nonhuman animals and human neuroimaging studies
report OFC responses during the presentation of rewarding or punishing stimuli
in different modalities (Thorpe et al.,
1983; Critchley and Rolls,
1996; Zald and Pardo,
1997; Small et al.,
1999; Elliott et al.,
2000a; Breiter et al.,
2001; Gottfried et al.,
2002).
An alternative view proposes that OFC is involved in response selection in
the context of rewarding or punishing outcomes, especially in the inhibition
or suppression of responses that were previously associated with reward
(Dias et al., 1996;
Elliott et al., 2000b;
Roberts and Wallis, 2000).
Evidence for the response selection/inhibition hypothesis arises predominantly
from lesion studies conducted in both nonhuman primates and human patients, in
which during performance of instrumental reward tasks, OFC lesions lead to
difficulties in extinguishing or switching responses from a previously
rewarded stimulus once contingencies have altered and that stimulus is no
longer rewarded (Butter, 1969;
Iversen and Mishkin, 1970;
Rolls et al., 1994;
Dias et al., 1996).
The aim of this study was to determine whether activity in the OFC and in
adjacent ventromedial and lateral prefrontal cortices related to response
selection could be distinguished from that to rewarding and punishing feedback
itself. To accomplish this, we used a probabilistic reversal task in which the
average magnitude of rewards and punishments obtainable after choice of the
correct or incorrect stimulus was kept constant. The only factor that
distinguishes the correct and incorrect stimuli is the probability of
obtaining a reward or punishment. A similar design was used in an
event-related functional magnetic resonance imaging (fMRI) study by Cools et
al. (2002). However, these
authors did not obtain signal in the OFC because of susceptibility artifact,
so it was not possible to distinguish positive and negative feedback from
response selection in this region.
In the present study, we used two main conditions
(Fig. 1). In the
"choice" condition, on each trial, subjects were free to choose
what stimulus to select and could change their choice of stimulus on any
trial. In the "imperative" condition, subjects were rewarded and
punished after the selection of a stimulus, but this time they did not choose
which stimulus to select. Instead, the choice was made for them by the
computer. Within the choice condition, comparisons could be performed between
punishment trials, which were followed by a change in stimulus choice to
punishment trials that were not followed by this change, thus isolating neural
events signaling response switching from neural events related to punishment
itself. Comparisons between the choice and imperative tasks also provided a
means to examine the effects of response selection, because these mechanisms
were predicted to be engaged only in the choice condition.
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Figure 1. Illustration of task display for choice and imperative reversal task.
Subjects were presented with two abstract visual stimuli. At the beginning,
one stimulus was designated the correct stimulus and the other the incorrect
stimulus. In the choice task, subjects selected a stimulus, which then
increased in brightness and was followed by a monetary outcome (winning or
losing 10 or 20 pence). In the imperative task, subjects did not select the
stimulus, but instead this selection was made by computer. Subjects had to
respond to indicate which of the two stimuli had been selected and then
received rewarding and punishing feedback.
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Materials and Methods
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Subjects
Fifteen healthy right-handed normal subjects, 10 of whom were female, were
included in the experiment. The subjects were preassessed to exclude those
with a prior history of neurological or psychiatric illness. All subjects gave
informed consent, and the study was approved by the local research ethics
committee.
Choice reversal task description
Two unfamiliar and easily discriminable fractal patterns were displayed on
a gray background, positioned to the left and right of a central fixation
cross. The total score was displayed numerically in the center of the screen
above a fixation cross. The two fractals were assigned randomly to either the
left or the right of the screen on each trial. After a subject selected a
stimulus, the chosen stimulus increased in brightness, and 1 sec later a
message appeared below the stimulus, indicating how much money the subject had
won or lost, together with a picture of the amount won or lost (which was
either an image of a 20 pence or 10 pence piece)
(Fig. 1). On losing trials, a
red cross was superimposed over the image of the amount lost. The feedback
remained on the screen for 1.3 sec, which then cleared, to be followed by a
fixation cross. The next trial was triggered after 2000 msecs.
At the beginning of the task, one of the stimuli was arbitrarily designated
the "correct stimulus," and the other the "incorrect"
stimulus. Selection of the correct stimulus led to a monetary win with
probability of 0.7 and a monetary loss with probability of 0.3. Selection of
the incorrect stimulus led to a monetary win with probability of 0.3 and a
monetary loss with probability of 0.7. Consistent selection of the correct
stimulus, therefore, led to an overall monetary gain. Conversely, consistent
selection of the incorrect stimulus led to an overall monetary loss. The
magnitudes of rewards and punishments also varied, in that on trials in which
a monetary reward occurred, there was an equal probability that it would be 10
pence or 20 pence. Similarly, on trials in which a monetary loss was received,
there was an equal probability that it would be 10 pence or 20 pence.
Criterion was five touches of the correct stimulus. Once criterion was
reached, reversal occurred after a Poisson process, such that there was a
probability of 0.25 that a reversal took place on any given post-criterion
trial. Once reversal occurred, another reversal was not triggered until
criterion was reached on the new correct stimulus.
Imperative reversal task description
The imperative reversal task was identical to the choice reversal task in
terms of presentation (although two different fractal stimuli were used),
except that in this case subjects had no choice about which stimulus they
would select on a given trial. Instead, the computer selected one of the
stimuli according to the selections made and feedback obtained by another
subject while performing the choice task. Thus, each subject's imperative task
was yoked to the choice condition of another subject.
As in the choice task, each trial began with the presentation of two
arbitrary neutral stimuli on either side of a fixation cross. Unlike the
choice task, 500 msecs into the trial, one of the two stimuli spontaneously
increased in brightness, indicating that the computer had chosen that
stimulus. Once a stimulus had been chosen, but before feedback was obtained,
subjects were instructed to make a response indicating whether the selected
stimulus was on the left or right of the screen. This ensured that subjects
were attending to the relevant stimulus, as well as enabling motor confounds
to be removed in comparisons with the choice task.
Experimental procedure Prescanning training phase.
Before scanning, subjects were trained with a modified version of the
choice reversal task used in the scanner. Subjects were instructed in the
first instance that they had to find out which one of the two stimuli was
correct, without any reference to the fact that contingencies would reverse.
Once subjects had reached criterion for the first time (which in the case of
the training task was 10 selections of the correct stimulus), a message on the
screen informed them that they had found the correct stimulus (this message
was only present in the training phase). The task was then paused, and
subjects were instructed that once the task resumed, the contingencies would
at some point reverse. The subjects were told that they had to work out when a
reversal occurred and then switch their choice of stimulus. The stimuli used
in the training task differed from the ones used during the actual scanning
phase. Training was complete once subjects had attained at least two reversals
after the first acquisition. Subjects were informed that at the end of the
study they would be able to keep the total amount of money accumulated during
task performance when in the scanner (for both the choice and imperative
tasks). This total amount did not exceed 10 pounds for any subject, and at the
end of the experiment, subjects were paid 10 pounds irrespective of their
individual performance.
Scanning phase. The task was presented on a projector screen
positioned  10 cm away from the subject's face. On each trial, the subject
used one of two buttons to select the stimulus positioned on either the left
or right side of the screen. The order of presentation of the choice and
imperative tasks was counterbalanced across subjects. To rule out
stimulus-specific effects, the six fractal stimuli used in the experiment
(including the two used in the prescanning training phase) were randomly
assigned to either the training phase or the choice or imperative tasks for
each individual subject. Subjects performed the choice and imperative tasks in
two separate 15 min sessions. In each session, 60 low-level baseline trials
were randomly intermixed with the task-related trials. These involved the
presentation of a fixation cross for 3 sec. Subjects completed an average of
184 task-related trials in the 15 min provided.
Imaging procedure
The functional imaging was conducted by using a 2 Tesla Siemens Vision MRI
scanner to acquire gradient echo T2*-weighted echo-planar images
images with blood oxygenation level-dependent contrast. We used a special
sequence designed to optimize functional sensitivity in the OFC and medial
temporal lobes (Deichmann et al.,
2003). This consisted of tilted acquisition in an oblique
orientation at 30* to the anterior-posterior commissure line, as
well as application of a preparation pulse with a duration of 1 msec and an
amplitude of -2 mT/m in the slice selection direction. This sequence has been
shown to produce robust activation in the OFC and medial temporal lobes in a
previous study (Gottfried et al.,
2002). The sequence enabled 39 axial slices of 3.67 mm thickness
and 3 mm in-plane resolution to be acquired with a repetition time of 2.78
sec. Subjects were placed in a light head restraint within the scanner to
limit head movement during acquisition. A T1-weighted structural image was
also acquired for each subject. Functional imaging data were acquired in two
separate 15 min (336 vol) sessions in each subject during performance of the
choice and imperative tasks.
Image analysis
The images were analyzed using SPM99 (Wellcome Department of Imaging
Neuroscience, London, UK). To correct for subject motion, the images were
realigned to the first volume (Friston et
al., 1995). The images were then spatially normalized to a
standard T2* template with a resampled voxel size of 3
mm3, and spatial smoothing was applied using a Gaussian kernel with
a full width at half-maximum of 8 mm. Intensity normalization and high-pass
temporal filtering (using a filter width of twice the minimum inter-trial
interval) were also applied to the data.
Statistical analysis
Statistical analysis was carried out using the general linear model, in
which each single event was modeled as a delta function convolved with the
hemodynamic response function and its temporal derivative.
Events were divided up into positive (reward) and negative outcomes,
according to whether money was won or lost after stimulus selection. The time
of onset of each event was locked to the point in the trial when the subject
received the outcome after having made a stimulus selection. We differentiated
between negative outcomes that led to a switch of stimulus choice on the next
trial and negative outcomes that did not lead to such a switch.
In a preliminary analysis, we subdivided switch events into those that
occurred after five or more consecutive selections of the previously chosen
stimulus and those that did not. The rationale for this was to determine
whether switch events that occurred after a subject had responded consistently
to a particular stimulus could be differentiated from more spontaneous switch
events in which the subject had not previously established a persistent
response-set to the other stimulus. The majority of switch events occurred
after five or more selections (mean number of such events across subjects,
14.7), the next most frequent switch event was that after two or less previous
selections of the other stimulus (mean number across subjects, 11.3). Events
with three or four consecutive selections were the least common (mean, 5.3
events across subjects). In the main analysis reported here, we pooled over
all switch events irrespective of the number of selections of the previous
stimulus, because the preliminary analysis did not reveal any significant
differences (at p < 0.001) between the two types of switch event
defined above.
We only modeled positive outcomes not leading to a switch of stimulus
choice, because switches after a rewarding outcome were rare (mean occurrence,
3.8 events across subjects). The two different outcome magnitudes (10 and 20
pence) were also modeled separately for each event type. For each individual
subject, motion parameters were included as regressors of no interest for both
sessions, to take into account additional effects of head motion not removed
at the motion correction stage.
Linear contrasts were performed between the regressors to test for
differential effects at the single subject level. These were then taken to the
group random effects level by performing one-sample t tests on the
contrast images derived from each single subject. In the main analysis
reported here, we averaged over the different outcome magnitudes for each
event type.
We tested for the effects of valence by comparing trials in which rewards
(reward) were obtained with trials in which punishments were obtained that
were not followed by a subsequent switch of stimulus choice (pun_noswch). We
tested for the effects of response selection by comparing trials that were not
followed by a change in stimulus choice on the subsequent trial (reward and
pun_noswch trials) with those that were followed by a switch in stimulus
choice (pun_swch trials). The contrast to detect areas with increased
responses during trials not preceding a switch in stimulus was: [reward +
pun_noswch]/2 - pun_swch, whereas the inverse contrast detected areas with
increased activity during punishing trials preceding a switch in stimulus
choice. We also tested for a difference in the effects of valence and response
selection between the choice and imperative conditions by subtracting the
relevant contrast in the choice condition from that in the imperative
condition. Furthermore, we also tested for common activations relating to
valence and response selection in the choice and imperative tasks by
performing a conjunction analysis between the relevant contrasts from the two
conditions.
We report results at p < 0.001 uncorrected for multiple
comparisons in regions of interest, which we define for the purposes of this
study as being in the OFC and adjacent ventral medial and lateral prefrontal
cortices, as well as anterior cingulate cortex, amygdala, and striatum.
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Results
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Valence of outcome
Regions showing valence-related responses are summarized in
Table 1 and detailed below.
Reward > punishment
Areas showing greater responses to reward than punishment (in the absence
of a behavioral switch) in the choice task include medial PFC and left lateral
OFC (Fig. 2). In the imperative
task, effects were found in the medial OFC/subgenual cingulate, left
caudolateral OFC, and bilateral amygdala (on the right, the locus of
activation is at the border of ventral amygdala). A conjunction of
reward-punishment trials between the choice and imperative tasks revealed
effects in medial PFC, medial OFC/subgenual cingulate cortex, right ventral
striatum, and bilateral amygdala (Fig.
3).
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Figure 2. Areas of ventral PFC showing reward-related responses in the choice task.
A, Group random effects results are shown superimposed on coronal and
sagittal slices from the subject-averaged structural MRI image [at the
Montreal Neurological Institute (MNI) coordinates indicated in the top right
corner of each image]. Significant effects are shown at p < 0.001
in yellow, and to show the full extent of the activations, at p <
0.01 in red. A plot of effect sizes from medial PFC (the area circled) is
shown for each trial type (reward, pun_noswch and pun_swch). B,
Results from the same contrast are shown for a subset of single subjects
superimposed on each subject's individual structural MRI. The threshold is set
at p < 0.01 for illustration.
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Figure 3. Areas activated in conjunction of reward-pun_noswch contrast between the
choice and imperative tasks. Group random effects results are shown
superimposed on coronal slices at the MNI coordinates indicated (top right
corner of each image). Significant effects are shown at p < 0.001
in yellow and at p < 0.01 in red (to show the full extent of the
activations). mPFC, Medial PFC; mOFC, medial OFC; lOFC, lateral OFC; nACC,
nucleus accumbens; Amyg, amygdaloid area.
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Punishment > reward
In the choice task, right dorsal insula showed increased activity to
punishing relative to rewarding outcomes, as well as part of the ventral
lateral PFC. No significant effects were detected in the OFC. In the
imperative tasks, significant effects were found only in a part of dorsal
anterior cingulate cortex. Furthermore, a conjunction analysis revealed common
activity to punishing-rewarding outcomes in the right lateral PFC.
Response selection
Areas showing response selection-related effects in the choice task are
listed in Table 2 and detailed
below.
Response maintenance > response switching
Regions with increased activity during trials in the choice task in which
the subject maintained responding to the current stimulus on the subsequent
trial were medial OFC, right central OFC, and medial PFC, as well as a part of
the left lateral OFC. Group random effects results from orbital and medial PFC
are shown in Fig. 4, together
with activation maps and evoked-response plots from a subset of single
subjects. A direct comparison of pun_noswch to pun_swch events revealed
significant differences between these two event types at the coordinates
described above, albeit at a lower threshold of p < 0.005. For
comparison, areas demonstrating response maintenance effects and areas
sensitive to rewarding outcomes are shown superimposed on the same structural
MRI in Figure 5.
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Figure 4. Areas related to response maintenance in the choice task. A, Group
random effects results are shown superimposed on coronal and sagittal slices
from the subject-averaged structural MRI image (at the MNI coordinates
indicated in the top right corner of each image). Significant effects are
shown at p < 0.001 in yellow and at p < 0.01 in red
(to show the full extent of the activations). A plot of effect sizes from
medial OFC (the area circled) is shown for each trial type (reward,
pun_noswch, and pun_swch). B, Results from the same contrast are
shown for a subset of single subjects superimposed on each subject's
individual structural MRI. The threshold is set at p < 0.01 for
illustration. C, Plots of fitted event-related responses obtained
from peak voxels in medial OFC of each single subject shown in B.
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Figure 5. Valence (reward-punishment) and response maintenance-related effects in the
choice task. Activations related to rewarding outcomes and response
maintenance are shown superimposed on the same coronal and sagittal slices.
Reward-related effects are shown in red (at p < 0.01) and yellow
(at p < 0.001), and response maintenance-related effects are shown
in blue (at p < 0.01) and cyan (at p < 0.001).
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Response switching > response maintenance
Areas with increased activity on trials immediately preceding a switch of
stimulus in the choice were a part of right agranular insula extending into
caudolateral OFC and dorsal anterior cingulate cortex
(Fig. 6A). The direct
contrast of pun_swch - pun- _noswch also revealed significant activation in
this agranular transitional region at p < 0.001, with a separate
locus in caudolateral OFC, providing evidence that this area is not related to
punishment per se but is activated only during punishing outcomes
that are followed in the choice task by a subsequent switch in stimulus choice
(Fig. 6B). Activation
maps and evoked responses are shown from two single subjects in
Figure 6C.
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Figure 6. Areas related to response switching in the choice task. A, Group
random effects results of the contrast of pun_swch - [rewacq + pun_noswch]/2
are shown superimposed on coronal and sagittal slices from the
subject-averaged MRI image (at the MNI coordinates indicated in the top right
corner of each image). Significant effects are shown at p < 0.001
in yellow and at p < 0.01 in red (to show the full extent of the
activations). A plot of effect sizes from anterior insula/caudolateral OFC
(the area circled) is shown for each trial type (reward, pun_noswch, and
pun_swch). B, Results from the contrast of pun_swch-pun_noswch at the
group random effects level, showing a separate locus of activity in
caudolateral OFC. C, Results from the contrast pun_swch - [rewacq +
punacq]/2 are shown for a subset of single subjects superimposed on each
subject's individual structural MRI. The threshold is set at p <
0.01 for illustration.
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Direct comparison between choice and imperative tasks
Areas showing significantly greater responses during the choice task than
the imperative task to rewarding-punishing feedback include medial OFC, left
lateral OFC, and right central OFC. Areas showing significantly greater
responses during the choice task than the imperative task to response
maintenance were medial OFC and right central OFC. The reverse contrast to
identify regions responding more to response switching in the choice and the
imperative tasks revealed effects in dorsal anterior cingulate cortex and
striatum (bilateral caudate nucleus and right putamen). Interestingly, no
differential effects were found in this contrast in right insula/caudolateral
OFC.
Response selection or sensitivity to contingency changes?
An alternative interpretation pertaining to response selection-related
activity in the choice task is that rather than signaling whether or not
responses should be maintained or switched, these areas signal whether
contingencies have changed or not. If a change in contingency has not been
detected, then this would be equivalent to signaling that responses should be
maintained in the choice task. Similarly, if a change in contingency has been
detected, then this would be equivalent to signaling that responses should be
altered in the choice task. The way in which these two possibilities can be
disambiguated is if the same areas are recruited during the equivalent
comparisons between response maintenance and response-switching events in the
imperative task as in the choice task. If so, under the assumption that
response selection is present only in the choice task, contingency change
detection would be a more likely explanation of observed OFC activity.
Conjunction of response selection effects between choice and
imperative tasks
A conjunction of response maintenance effects in choice and imperative task
revealed significant effects in the left lateral OFC, right caudate nucleus,
and posterior cingulate cortex. Consistent with the contingency change
interpretation, a conjunction of response-switching effects in the choice task
with the equivalent contrast in the imperative task revealed activity in the
same region of bilateral caudolateral OFC-anterior insula found to be
associated with response switching in the choice task (above). This is shown
in Figure 7.
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Figure 7. Response switching or contingency change detection? Effects of a
conjunction of the contrast of pun_swch - [rewacq + punacq]/2 between the
choice and imperative tasks is shown superimposed on a coronal slice from the
subject averaged MRI image (at the MNI coordinate shown top right). This
result illustrates that anterior insula/caudolateral OFC is recruited during
both the choice and imperative tasks, suggesting that this area may be more
related to detection of contingency changes than response inhibition per se.
Significant effects are shown at p < 0.001 in yellow and at
p < 0.01 in red (to show the full extent of the activations).
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Discussion
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In this study, we show that different subregions of ventral PFC have
distinct roles during affective learning. First, regions of medial and orbital
PFC are involved in representing outcome, with increased responses to
rewarding outcomes. This finding is consistent with previous studies
(Breiter et al., 2001;
Knutson et al., 2001;
O'Doherty et al., 2001;
Elliott et al., 2003).
Furthermore, although outcome-related activity was evident during both choice
and imperative conditions, we also show in a direct contrast of
choice-imperative conditions that outcome-related activity in medial and
central OFC was greater during the choice than imperative conditions. This may
reflect cognitive modulation of outcome representations, in that in the choice
task, knowledge of the value of outcomes is critical for future behavioral
choice, whereas this is not the case in the imperative task.
Here, the main finding is that responses in ventromedial and orbital cortex
do not merely represent valence of outcome but also signal subsequent
behavioral choice. In the choice task, enhanced responses in medial and left
lateral OFC were evident to both rewarding and punishing feedback not followed
by a change of stimulus choice, relative to punishing feedback that was
followed by a change in behavior. This suggests that after the receipt of
outcomes on the previous trial, activity in ventral PFC predicts the
behavioral decision of the subject on the subsequent trial. Furthermore, parts
of medial and central OFC were significantly more active during the choice
condition than the imperative condition. The implication of this finding is
that these areas may be engaged under conditions when behavioral decision
making is required. This result is compatible with the idea that orbitofrontal
and medial PFC is involved in integrating rewarding and punishing feedback for
affective decision making (Bechara et al.,
2000; Krawczyk,
2002).
We observed a different pattern of responses in agranular insula,
contiguous with caudolateral OFC. Once again, in the choice task, activity in
this region was related to behavioral choice. However, effects were in the
opposite direction to that found in anterior medial and lateral OFC. As shown
in Figure 3, activity in this
region was increased when subjects received punishing feedback that on the
following trial was associated with a switch in stimulus choice. This region
was not engaged by a punishing stimulus in which the subject did not
subsequently switch stimulus choice, or by rewarding stimuli. We note that the
locus of this activity is close to but more ventral than coordinates reported
by Cools et al. (2002), as an
area activated immediately preceding a reversal of stimulus choice.
Interestingly, a conjunction of switch versus stay outcomes between the choice
and imperative tasks revealed significant effects in this region bilaterally.
The finding of activity in this region during the imperative as well as choice
tasks complicates an interpretation that activity in this region reflects
changes in response selection or inhibition of the previously selected
response. An alternative explanation is that in the imperative task, even
though subjects do not choose responses, they do, on average, detect a change
in contingencies on trials preceding a switch in stimulus (given that the
imperative trials from one subject are yoked to the choice task from another
subject). Thus, activity in anterior insula/caudolateral OFC may relate to
detection of a change in contingencies or, more specifically, a decrease in
the average reward value of the currently chosen stimulus. These findings
provide an important insight into the nature of deficits at reversal learning
after lesions of orbital PFC (Rolls et
al., 1994; Dias et al.,
1996). Our results argue against a characterization of the effects
of such lesions as being caused by a difficulty at inhibiting the previously
selected response (Roberts and Wallis,
2000). Rather, our results suggest that lesions of this area may
impair the ability to detect a change in reward contingencies.
Responses in anterior insula/caudolateral OFC during the choice and
imperative tasks can be contrasted with that of dorsal anterior cingulate
cortex. This region was active during punishing trials preceding a switch in
the choice task. Moreover, this region was significantly more active during
the choice task than the imperative task. These findings are consistent with
an fMRI study of a reward-based motor selection task (which was essentially a
reversal task) by Bush et al.
(2002). These authors reported
anterior cingulate responses related to a decrease in reward that was also a
precursor to a shift in action choice. The finding in the present study that
activity in this part of anterior cingulate cortex was modulated by choice
suggests that this area is not merely involved in detecting a change in reward
value, but that it is particularly related to signaling a shift in response
strategy after a change in contingencies. This interpretation is compatible
with the proposal by Shima and Tanji
(1998) that neurons in dorsal
anterior cingulate cortex are involved in the voluntary control of
reward-based movements. This result could also be compatible with observed
anterior cingulate involvement in the generation and control of autonomic
arousal states, particularly during volitional task engagement (Critchley et
al.,
2001a,b,c).
Within this conceptual model, cingulate-driven autonomic responses may
prospectively facilitate behavioral response switching.
Elliott et al. (2000b), on
the basis of a review of neuroimaging findings, proposed a refinement of the
response selection/inhibition hypothesis, in which medial OFC is suggested to
be involved in the monitoring of reward values and lateral OFC is suggested to
be involved in the inhibition or suppression of previously rewarded responses.
In a previous neuroimaging study of a reversal learning paradigm, O'Doherty et
al. (2001) found differential
responses in OFC to abstract reward and punishment (play money), such that
medial OFC was more activated after rewarding feedback, and lateral OFC was
more activated after punishment. These findings were interpreted as indicating
that medial and lateral OFC are differentially involved in representing
abstract rewards and punishments, respectively. We note that in this previous
study, signals related to response selection and valence of outcome were
confounded. Other studies have also found medial-lateral dissociations for
rewarding versus punishing stimuli (Small
et al., 2001; Gottfried et
al., 2002; O'Doherty et al.,
2003). Nevertheless, in the present study, we did not observe a
clear dissociation between medial and lateral OFC. Consistent with previous
findings, we did obtain activity in medial orbital/medial PFC-related to
rewarding outcomes. However, contrary to previous results, parts of left
lateral OFC also showed increased activity to reward, indicating that lateral
OFC can, under some circumstances, be activated by rewarding outcomes
(Elliott et al., 2003). This
cautions against a simple interpretation of medial and lateral OFC functional
dissociation in terms of valence or even response selection. One caveat in
relation to the current study is that there was also an anticipatory component
on each trial, because there was a 1 sec interval after stimulus selection
before outcome presentation. It should be noted in the study by Elliott et al.
(2003), in which lateral
orbital activity was also observed to reward, the authors used a block design
that did not control for expectation-related effects. This raises the
possibility that in our study and that of Elliott et al.
(2003), responses in lateral
OFC to reward may relate to an anticipatory component.
In addition to outcome valence-related activity in PFC, significant effects
were also found in amygdala and ventral striatum to rewarding versus punishing
feedback. Interestingly, these results emerged in a conjunction across task,
although significant effects were present in amygdala in the imperative task
alone. The fact that these areas did not come out in the difference between
choice and imperative tasks suggests that these areas are not modulated in the
same manner as ventral PFC by the degree to which feedback is required for
behavioral choice. Significant effects of reward in amygdala and nucleus
accumbens have also been reported in previous studies
(Knutson et al., 2001;
Elliott et al., 2003). In the
case of nucleus accumbens, activity may be related to reward prediction rather
than being related to feedback itself
(Knutson et al., 2001;
Pagnoni et al., 2002).
Amygdala responses have also been found in previous studies to be related to
anticipation of reward (Knutson et al.,
2001; O'Doherty et al.,
2002).
To conclude, our findings suggest a heterogeneous response profile in human
orbital medial and lateral prefrontal cortices during performance of an
affective learning choice task. Some regions represent valence irrespective of
behavioral choice, other regions are sensitive to response maintenance, and
other regions are involved in detecting a change in contingencies. In future
neuropsychological investigations, it will be of interest to determine whether
discrete lesions in subregions of ventral PFC produce distinct behavioral
deficits in reversal learning along the lines described here, by testing for
differences in the effects of lesions of anterior insula-caudolateral OFC and
ventromedial PFC. The results of the present study are compatible with the
hypotheses that orbital and adjacent cortices are involved in representing
rewarding and punishing feedback, as well as being critically involved in
decision making and behavioral choice.
|
Footnotes
|
|---|
Received April 16, 2003;
revised May 29, 2003;
accepted June 26, 2003.
R.J.D. is supported by a Wellcome Trust Programme grant. H.C. is supported
by a Wellcome Clinician Scientist Fellowship award.
Correspondence should be addressed to Dr. John O'Doherty, Wellcome
Department of Imaging Neuroscience, 12 Queen Square, London WC1N 3BG, UK.
E-mail:
j.odoherty{at}fil.ion.ucl.ac.uk.
Copyright © 2003 Society for Neuroscience
0270-6474/03/237931-09$15.00/0
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Top
Abstract
Introduction
