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The Journal of Neuroscience, July 1, 1999, 19(13):5473-5481
Different Contributions of the Human Amygdala and Ventromedial
Prefrontal Cortex to Decision-Making
Antoine
Bechara 1, 2,
Hanna
Damasio 1, 3,
Antonio R.
Damasio 1, 3, and
Gregory P.
Lee 4
Departments of 1 Neurology and 2 Anatomy
and Cell Biology, University of Iowa College of Medicine, Iowa City,
Iowa 52242, 3 The Salk Institute of Biological Studies, La
Jolla, California 92186, and 4 Section of Neurosurgery,
Medical College of Georgia, Augusta, Georgia 30912
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ABSTRACT |
The somatic marker hypothesis proposes that decision-making is a
process that depends on emotion. Studies have shown that damage of the
ventromedial prefrontal (VMF) cortex precludes the ability to use
somatic (emotional) signals that are necessary for guiding decisions in
the advantageous direction. However, given the role of the amygdala in
emotional processing, we asked whether amygdala damage also
would interfere with decision-making. Furthermore, we asked whether
there might be a difference between the roles that the amygdala and VMF
cortex play in decision-making. To address these two questions, we
studied a group of patients with bilateral amygdala, but not VMF,
damage and a group of patients with bilateral VMF, but not amygdala,
damage. We used the "gambling task" to measure decision-making
performance and electrodermal activity (skin conductance responses,
SCR) as an index of somatic state activation. All
patients, those with amygdala damage as well as those with VMF damage,
were (1) impaired on the gambling task and (2) unable to develop
anticipatory SCRs while they pondered risky choices. However, VMF
patients were able to generate SCRs when they received a reward or a
punishment (play money), whereas amygdala patients failed to do so. In
a Pavlovian conditioning experiment the VMF patients acquired a
conditioned SCR to visual stimuli paired with an aversive loud sound,
whereas amygdala patients failed to do so. The results suggest that
amygdala damage is associated with impairment in decision-making and
that the roles played by the amygdala and VMF in decision-making are different.
Key words:
decision-making; conditioning; gambling task; skin
conductance; emotion; amygdala; prefrontal cortex
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INTRODUCTION |
Recent studies have focused on the
role of the ventromedial prefrontal (VMF) cortex in the activation of
somatic states that influence decision-making (Bechara et al., 1996 ,
1997a; Damasio, 1996). Although the somatic marker hypothesis proposes
that both the VMF cortex and the amygdala are components of a neural
system necessary for implementing advantageous decisions (Damasio,
1994), the role of the amygdala in the process has not been tested yet. Therefore, the objectives of this study were (1) to test whether amygdala damage interferes with the process of decision-making and (2)
to test whether the amygdala and the VMF cortex play different roles in
the process.
To measure decision-making, we used the gambling task, a paradigm
designed to simulate real-life decisions in terms of uncertainty, reward, and punishment (Bechara et al., 1994). In the gambling task the
subjects have to choose between decks of cards that yield high
immediate gain but larger future loss, i.e., long-term loss, and decks
that yield lower immediate gain but a smaller future loss, i.e., a
long-term gain. Skin conductance responses (SCRs) are used as an index
of somatic state activation. In previous studies we showed that
choosing advantageously in the gambling task is a correlate of the
development of anticipatory SCRs, which normal subjects begin to
generate before choosing from a risky deck (Bechara et al., 1996,
1997a). Patients with VMF cortex lesions choose disadvantageously in
this task, and their behavior is in fact a correlate of their failure
to acquire anticipatory SCRs (Bechara et al., 1996, 1997a). Our first
hypothesis is that the amygdala is also a critical structure in a
neural system necessary for somatic state activation and for
implementing advantageous decisions. We predict that patients with
bilateral amygdala damage will be similar to VMF patients in terms of
(1) choosing disadvantageously on the gambling task and (2) failing to
develop anticipatory SCRs before selecting a disadvantageous response.
Our second hypothesis is that the poor decision-making after damage to
the amygdala or VMF cortex is the consequence of different kinds of
impairment. The decision-making impairment after amygdala damage is
possibly the indirect consequence of the patients' inability to
experience sufficiently the emotional attributes of a situation that is
charged with emotion, therefore precluding the possibility to evoke
somatic states after winning or losing money and thus precluding the
enactment of a somatic state when deliberating a decision with future
consequences. On the other hand, the decision-making impairment after
VMF damage is related to an inability to integrate effectively all of
the somatic state information triggered by the amygdala as well as
other somatic effectors such as the hypothalamus and brainstem nuclei.
When a normal subject is faced with a decision to select a card from a
specific deck, the neural activity pertaining to this information is
signaled to VMF cortices, which in turn activate the amygdala. This
latter activity would reconstitute a somatic state that integrates the
numerous and conflicting instances of reward and punishment related to
that deck. The final somatic state, indexed by anticipatory SCRs, then
would influence the decision to select from, or avoid, that deck. VMF
damage precludes this process. Therefore, we predicted that the
amygdala patients would fail to generate SCRs when they win or lose
play money in the gambling task. By contrast, the VMF patients would
generate SCRs after winning or losing.
We conducted a further experiment to test the hypothesis that amygdala,
but not VMF, damage precludes or diminishes the ability of subjects to
evoke the emotional attribute of an emotionally charged stimulus. We
tested the ability of subjects to acquire SCRs to visual stimuli that
had been paired repeatedly with an aversive loud sound. Consistent with
previous studies (Bechara et al., 1995; LaBar et al., 1995, 1998), we
predicted that the patients with amygdala, but not VMF, damage would
fail to evoke SCRs when viewing the visual stimuli paired with an
aversive sound.
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MATERIALS AND METHODS |
Subjects. We studied 13 normal subjects as a control
group (seven women and six men; age range from 22 to 58 years with
7-16 years of education) and a brain-damaged group with 10 subjects, which included five amygdala patients (one woman and four men) and five
VMF patients (three women and two men). The patients in the
brain-damaged groups had an age range from 19 to 58 years with 8-18
years years of education, a verbal I.Q. between 86 and 126, and a
performance I.Q. between 88 and 116.
Anatomical analyses. Anatomical analyses were performed on
raw data from high-resolution magnetic resonance scans and
x-ray-computerized tomograms, using the standard procedures of the
Division's Laboratory of Neuroimaging and Human Neuroanatomy. These
include both template plotting (Damasio and Damasio, 1989) and
three-dimensional volume reconstruction, using Brainvox (Damasio and
Frank, 1992; Frank et al., 1997). All lesions at the time of testing
and anatomical analyses were in the chronic stage and stable. The
amygdala patients R.L. and D.B. have had previous anatomical analyses
(Lee et al., 1988a,b, 1995).
The gambling task. We used a computerized version of the
gambling task based on the original as described in Bechara et al. (1994). An automated and computerized method for collecting, measuring, and analyzing SCR data was used instead of the earlier described methods (Bechara et al., 1994, 1996, 1997a, 1998).
In the computerized version of the gambling task, the subject sees the
four decks of cards on a computer screen. The decks are labeled A, B,
C, and D at the top end of each deck. Using a mouse, the subject can
click on a card on any of the four decks. The computer tracks the
sequence of the cards selected from the various decks. Every time the
subject clicks on a deck "to pick a card," the computer generates a
distinct sound (similar to a casino slot machine). The face of the card
appears on top of the deck (the color is either red or black), and a
message is displayed on the screen indicating the amount of money the
subject has won or lost. On the top of the computer screen is a green
bar that changes according to the amount of money won or lost after
each selection. A gain is indicated by a proportionate increase in the
length of the green bar, and a loss is indicated by a proportionate decrease in the bar length. Once the money is added or subtracted, the
face of the card disappears, and the subject can select another card.
The intertrial interval between making two consecutive card selections
can be set by the examiner at the beginning of the task. The total
number of card selections (trials) in the experiment also is set at the
beginning. In the present experiment we set the intertrial interval at
6 sec to allow for psychophysiological recordings (see below). The
total number of trials was set at 100 card selections. The experiment
shuts off automatically when the 100 selection trials are complete.
However, as in previous experiments, the subject was not told in
advance how many cards he/she was going to pick. To score the
performance of the subject on the gambling task, we added the number of
cards picked from decks A and B in each block of 20 cards; we added the
number of cards picked from decks C and D separately in each block of
20 cards.
Each deck of cards is programmed to have 40 cards: 20 of the cards have
a black face and 20 have a red face. The backs of the cards as they
appear on the screen all look the same, like real decks of cards. The
sequence of red and black cards in each deck and the gains and losses
for each card selection are based on the original version of this task
(Bechara et al., 1994). In brief, every 10 cards from deck A over the
course of trials gain $1000, but there are also five unpredictable
punishments ranging from $150 to $350, bringing the total loss to
$1250. Every 10 cards from deck B gain $1000, but there is also one big
punishment for $1250. On the other hand, every 10 cards from deck C or
D amount only to a gain of $500, but the losses are also smaller, i.e.,
$250 (ranging from $25 to $75 in deck C and one $250 loss in deck D),
bringing a net gain of $250. In summary, decks A and B are equivalent
in terms of overall net loss over trials. Similarly, decks C and D are
equivalent in terms of overall net gains. The difference is that decks
A and C have higher frequency but lower magnitude punishment. Decks B
and D have lower frequency but higher magnitude punishment. Thus, decks
A and B are disadvantageous because they cost more in the long run.
Decks C and D are advantageous because they result in an overall gain
in the long run.
In Figure 1 of Bechara et al. (1994), each square on the score sheet
represents a card in a deck. Each square that has a "0" or "a
negative number" corresponds to a red card, and each square without
any marking corresponds to a black card. The computer displays a $100
reward every time the subject picks a card from deck A or B and
displays $50 when the choice is from deck C or D. When a card
corresponding to a square with a "negative number" is picked, the
computer displays a message: "... You have won X dollars, but you
also have lost Y dollars... " (the Y amount corresponds to the
negative number inside the square), and the net loss is reflected
automatically on the green bar on the screen. When a card corresponding
to a square that is blank or with "0" is picked, the subject wins,
and there is no loss. The computer displays the following message:
"... You have won X dollars... "; the gain is also reflected
on the green bar.
We note that the gambling task involves 100 selections of cards, and
there are only 40 cards in each deck. Thus, it is possible to run out
of cards from a given deck. When a given deck runs out of cards, the
subject is instructed to stop picking from that deck and continue
choosing from the remaining decks. In reality, this situation arises
very seldom. The reason is that the task is more difficult than it
appears to be. It is difficult for subjects to be sure whether to pick
constantly from a given deck. Therefore, their selections are
distributed among the different decks, and the decks seldom run out of cards.
In summary, after clicking to turn each card, the subject
receives some money (the amount is displayed on the screen). On some cards the subject both wins money and
pays a penalty (the amounts are displayed on the screen).
Clicking to turn any card from deck A or deck B yields $100; turning
any card from deck C or deck D yields $50. However, the ultimate future
yield of each deck varies because the penalty amounts are higher in the high-paying decks (A and B), leading to a negative balance, and lower
in the low-paying decks (C and D), leading to a final gain. Thus, decks
A and B are "disadvantageous," whereas decks C and D are
"advantageous."
So that they can perform the task, the subjects are given the following
verbal instructions:
1. In front of you on the screen, there are four decks of cards A, B,
C, and D.
2. I want you to select one card at a time, by clicking on the card,
from any deck you choose.
3. Each time you select a card from a deck, the color of the card turns
red or black, and the computer will tell you that you won some money. I
won't tell you how much money you will win. You will find out along
the way. Every time you win, the green bar gets longer.
4. Every so often, however, when you click on a card, the computer
tells you that you won some money, but then it says that you also lost
some money. I won't tell you when you will lose or how much you will
lose. You will find out along the way. Every time you lose, the green
bar gets shorter.
5. You are absolutely free to switch from one deck to another any time
you wish.
6. The goal of the game is to win as much money as possible and, if you
find yourself unable to win, make sure you avoid losing money as much
as possible.
7. I won't tell you for how long the game will continue. You must keep
on playing until the computer stops.
8. You will get this $2000 credit (see the green bar) to start the
game. At the end, we will see how much you won or lost. The red bar
here is a reminder of how much money you borrowed to play the game.
9. It is important to know that the colors of the cards are irrelevant
in this game. The computer does not make you lose money at random.
However, there is no way for you to figure out when the computer will
make you lose. All I can say is that you may find yourself losing money
on all of the decks, but some decks will make you lose more than
others. You can win if you stay away from the worst decks.
SCR recording during the gambling task. Electrodes are
attached to the thenar and hypothenar areas on the palms after the subject is seated in a comfortable chair in front of the computer screen. As the subject performs the task, SCR activity is recorded continuously and collected simultaneously on a Macintosh computer. Each
time the subject clicks the mouse and selects a card, this action is
recorded as a "mark" on the polygram of SCR activity. Each click is
registered as a selection from the specific deck that was chosen. Thus,
SCRs generated in association with a specific card from a specific deck
can be identified precisely on the polygram. Although the intertrial
interval is set at 6 sec, in reality the time interval between two card
selections is longer, because it takes a few additional seconds for the
subject to decide which card to pick next. This time interval varies
from trial to trial. It is on average ~10 sec. During the 6 sec
intertrial interval the decks are displayed continuously on the screen,
and the subject can ponder which deck to choose next. However, if the
subject clicks the mouse to select a card during that time interval,
the computer will not respond, and therefore no record is generated.
The SCRs generated during the task are divided into three categories:
(1) reward SCRs, which are generated after
turning cards for which there is a reward and no penalty; (2)
punishment SCRs, which are generated after
turning a card for which there is a reward and an immediate penalty;
(3) anticipatory SCRs, which are generated previous to
turning a card from any given deck, i.e., during the time period the
subject ponders from which deck to choose. The time windows for the
reward and punishment SCRs are the 5 sec immediately after
the click of a card. SCRs generated during the end of the
reward/punishment window and before the next click of a card
are considered anticipatory SCRs. The current procedure of scoring
these SCRs is automated. The SCR data were acquired via an MP100WS
system (BIOPAC Systems). The data were stored on a Macintosh computer,
and they were analyzed by AcqKnowledge III software for the MP100WS
system. The AcqKnowledge software allows for the performance of
postacquisition mathematical transformations. Also, the software
provides an extensive array of measurements that can be applied to the
collected data. The steps involved in the quantification of
anticipatory, reward, and punishment SCRs entail the following:
1. Elimination of the downdrift in the SCR wave, using a mathematical
transformation function named "Difference." This function measures
the difference (in amplitude) of two sample points that are separated
by 10 samples. Then the difference is divided by the time interval
between the first selected sample and the last selected sample.
2. Measurement of the "area under the curve" in the 5 sec time
window after a card is selected (for reward and punishment SCRs). This is the measurement of the "area under the curve" in the
time window between the end of the 5 sec after a card is clicked and
before the next click of a card (for anticipatory SCRs). The "area under the curve" measurement is similar to the function of an
"integral" except that, instead of using zero as a baseline for
integration, a straight line is drawn between the endpoints of the
selected area to function as the baseline. The area is expressed in
terms of amplitude units (µS) per time interval (seconds).
3. In the case of reward and punishment SCRs, because the time interval
is always 5 sec, we divide each area under the curve measurement by 5. The area measurements per second (µS/sec) from all of the reward SCRs
of the good decks are averaged. Averaging also is performed on all of
the reward SCRs from the bad decks, all of the punishment SCRs from the
good decks, and all of the punishment SCRs from the bad decks. Thus,
for each subject we obtain two dependent variables of reward SCRs (from
good decks and from bad decks) and two dependent variables of
punishment SCRs (from good decks and from bad decks).
4. In the case of anticipatory SCRs, the time interval varies from
trial to trial, but on average it is also ~5 sec. Therefore, each
area measurement from an individual trial is divided by its correspondent time interval. The area measurements per second (µS/sec) from all of the anticipatory SCRs of the good decks are averaged together as are those from the bad decks. Thus, for each subject we obtain two dependent variables of anticipatory SCRs (one
from the good decks and one from the bad decks).
SCR conditioning with a loud sound. We used monochrome color
slides (blue) as the conditioned stimulus (CS), a startling loud and
obnoxious sound (a fog horn) as the unconditioned stimulus (US), and
electrodermal activity (SCR) as the dependent measure of autonomic
conditioning. Each experiment involved (1) a habituation phase in which
four color stimuli (blue, red, green, orange) were presented
repeatedly without the US and (2) a conditioning phase in which the
blue slides were paired with the US. Six presentations of the blue
slides were paired with the US, and six presentations were not; they
served as test stimuli for acquiring the conditioning. The blue slides
that were paired or unpaired with the US were presented at random among
the other colors. Each experiment also involved (3) an extinction phase
in which the blue slides were presented repeatedly without the US.
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RESULTS |
Anatomy
Two of the amygdala patients had suffered childhood encephalitis
and later were subjected to bilateral stereotaxic amygdalotomy for the
treatment of aggressive behavior. The anatomy of their lesions has been
shown in previous publications (Lee et al., 1988a,b, 1995). All of the
other patients were selected from the Patient Registry of the
University of Iowa's Division of Behavioral Neurology and Cognitive
Neuroscience; the anatomy of their lesions is presented in Figure
1.
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Figure 1.
Neuroanatomical findings in the two groups of
brain-damaged patients. A, Bilateral amygdala lesions.
Coronal sections through the amygdala from the three patients in our
Registry show complete bilateral destruction of the amygdala. The
lesions from the two remaining amygdala patients have been shown in
previous publications (Lee et al., 1988a,b, 1995). B,
Bilateral VMF lesions. Shown are mesial and inferior views of the
overlap of lesions from four VMF patients. The lesions from individual
subjects were transferred onto a reference brain by using the
MAP-3 technique (Frank et al., 1997). The coronal section shows
an area of the ventromedial prefrontal cortex where maximum overlap
occurs. The position of the cut is indicated on the brain on the
left. The color bar below shows the color
code corresponding to the number of overlapping lesions. The lesion of
the fifth VMF patient is not part of the MAP-3 image because, as
explained in the text, this patient suffered from a frontal lobe cyst
at age 2. The lack of a clear structural lesion at macroscopic level
precludes the transfer into MAP-3.
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One of the amygdala patients had congenital bilateral amygdala damage
from Urbach-Wiethe disease (Tranel and Hyman, 1990), two had childhood
encephalitis as indicated earlier, and the other two had herpes simplex
encephalitis during adulthood. One of the VMF patients had a frontal
cyst thought to have developed at age 2 years as a result of a head
injury. The cyst has not been removed, and neuroimaging scans show
bilateral compression of the frontal poles and the anterior
ventromedial regions of the prefrontal cortex. The other four VMF
patients had bilateral damage in the ventromedial sector of the frontal
lobes because of meningioma or stroke. None of the patients suffered
from mental retardation. All subjects (controls and patients) provided
informed consent in accordance with the Human Subjects Committee of the
University of Iowa.
All of the amygdala patients had lesions that involved substantial
portions of the amygdala bilaterally. Two of the amygdala patients also
had minimal damage to the hippocampal formation and surrounding
cortices. The other three patients with amygdala lesions had damage
that included the hippocampus and surrounding cortices (Fig. 1). All of
the VMF patients had lesions confined to the ventral and low mesial
sectors of the frontal lobe in both the right and left hemispheres
(Fig. 1).
Behavioral performance
We subdivided the 100 card selections into five blocks of 20 cards
each, and for each block we counted the number of selections from decks
A and B (disadvantageous) and the number of selections from decks C and
D (advantageous). Figure 2 represents the
results as a function of group, block, and deck type. As the task
progressed, normal controls gradually shifted their preference toward
the good decks (C and D) and away from the bad decks (A and B). By contrast, both the amygdala and VMF patients failed to demonstrate this
shift in behavior. By and large, they selected more cards from the bad
decks than from the good decks. A 3 (group) × 2 (deck type: good
vs bad) × 5 (block) ANOVA on the number of cards selected revealed significant interactions between groups and decks
(F2,20 = 12.4; p < 0.05).
The interaction between groups and decks was significant when the
control subjects were compared with the amygdala patients
(F1,16 = 13.9; p < 0.05)
or with the VMF patients (F1,16 = 14.1;
p < 0.05), but not when the amygdala group was
compared with the VMF group.
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Figure 2.
Means ± SEM of the total number of cards
selected from the advantageous versus the disadvantageous decks in each
block of 20 cards, which were made by normal controls and by patients
with bilateral amygdala or VMF cortex lesions. It is shown that control
subjects learn to avoid the bad decks and prefer the good decks.
Amygdala and VMF patients fail to do so.
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When we looked at individual performances, three subjects in the normal
control group (n = 13) showed a disadvantageous
performance, in that they selected more cards from the bad decks than
from the good decks. In the VMF group, however, only one patient (of five patients) behaved in an advantageous manner, choosing more cards
from the good decks than from the bad decks. However, the patient still
selected more cards from the bad decks (A and B) than 1.6 SD above the
average of cards picked from decks A and B by normal controls. All five
amygdala patients behaved as predicted, choosing more cards from the
bad decks than from the good decks. There was no difference in
performance between the amygdala patients who acquired the damage early
and those that had acquired it late in life. However, there was some
difference between the patients who had damage restricted to the
amygdala and those whose damage involved the hippocampus, irrespective
of the time of onset of the lesion. The amygdala patients with
hippocampal sparing performed worse than those with hippocampal damage
(i.e., chose more disadvantageous cards). This observation, however,
does not mean that hippocampal damage somehow improves performance on
the gambling task. The better score on the gambling task of amygdala-
plus hippocampus-damaged patients is the indirect consequence of the
presence of an amnesic syndrome that leads the patients to make a
random sampling of cards. Random sampling brings the performance score
closer to 50 cards from the good decks and 50 cards from the bad decks. By contrast, the patients with only amygdala damage are similar to the
VMF patients in that they are deliberate in their pursuance of a
disadvantageous course of action. Their selection from the bad decks is
more frequent and thus goes farther away from the 50:50 score.
Anticipatory SCRs
Figure 3 shows that normal controls
developed anticipatory SCRs. In amygdala and VMF patients these
anticipatory SCRs were significantly lower in magnitude in comparison
with normal controls. A 3 (group) × 2 (deck type: good vs bad)
ANOVA on these anticipatory SCRs revealed a significant main effect of
groups (F2,20 = 5.2; p < 0.05). Post hoc comparison of these anticipatory SCRs
(Newman-Keuls) revealed significant differences between the
anticipatory SCRs of controls when compared with amygdala
(p < 0.05) or VMF (p < 0.05) patients, but not when the amygdala patients were compared with
the VMF patients. In controls the anticipatory SCRs associated with the
bad decks were significantly higher in amplitude than those associated
with the good decks (p < 0.05). In amygdala and VMF patients no significant differences of amplitude between
anticipatory SCRs from good and bad decks were seen.
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Figure 3.
Means ± SEM of anticipatory SCRs (µS/sec)
generated by controls, amygdala, or VMF patients in association with
the advantageous decks (C and D, white columns) versus
the disadvantageous decks (A and B, black
columns).
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Interestingly, in the three normal subjects who chose
disadvantageously, the mean anticipatory SCRs from the bad decks (0.062 µS/sec) were smaller than the mean from the good decks (0.067 µS/sec). This is quite the opposite from what happened in general in
normal subjects who behaved advantageously. These subjects have a mean
amplitude from the bad decks (0.160 µS/sec) that is higher than that
from the good decks (0.090 µS/sec). These observations are consistent
with the notion that the avoidance of the risky decks is a correlate of
a significant rise in anticipatory SCRs. Most intriguing is the
difference seen within normal subjects, depending on how advantageously
or disadvantageously they choose.
Reward and punishment SCRs
Figure 4 shows that normal controls
generated SCRs after selecting cards for which they received a reward
(reward SCRs) or cards for which they received a reward and a
punishment (punishment SCRs). All of the amygdala patients were
impaired severely in the generation of either reward or punishment
SCRs, although these same patients were able to generate SCRs in
response to a loud sound (see below). However, four of the five VMF
patients generated reward and punishment SCRs in the normal range.
Because of the lack of homogeneity of variance between groups, these
data are not amenable to parametric techniques of statistical analyses. Therefore, we used an appropriate nonparametric method for data analysis. As a group, although the SCRs from the VMF group are somewhat
lower than the control group, Mann-Whitney U tests
comparing the control and VMF groups did not yield a significant
difference (highest U value = 30, p = 0.8; lowest U value = 16, p = 0.1). Thus, only the amygdala patients were impaired. Mann-Whitney
U tests on the SCR measurements from the control and
amygdala groups revealed a significant difference between the groups
(highest U value = 5, p = 0.007; lowest
U value = 1, p = 0.002). Similar Mann-Whitney U tests on the SCR measurements from the VMF
and amygdala groups revealed a significant difference between the groups (highest U value = 3, p = 0.047;
lowest U value = 2, p = 0.028).
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Figure 4.
Means ± SEM of reward and punishment SCRs
(µS/sec) generated by controls, amygdala, or VMF patients in
association with the advantageous decks (C and D, white
columns) or the disadvantageous decks (A and B, black
columns).
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It is interesting to note that the lowering of the average
reward/punishment SCRs in the VMF group was attributable to only one
patient who did not generate SCRs to reward and punishment. Interestingly, this same subject also did not acquire conditioned SCRs
(see below) and thus behaved more like the patients with amygdala
lesions. However, even with the inclusion of this patient the analysis
comparing the VMF with the amygdala group still yielded a significant
difference. This suggests that amygdala and VMF damage exerts distinct
effects on the ability to generate SCRs after reward or punishment is received.
Nonetheless, it is intriguing to speculate why this patient behaved
more like the amygdala than the VMF patients. We began to explore this
issue with more patients. Our preliminary finding is that there may be
an anatomical explanation for the difference. VMF patients who do not
generate punishment and reward SCRs and do not acquire conditioned SCRs
(Tranel et al., 1996) seem to have bilateral ventromedial prefrontal
cortex lesions that extend more posteriorly and probably include the
basal forebrain. Consistent with this observation, the VMF patient in
question does indeed have a lesion that extends into the posterior
region of the prefrontal cortex.
Early trial versus late trial SCRs
The SCR measures (anticipatory vs reward/punishment) obtained in
our study are temporally adjacent. Although there is no evidence in the
psychophysiology literature to support this possibility, we still
considered the possibility that the reward/punishment SCRs observed in
VMF patients were delayed anticipatory SCRs. In other words, it could
be that the anticipatory SCRs in VMF patients would have a slower
emergence so that they would appear at a later time window, i.e., after
selecting the card rather than before. Therefore, we analyzed the data
in terms of early versus late trials. The rationale for this approach
was based on previous studies (Bechara et al., 1996, 1997a), which
showed that the generation of anticipatory SCRs is less evident during the early trials than in the late trials. In normal controls we would
expect to see a rise in anticipatory SCRs as we move from the early to
the late trials. On the other hand, we would anticipate a slight drop
in reward/punishment SCRs (because of habituation) as we move from the
early to late trials. In VMF patients we would not expect a change in
anticipatory SCRs, but we would expect the changes in reward/punishment
SCRs to be similar to those of controls. Control and VMF groups showed
similar changes in reward/punishment SCRs between the two epochs.
However, in relation to the anticipatory SCRs, only the control group
showed the expected change. This comparison rules out the possibility
that VMF patients might have been generating delayed anticipatory SCRs.
Conditioned and unconditioned SCRs
All control subjects showed conditioning in that they began to
generate SCRs after the presentation of a slide previously paired with
a loud sound, and so did four of the five VMF patients. The five
amygdala patients failed to show any conditioned SCRs. Figure
5A shows that the conditioned
SCRs generated by control subjects and VMF patients during the
conditioning phase were significantly higher than those generated
during the habituation or extinction phase (Newman-Keuls tests;
p values < 0.001). The five amygdala patients did not
show any signs of conditioning, and the differences were not
significant (p values > 0.05). Figure
5B reveals that all subjects (controls, VMF, and amygdala)
generated SCRs to the US (loud sound), albeit that the SCRs in the
amygdala patients were lower than those in controls or VMF patients.
Thus, all of the amygdala patients failed to generate SCRs to winning
and losing money (in the previous experiment), and they failed to
acquire the conditioning (present experiment). However, they were able to generate SCRs to a primary US such as a startling loud sound.
View larger version (13K):
[in this window]
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|
Figure 5.
A, Magnitudes of SCRs in the
conditioning phase as compared with the SCRs in the habituation and
extinction phases. Each point on the plot represents the
means ± SEM of the magnitudes of SCRs generated by control
subjects, amygdala, and VMF patients during each phase of the
conditioning experiment. Each Habituation score
represents the mean (from n = 6 controls, 5 VMF,
and 5 amygdala patients) of the mean magnitude of SCRs generated in
response to the last three slides preceding conditioning. Each
Conditioning score represents the mean of the mean
magnitude of SCRs generated in response to six presentations of the CS
(not followed by the US). Each Extinction 1 score
represents the mean of the mean magnitude of SCRs generated in response
to the first three repeated presentations of the CS during extinction.
Each Extinction 2 score represents the mean of the mean
magnitude of SCRs in response to the last three repeated presentations
of the CS. B, Magnitudes of SCRs to the blue slides (CS)
that were paired with the US during conditioning. Each
column represents the mean ± SEM of the mean
magnitude of SCRs generated in response to six presentations of the CS
(paired with the US) from the same control subjects and brain-damaged
patients as in A.
|
|
| |
DISCUSSION |
Our first hypothesis that the amygdala is a critical structure in
a neural system necessary for somatic state activation and for
implementing advantageous decisions is supported by the finding that
amygdala patients failed to generate anticipatory SCRs before selecting
a disadvantageous response. They also performed abnormally in the
gambling task. Support for our second hypothesis, that the amygdala and
VMF cortex play different roles in the process of decision-making,
comes from the finding that there were differences in the profiles of
impairment in the two groups despite some similarities. VMF patients
did generate somatic states when told that they had won or lost play
money, whereas amygdala patients failed to do so. VMF patients did
acquire conditioned SCRs to a loud sound whereas amygdala patients did
not. All patients, however, were capable of generating SCRs to the
presentation of a physical stimulus such as a loud sound.
Decision-making is a complex process that we believe is dependent on
the generation of somatic states (Damasio, 1994). The failure to evoke
somatic states, as happens in both the amygdala and VMF patients,
disturbs the process of making advantageous decisions. However, our
findings suggest that the defective mechanism that led to a failure to
generate somatic states is different in amygdala and VMF patients.
We see the impairment in decision-making after amygdala damage as an
indirect consequence of the role of the amygdala in attaching affective
attributes to stimuli. This interpretation is consistent with the
studies showing that monkeys with lesions of the amygdala have an
increased tendency to approach objects such as snakes (Kluver and Bucy,
1939; Zola-Morgan et al., 1991; Aggleton, 1992), as if the object of
fear can no longer evoke a state of fear. This also is supported by the
present and previous findings (Bechara et al., 1995; LaBar et al.,
1995, 1998) that amygdala damage prevents the development of
conditioned SCRs to visual stimuli paired with an aversive sound. In
addition, numerous experimental studies showed that amygdala damage
interferes with processing the affective attributes of reward stimuli
as well. This effect has been shown in rats with food and sex
reinforcement (Everitt et al., 1989; Hatfield et al., 1996; Robledo et
al., 1996) and in monkeys with food reinforcement (Malkova et al.,
1997). Thus, in humans, after amygdala damage the loss of money can no
longer evoke the somatic state of punishment. Failure to evoke somatic
states after winning or losing money would preclude the reconstitution
of such somatic states when deliberating a decision with future consequences.
Not all of the amygdala patients had selective bilateral amygdala
damage. Three of the patients had substantial damage to the hippocampal
formation and surrounding areas. They suffered from severe anterograde
memory deficit, which could be thought to influence the decision-making
process. Despite these extended lesions and additional impairments, we
do not believe that the decision-making impairment detected in these
patients is related to the nonamygdala damage for two reasons. First,
the two patients who had damage restricted to the amygdala were in fact
those who exhibited the most severe behavioral impairment in the
gambling task. Second, in another study we tested a group of amnesic
patients suffering from anoxic encephalopathy, which is known to damage CA1 cells of the hippocampus rather than the amygdala (Zola-Morgan et
al., 1986; Rempel-Clower et al., 1996). We found that, although amnesiacs do not perform as well as normal controls in the gambling task, they still make predominantly advantageous choices (Bechara et
al., 1997b). Therefore, it is unlikely that the hippocampal damage in
our amygdala patients could be responsible for the findings of
impairment in the gambling task.
The notion that bilateral damage to the amygdala is associated
with decision-making impairments in the gambling task also is supported
by the observation that amygdala patients demonstrate poor judgment and
decision-making in their real-life social behavior (Tranel and Hyman,
1990; Adolphs et al., 1995). Furthermore, some amygdala patients show
an inability to evoke somatic states after winning or losing in
real-life settings (Damasio et al., 1985).
Unlike the amygdala patients, the VMF patients did acquire the SCR
conditioning with an aversive loud sound, and they did generate SCRs
when they won and lost money in the gambling task. This finding is
consistent with the conditioning studies in animals showing that the
VMF cortex is not necessary for the acquisition of fear conditioning
(Morgan and LeDoux, 1995). Similarly, the human VMF cortex, especially
its anterior compartment, is not necessary for conditioning involving
the association of a stimulus with a primary unconditioned stimulus
such as an aversive loud sound (Tranel et al., 1996). This indicates
that, unlike the amygdala, the VMF cortex is not necessary for
mediating the affective attributes of a stimulus charged with emotion.
However, we concede that the VMF cortex may play some role in this
process. Indeed, previous work with VMF patients showed that the
patients failed to generate SCRs to emotionally charged pictures when
they viewed these pictures passively (Damasio et al., 1990). However,
the same patients generated normal magnitude SCRs to the same target
pictures when they were asked to view and describe the content of the
pictures (Damasio et al., 1990). The results suggest that the patients
may have a weakened ability to process the affective attribute of an
emotional stimulus. Perhaps this could explain the slightly lower
magnitude SCRs generated by VMF patients after receiving reward or
punishment, relative to normal control subjects (see Fig. 4). Despite
such a possible weakness, the results show that the VMF patients are not impaired in their ability to generate SCRs to emotionally significant events. This stands in contrast to the amygdala patients who are severely impaired in this domain.
We suggest that the mechanism underlying the decision-making impairment
associated with VMF damage is more complex than that of the amygdala.
After the somatic states of reward and punishment are evoked with
individual card draws, each deck becomes associated with numerous and
conflicting states of reward and punishment. The role of the VMF cortex
comes into play when subjects sort out this conflict and decide whether
to seek or avoid the deck. The poor decision-making associated with VMF
damage is related to an inability to integrate effectively all of the
somatic state information triggered by the amygdala as well as other
somatic effectors such as the hypothalamus and brainstem nuclei.
Indeed, the VMF cortex has extensive bi-directional connections with
the amygdala (Amaral and Price, 1984; Van Hoesen, 1985; Amaral et al., 1992). When subjects decide to select cards from a specific deck,
the neural activity pertaining to this information is signaled to VM
cortices, which in turn activate the amygdala (Damasio et al., 1991).
This latter activity would reconstitute a somatic state that integrates
the numerous and conflicting instances of reward and punishment
encountered with individual card draws from that deck. In the end, if
the negative somatic states outweigh the positive ones, an overall
negative state is enacted and is indexed by the anticipatory SCRs we
observed before the selection of cards from the disadvantageous decks.
In turn, this influences the decision to avoid the deck under consideration.
It is important to note that SCRs are viewed by psychophysiologists as
a measure of only general arousal (Venables and Christie, 1975). Our
SCR measures do not necessarily distinguish between positive and
negative somatic states. This distinction, however, is not relevant to
the goals of this study. Indeed, our punishments SCRs (see Fig. 4) are
not pure responses to punishment. Each of these SCRs was a response to
a reward, followed by a punishment (e.g., you won an X amount... but
you lost a Y amount). Furthermore, SCRs are more sensitive to negative
than positive states (Venables and Christie, 1975). Therefore, it is
likely that the anticipatory SCRs we see in normal subjects (see Fig.
3) reflect increased arousal to the higher losses in the
disadvantageous decks.
The current study parallels the Schoenbaum et al. (1998) study in
animals suggesting that both the orbitofrontal cortex and basolateral
amygdala provide a critical circuit for the learning that underlies
goal-directed behavior (Schoenbaum et al., 1998). Our finding is
significant because the nature of the deficit revealed after VMF or
amygdala damage may reflect two types of decision-making deficits
observable in the behaviors of real-life activities of these patients.
The decision-making impairments of patients with VMF cortex lesions
have remote consequences and usually do not cause bodily harm. For
instance, VMF patients make choices that lead to long-term financial
losses or to the loss of friend and family relationships down the line
(Eslinger and Damasio, 1984), but they never engage in actions that may
lead to physical harm to themselves or to others. On the other hand,
although patients with bilateral amygdala lesions do exhibit
decision-making impairments in the social realm similar to those of the
VMF patients (Tranel and Hyman, 1990; Adolphs et al., 1995), they
actually can pursue actions that eventually lead to physical harm to
themselves and to others. Indeed, with one exception (Adolphs et al.,
1995), amygdala patients who participated in this study live under
supervised care and are unable to function alone in society. In two of
the cases the patients have pursued actions that endangered themselves and others (Lee et al., 1988a,b, 1995).
| |
FOOTNOTES |
Received Jan. 29, 1999; revised April 2, 1999; accepted April 12, 1999.
This work was supported by National Institute of Neurological Diseases
and Stroke Grant PO1 NS19632. We are indebted to the valuable
contribution of Jon Spradling for computerizing the gambling task used
in this study. Also, we are indebted to the contribution of Denise
Krutzfeldt for scheduling the subjects and of Andrea Hindes for testing
some of the subjects in this study.
Correspondence should be addressed to Dr. Antoine Bechara, Department
of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242.
| |
REFERENCES |
-
Adolphs R,
Tranel D,
Damasio H,
Damasio AR
(1995)
Fear and the human amygdala.
J Neurosci
15:5879-5892[Abstract].
-
Aggleton JP
(1992)
The functional effects of amygdala lesions in humans: a comparison with findings from monkeys.
In: The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction (Aggleton JP,
ed), pp 485-504. New York: Wiley-Liss.
-
Amaral DG,
Price JL
(1984)
Amygdalo-cortical connections in the monkey (Macaca fascicularis).
J Comp Neurol
230:465-496[Web of Science][Medline].
-
Amaral DG,
Price JL,
Pitkanen A,
Carmichael ST
(1992)
Anatomical organization of the primate amygdaloid complex.
In: The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction (Aggleton JP,
ed), pp 1-66. New York: Wiley-Liss.
-
Bechara A,
Damasio AR,
Damasio H,
Anderson SW
(1994)
Insensitivity to future consequences following damage to human prefrontal cortex.
Cognition
50:7-15[Web of Science][Medline].
-
Bechara A,
Tranel D,
Damasio H,
Adolphs R,
Rockland C,
Damasio AR
(1995)
Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans.
Science
269:1115-1118[Abstract/Free Full Text].
-
Bechara A,
Tranel D,
Damasio H,
Damasio AR
(1996)
Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex.
Cereb Cortex
6:215-225[Abstract/Free Full Text].
-
Bechara A,
Damasio H,
Tranel D,
Damasio AR
(1997a)
Deciding advantageously before knowing the advantageous strategy.
Science
275:1293-1295[Abstract/Free Full Text].
-
Bechara A,
Tranel D,
Damasio H,
Damasio AR
(1997b)
An anatomical system subserving decision-making.
Soc Neurosci Abstr
23:495.
-
Bechara A,
Damasio H,
Tranel D,
Anderson SW
(1998)
Dissociation of working memory from decision making within the human prefrontal cortex.
J Neurosci
18:428-437[Abstract/Free Full Text].
-
Damasio AR
(1994)
In: Descartes' error: emotion, reason, and the human brain. New York: Grosset/Putnam.
-
Damasio AR
(1996)
The somatic marker hypothesis and the possible functions of the prefrontal cortex.
Philos Trans R Soc Lond [Biol]
351:1413-1420[Web of Science][Medline].
-
Damasio H,
Damasio AR
(1989)
In: Lesion analysis in neuropsychology. New York: Oxford UP.
-
Damasio H,
Frank R
(1992)
Three-dimensional in vivo mapping of brain lesions in humans.
Arch Neurol
49:137-143[Abstract/Free Full Text].
-
Damasio AR,
Eslinger PJ,
Damasio H,
Van Hoesen GW,
Cornell S
(1985)
Multimodal amnesic syndrome following bilateral temporal and basal forebrain damage.
Arch Neurol
42:252-259[Abstract/Free Full Text].
-
Damasio AR,
Tranel D,
Damasio H
(1990)
Individuals with sociopathic behavior caused by frontal damage fail to respond autonomically to social stimuli.
Behav Brain Res
41:81-94[Web of Science][Medline].
-
Damasio AR,
Tranel D,
Damasio H
(1991)
Somatic markers and the guidance of behavior: theory and preliminary testing.
In: Frontal lobe function and dysfunction (Levin HS,
Eisenberg HM,
Benton AL,
eds), pp 217-229. New York: Oxford UP.
-
Eslinger P,
Damasio AR
(1984)
Behavioral disturbances associated with rupture of anterior communicating artery aneurysms.
Semin Neurol
4:385-389[Web of Science].
-
Everitt BJ,
Cador M,
Robbins TW
(1989)
Interactions between the amygdala and ventral striatum in stimulus-reward associations: studies using a second-order schedule of sexual reinforcement.
Neuroscience
30:63-75[Web of Science][Medline].
-
Frank R,
Damasio H,
Grabowski TJ
(1997)
Brainvox: an interactive multimodal visualization and analysis system for neuroanatomical imaging.
NeuroImage
5:13-30[Web of Science][Medline].
-
Hatfield T,
Han JS,
Conley M,
Gallagher M,
Holland P
(1996)
Neurotoxic lesions of basolateral, but not central, amygdala interfere with Pavlovian second-order conditioning and reinforcer devaluation effects.
J Neurosci
16:5256-5265[Abstract/Free Full Text].
-
Kluver H,
Bucy PC
(1939)
Preliminary analysis of functions of the temporal lobes in monkeys.
Arch Neurol Psychiatry
42:979-997[Abstract/Free Full Text].
-
LaBar KS,
LeDoux JE,
Spencer DD,
Phelps EA
(1995)
Impaired fear conditioning following unilateral temporal lobectomy in humans.
J Neurosci
15:6846-6855[Abstract/Free Full Text].
-
LaBar KS,
Gatenby JC,
Gore JC,
LeDoux JE,
Phelps EA
(1998)
Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study.
Neuron
20:937-945[Web of Science][Medline].
-
Lee GP,
Arena JG,
Meador KJ,
Smith JR,
Loring DW,
Flanigin HF
(1988a)
Changes in autonomic responsiveness following bilateral amygdalotomy in humans.
Neuropsychiatry Neuropsychol Behav Neurol
1:119-129.
-
Lee GP,
Meador KJ,
Smith JR,
Loring DW,
Flanigin HF
(1988b)
Preserved crossmodal association following bilateral amygdalotomy in man.
Int J Neurosci
40:47-55[Web of Science][Medline].
-
Lee GP,
Reed MF,
Meador KJ,
Smith JR,
Loring DW
(1995)
Is the amygdala crucial for cross-modal association in humans?
Neuropsychologia
9:236-245.
-
Malkova L,
Gaffan D,
Murray EA
(1997)
Excitotoxic lesions of the amygdala fail to produce impairment in visual learning for auditory secondary reinforcement but interfere with reinforcer devaluation effects in rhesus monkeys.
J Neurosci
17:6011-6020[Abstract/Free Full Text].
-
Morgan MA,
LeDoux JE
(1995)
Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats.
Behav Neurosci
109:681-688[Web of Science][Medline].
-
Rempel-Clower NL,
Zola SM,
Squire LR,
Amaral DG
(1996)
Three cases of enduring memory impairment after bilateral damage limited to the hippocampal formation.
J Neurosci
16:5233-5255[Abstract/Free Full Text].
-
Robledo P,
Robbins TW,
Everitt BJ
(1996)
Effects of excitotoxic lesions of the central amygdaloid nucleus on the potentiation of reward-related stimuli by intra-accumbens amphetamine.
Behav Neurosci
110:981-990[Web of Science][Medline].
-
Schoenbaum G,
Chiba AA,
Gallagher M
(1998)
Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning.
Nat Neurosci
1:155-159.[Web of Science][Medline]
-
Tranel D,
Hyman BT
(1990)
Neuropsychological correlates of bilateral amygdala damage.
Arch Neurol
47:349-355[Abstract/Free Full Text].
-
Tranel D,
Bechara A,
Damasio H,
Damasio AR
(1996)
Fear conditioning after ventromedial frontal lobe damage in humans.
Soc Neurosci Abstr
22:1108.
-
Van Hoesen GW
(1985)
Neural systems of the non-human primate forebrain implicated in memory.
Ann NY Acad Sci
444:97-112[Web of Science][Medline].
-
Venables PH,
Christie MJ
(1975)
Mechanisms, instrumentation, recording techniques, and quantification of responses.
In: Electrodermal activity in psychological research (Prokasy WJ,
Raskin DC,
eds), pp 1-124. New York: Academic.
-
Zola-Morgan S,
Squire LR,
Amaral DG
(1986)
Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus.
J Neurosci
6:2950-2967[Abstract].
-
Zola-Morgan S,
Squire LR,
Alverez-Royo P,
Clower RP
(1991)
Independence of memory functions and emotional behavior: separate contributions of the hippocampal formation and the amygdala.
Hippocampus
1:207-220[Medline].
Copyright © 1999 Society for Neuroscience 0270-6474/99/19135473-09$05.00/0
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|
|
E. YECHIAM, J. E. KANZ, A. BECHARA, J. C. STOUT, J. R. BUSEMEYER, E. M. M ALTMAIER, and J. S. PAULSEN
Neurocognitive deficits related to poor decision making in people behind bars
Psychon Bull Rev,
February 1, 2008;
15(1):
44 - 51.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. L. Keightley, K. S. Chiew, G. Winocur, and C. L. Grady
Age-related differences in brain activity underlying identification of emotional expressions in faces
Soc Cogn Affect Neurosci,
December 1, 2007;
2(4):
292 - 302.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Eldar, O. Ganor, R. Admon, A. Bleich, and T. Hendler
Feeling the Real World: Limbic Response to Music Depends on Related Content
Cereb Cortex,
December 1, 2007;
17(12):
2828 - 2840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. S. Peterson, H. A. Choi, X. Hao, J. A. Amat, H. Zhu, R. Whiteman, J. Liu, D. Xu, and R. Bansal
Morphologic Features of the Amygdala and Hippocampus in Children and Adults With Tourette Syndrome
Arch Gen Psychiatry,
November 1, 2007;
64(11):
1281 - 1291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Morcom, J. Li, and M. D. Rugg
Age Effects on the Neural Correlates of Episodic Retrieval: Increased Cortical Recruitment with Matched Performance
Cereb Cortex,
November 1, 2007;
17(11):
2491 - 2506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. K. Fellows and M. J. Farah
The Role of Ventromedial Prefrontal Cortex in Decision Making: Judgment under Uncertainty or Judgment Per Se?
Cereb Cortex,
November 1, 2007;
17(11):
2669 - 2674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Winstanley, Q. LaPlant, D. E. H. Theobald, T. A. Green, R. K. Bachtell, L. I. Perrotti, R. J. DiLeone, S. J. Russo, W. J. Garth, D. W. Self, et al.
{Delta}FosB Induction in Orbitofrontal Cortex Mediates Tolerance to Cocaine-Induced Cognitive Dysfunction
J. Neurosci.,
September 26, 2007;
27(39):
10497 - 10507.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. G. Berntson, A. Bechara, H. Damasio, D. Tranel, and J. T. Cacioppo
Amygdala contribution to selective dimensions of emotion
Soc Cogn Affect Neurosci,
June 1, 2007;
2(2):
123 - 129.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. Floresco and M. T. Tse
Dopaminergic Regulation of Inhibitory and Excitatory Transmission in the Basolateral Amygdala-Prefrontal Cortical Pathway
J. Neurosci.,
February 21, 2007;
27(8):
2045 - 2057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. Floresco and S. Ghods-Sharifi
Amygdala-Prefrontal Cortical Circuitry Regulates Effort-Based Decision Making
Cereb Cortex,
February 1, 2007;
17(2):
251 - 260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. K. Watson, B. J. Matthews, and J. M. Allman
Brain Activation during Sight Gags and Language-Dependent Humor
Cereb Cortex,
February 1, 2007;
17(2):
314 - 324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Feinstein, M. B. Stein, and M. P. Paulus
Anterior insula reactivity during certain decisions is associated with neuroticism
Soc Cogn Affect Neurosci,
September 1, 2006;
1(2):
136 - 142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. N. DeWall, P. S. Visser, and L. C. Levitan
Openness to Attitude Change as a Function of Temporal Perspective
Pers Soc Psychol Bull,
August 1, 2006;
32(8):
1010 - 1023.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. Knapska, E. Nikolaev, P. Boguszewski, G. Walasek, J. Blaszczyk, L. Kaczmarek, and T. Werka
Between-subject transfer of emotional information evokes specific pattern of amygdala activation
PNAS,
March 7, 2006;
103(10):
3858 - 3862.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Winstanley, D. E.H. Theobald, J. W. Dalley, R. N. Cardinal, and T. W. Robbins
Double Dissociation between Serotonergic and Dopaminergic Modulation of Medial Prefrontal and Orbitofrontal Cortex during a Test of Impulsive Choice
Cereb Cortex,
January 1, 2006;
16(1):
106 - 114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Mobbs, C. C. Hagan, E. Azim, V. Menon, and A. L. Reiss
Personality predicts activity in reward and emotional regions associated with humor
PNAS,
November 8, 2005;
102(45):
16502 - 16506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Izquierdo, R. K. Suda, and E. A. Murray
Comparison of the Effects of Bilateral Orbital Prefrontal Cortex Lesions and Amygdala Lesions on Emotional Responses in Rhesus Monkeys
J. Neurosci.,
September 14, 2005;
25(37):
8534 - 8542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Birbaumer, R. Veit, M. Lotze, M. Erb, C. Hermann, W. Grodd, and H. Flor
Deficient Fear Conditioning in Psychopathy: A Functional Magnetic Resonance Imaging Study
Arch Gen Psychiatry,
July 1, 2005;
62(7):
799 - 805.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Jollant, F. Bellivier, M. Leboyer, B. Astruc, S. Torres, R. Verdier, D. Castelnau, A. Malafosse, and P. Courtet
Impaired Decision Making in Suicide Attempters
Am J Psychiatry,
February 1, 2005;
162(2):
304 - 310.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. W.Y. Mah, M. C. Arnold, and J. Grafman
Deficits in Social Knowledge Following Damage to Ventromedial Prefrontal Cortex
J Neuropsychiatry Clin Neurosci,
February 1, 2005;
17(1):
66 - 74.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. K. Fellows
The Cognitive Neuroscience of Human Decision Making: A Review and Conceptual Framework
Behav Cogn Neurosci Rev,
September 1, 2004;
3(3):
159 - 172.
[Abstract]
[PDF]
|
|
|
|
|
|
|
L. Mah, M. C. Arnold, and J. Grafman
Impairment of Social Perception Associated With Lesions of the Prefrontal Cortex
Am J Psychiatry,
July 1, 2004;
161(7):
1247 - 1255.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Winstanley, D. E. H. Theobald, R. N. Cardinal, and T. W. Robbins
Contrasting Roles of Basolateral Amygdala and Orbitofrontal Cortex in Impulsive Choice
J. Neurosci.,
May 19, 2004;
24(20):
4718 - 4722.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Roozendaal, J. R. McReynolds, and J. L. McGaugh
The Basolateral Amygdala Interacts with the Medial Prefrontal Cortex in Regulating Glucocorticoid Effects on Working Memory Impairment
J. Neurosci.,
February 11, 2004;
24(6):
1385 - 1392.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Pickens, M. P. Saddoris, B. Setlow, M. Gallagher, P. C. Holland, and G. Schoenbaum
Different Roles for Orbitofrontal Cortex and Basolateral Amygdala in a Reinforcer Devaluation Task
J. Neurosci.,
December 3, 2003;
23(35):
11078 - 11084.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. P. Blumberg, J. Kaufman, A. Martin, R. Whiteman, J. H. Zhang, J. C. Gore, D. S. Charney, J. H. Krystal, and B. S. Peterson
Amygdala and Hippocampal Volumes in Adolescents and Adults With Bipolar Disorder
Arch Gen Psychiatry,
December 1, 2003;
60(12):
1201 - 1208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. S. Arana, J. A. Parkinson, E. Hinton, A. J. Holland, A. M. Owen, and A. C. Roberts
Dissociable Contributions of the Human Amygdala and Orbitofrontal Cortex to Incentive Motivation and Goal Selection
J. Neurosci.,
October 22, 2003;
23(29):
9632 - 9638.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Chudasama and T. W. Robbins
Dissociable Contributions of the Orbitofrontal and Infralimbic Cortex to Pavlovian Autoshaping and Discrimination Reversal Learning: Further Evidence for the Functional Heterogeneity of the Rodent Frontal Cortex
J. Neurosci.,
September 24, 2003;
23(25):
8771 - 8780.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Bar-On, D. Tranel, N. L. Denburg, and A. Bechara
Exploring the neurological substrate of emotional and social intelligence
Brain,
August 1, 2003;
126(8):
1790 - 1800.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Lehmann, D. Treit, and M. B. Parent
Spared Anterograde Memory for Shock-Probe Fear Conditioning After Inactivation of the Amygdala
Learn. Mem.,
July 1, 2003;
10(4):
261 - 269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Hornak, J. Bramham, E. T. Rolls, R. G. Morris, J. O'Doherty, P. R. Bullock, and C. E. Polkey
Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices
Brain,
July 1, 2003;
126(7):
1691 - 1712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. Wood
Social Cognition and the Prefrontal Cortex
Behav Cogn Neurosci Rev,
June 1, 2003;
2(2):
97 - 114.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. E. Pinkham, D. L. Penn, D. O. Perkins, and J. Lieberman
Implications for the Neural Basis of Social Cognition for the Study of Schizophrenia
Am J Psychiatry,
May 1, 2003;
160(5):
815 - 824.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Emmerling and C. Cherniss
Emotional Intelligence and the Career Choice Process
Journal of Career Assessment,
May 1, 2003;
11(2):
153 - 167.
[Abstract]
[PDF]
|
|
|
|
|
|
|
G. Schoenbaum, B. Setlow, S. L. Nugent, M. P. Saddoris, and M. Gallagher
Lesions of Orbitofrontal Cortex and Basolateral Amygdala Complex Disrupt Acquisition of Odor-Guided Discriminations and Reversals
Learn. Mem.,
March 1, 2003;
10(2):
129 - 140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ernst, S. J. Grant, E. D. London, C. S. Contoreggi, A. S. Kimes, and L. Spurgeon
Decision Making in Adolescents With Behavior Disorders and Adults With Substance Abuse
Am J Psychiatry,
January 1, 2003;
160(1):
33 - 40.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Elliott, J. L. Newman, O. A. Longe, and J. F. W. Deakin
Differential Response Patterns in the Striatum and Orbitofrontal Cortex to Financial Reward in Humans: A Parametric Functional Magnetic Resonance Imaging Study
J. Neurosci.,
January 1, 2003;
23(1):
303 - 307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Brody, M. A. Mandelkern, E. D. London, A. R. Childress, G. S. Lee, R. G. Bota, M. L. Ho, S. Saxena, L. R. Baxter Jr, D. Madsen, et al.
Brain Metabolic Changes During Cigarette Craving
Arch Gen Psychiatry,
December 1, 2002;
59(12):
1162 - 1172.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Layton and R. Krikorian
Memory Mechanisms in Posttraumatic Stress Disorder
J Neuropsychiatry Clin Neurosci,
August 1, 2002;
14(3):
254 - 261.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Best, J. M. Williams, and E. F. Coccaro
Evidence for a dysfunctional prefrontal circuit in patients with an impulsive aggressive disorder
PNAS,
June 11, 2002;
99(12):
8448 - 8453.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Shuren and J. Grafman
The Neurology of Reasoning
Arch Neurol,
June 1, 2002;
59(6):
916 - 919.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Frohman, T. C. Frohman, and A. M. Moreault
Acquired Sexual Paraphilia in Patients With Multiple Sclerosis
Arch Neurol,
June 1, 2002;
59(6):
1006 - 1010.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. D. Critchley
Book Review: Electrodermal Responses: What Happens in the Brain
Neuroscientist,
April 1, 2002;
8(2):
132 - 142.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. A. Parkinson, H. S. Crofts, M. McGuigan, D. L. Tomic, B. J. Everitt, and A. C. Roberts
The Role of the Primate Amygdala in Conditioned Reinforcement
J. Neurosci.,
October 1, 2001;
21(19):
7770 - 7780.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Morris and R. J. Dolan
Involvement of Human Amygdala and Orbitofrontal Cortex in Hunger-Enhanced Memory for Food Stimuli
J. Neurosci.,
July 15, 2001;
21(14):
5304 - 5310.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schoenbaum and B. Setlow
Integrating Orbitofrontal Cortex into Prefrontal Theory: Common Processing Themes across Species and Subdivisions
Learn. Mem.,
May 1, 2001;
8(3):
134 - 147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Davidson
The neural circuitry of emotion and affective style: prefrontal cortex and amygdala contributions
Social Science Information,
March 1, 2001;
40(1):
11 - 37.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. R. Savage, T. Deckersbach, S. Heckers, A. D. Wagner, D. L. Schacter, N. M. Alpert, A. J. Fischman, and S. L. Rauch
Prefrontal regions supporting spontaneous and directed application of verbal learning strategies: Evidence from PET
Brain,
January 1, 2001;
124(1):
219 - 231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bechara, D. Tranel, and H. Damasio
Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions
Brain,
November 1, 2000;
123(11):
2189 - 2202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kubota, W. Sato, T. Murai, M. Toichi, A. Ikeda, and A. Sengoku
Emotional Cognition without Awareness after Unilateral Temporal Lobectomy in Humans
J. Neurosci.,
October 1, 2000;
20(19):
RC97 - RC97.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Elliott, K. J. Friston, and R. J. Dolan
Dissociable Neural Responses in Human Reward Systems
J. Neurosci.,
August 15, 2000;
20(16):
6159 - 6165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Quirk, G. K. Russo, J. L. Barron, and K. Lebron
The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear
J. Neurosci.,
August 15, 2000;
20(16):
6225 - 6231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. Baxter, A. Parker, C. C. C. Lindner, A. D. Izquierdo, and E. A. Murray
Control of Response Selection by Reinforcer Value Requires Interaction of Amygdala and Orbital Prefrontal Cortex
J. Neurosci.,
June 1, 2000;
20(11):
4311 - 4319.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. D. Critchley, R. Elliott, C. J. Mathias, and R. J. Dolan
Neural Activity Relating to Generation and Representation of Galvanic Skin Conductance Responses: A Functional Magnetic Resonance Imaging Study
J. Neurosci.,
April 15, 2000;
20(8):
3033 - 3040.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bechara, H. Damasio, and A. R. Damasio
Emotion, Decision Making and the Orbitofrontal Cortex
Cereb Cortex,
March 1, 2000;
10(3):
295 - 307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. D. London, M. Ernst, S. Grant, K. Bonson, and A. Weinstein
Orbitofrontal Cortex and Human Drug Abuse: Functional Imaging
Cereb Cortex,
March 1, 2000;
10(3):
334 - 342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. N. Cardinal, D. R. Pennicott, C. L. Sugathapala, T. W. Robbins, B. J. Everitt, and B. J. Everitt
Impulsive Choice Induced in Rats by Lesions of the Nucleus Accumbens Core
Science,
June 29, 2001;
292(5526):
2499 - 2501.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
