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The Journal of Neuroscience, January 1, 1998, 18(1):428-437
Dissociation Of Working Memory from Decision Making within the
Human Prefrontal Cortex
Antoine
Bechara1, 2,
Hanna
Damasio1, 3,
Daniel
Tranel1, and
Steven W.
Anderson1
1 Department of Neurology, Division of Behavioral
Neurology and Cognitive Neuroscience, and 2 Department of
Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa
City, Iowa, 52242, and 3 The Salk Institute of Biological
Studies, La Jolla, California, 92186
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ABSTRACT |
We tested the hypothesis that cognitive functions related to
working memory (assessed with delay tasks) are distinct from those
related to decision making (assessed with a gambling task), and that
working memory and decision making depend in part on separate
anatomical substrates. Normal controls (n = 21),
subjects with lesions in the ventromedial (VM) (n = 9) or dorsolateral/high mesial (DL/M) prefrontal cortices
(n = 10), performed on (1) modified delay tasks
that assess working memory and (2) a gambling task designed to measure
decision making. VM subjects with more anterior lesions
(n = 4) performed defectively on the gambling but
not the delay task. VM subjects with more posterior lesions
(n = 5) were impaired on both tasks.
Right DL/M subjects were impaired on the delay task but
not the gambling task. Left DL/M subjects were not
impaired on either task. The findings reveal a cognitive and anatomic
double dissociation between deficits in decision making (anterior VM)
and working memory (right DL/M). This presents the first direct
evidence of such effects in humans using the lesion method and
underscores the special importance of the VM prefrontal region in
decision making, independent of a direct role in working memory.
Key words:
decision making; working memory; dorsolateral prefrontal
cortex; orbitofrontal cortex; delay tasks; gambling tasks; disinhibition; control of interference
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INTRODUCTION |
Studies in nonhuman primates have
shown that lesions of the dorsolateral (DL) prefrontal cortex give rise
to severe impairments in working memory (Goldman-Rakic, 1987 , 1992).
This has been found in several experiments using a variety of delay
task procedures. All of them have one feature in common: a temporal gap
between a stimulus and a response, i.e., a need to maintain in
temporary memory stores a particular stimulus. Such findings are
consistent with findings in humans with DL lesions who exhibit
impairments in working memory, as defined by Baddeley (1992). They are
also consistent with functional neuroimaging studies in humans
supporting a role for the DL cortex in working memory (Jonides et al.,
1993; Petrides et al., 1993; McCarthy et al., 1994; D'Esposito et al., 1995a; Smith et al., 1995; Cohen et al., 1997; Courtney et al., 1997).
Although these studies suggest that the DL cortex is necessary for
working memory, the question of whether the DL cortex is necessary for
decision making, defined as the ability to select an advantageous response from among an array of available options (Damasio et al.,
1991; Damasio, 1994), has not been addressed.
On the other hand, studies in humans with bilateral damage of the
ventromedial (VM) prefrontal cortex show that VM subjects develop
severe impairments in decision making, as defined above (Eslinger and
Damasio, 1984; Grafman et al., 1990; Damasio et al., 1991; Shallice and
Burgess, 1991; Damasio, 1994), but their working memory appears normal
on standard clinical neuropsychology tests (Grafman et al., 1990;
Anderson et al., 1991; Tranel et al., 1994). Using an experimental
paradigm, the gambling task, which simulates real-life situations in
the way it factors uncertainty, reward, and punishment (Bechara et al.,
1994), VM subjects are unable to choose advantageously during the
performance of this task, despite the correct knowledge of which are
the good and bad decks in the task (Bechara et al., 1994; Bechara et
al., 1996; Bechara et al., 1997). These studies suggest that the VM
cortex is necessary for decision making. It is less clear whether the VM cortex is necessary for working memory, in view of the sensitivity of tasks used so far.
The primary objective of this investigation was to determine whether
defects in decision making and working memory could be dissociated. To
achieve this objective, we relied on the use of delayed task procedures
to measure working memory, and on the gambling task to measure decision
making. Several studies have established that the use of a variety of
delay task procedures provides a valid measure of working memory
(Goldman-Rakic, 1987, 1992; Jonides et al., 1993; Petrides et al.,
1993; McCarthy et al., 1994; D'Esposito et al., 1995a; Smith et al.,
1995; Swartz et al., 1995; Fuster, 1996). Other studies have
established that the gambling task also provides a valid measure of
decision making (Bechara et al., 1994; Bechara et al., 1996; Bechara et
al., 1997). Our rationale for the idea that working memory and decision
making are dissociable comes from (1) the observations that VM subjects suffer from impairments in decision making but preserve a normal level
of memory and intellect (Eslinger and Damasio, 1985; Damasio et al.,
1990; Damasio, 1996); on the other hand, although some DL subjects
complain of memory impairments, they do not appear to suffer from
impairments in decision making, as judged from their behavior in real
life; and (2) the theoretical argument that working memory provides the
mechanism by which representations of various options and scenarios are
held on-line over a period (Fuster, 1990; Baddeley, 1992;
Goldman-Rakic, 1992). This mechanism, however, does not explain how one
of those representations gets selected for action. Therefore, it has
been proposed that another mechanism marks these various options and
scenarios, which are temporarily held in working memory, with positive
or negative values, and then from among this array of available options
the most advantageous option is selected for action (Damasio et al., 1991; Damasio, 1994; Damasio, 1996). This mechanism, which underlies the selection of good from bad options, is what we refer to as decision
making (Bechara et al., 1994; Bechara et al., 1996; Bechara et al.,
1997). Given the role of the DL cortex in working memory (Fuster,
1996), versus the VM cortex and its links with the limbic system and
the processing of reward and punishment (Damasio, 1996), we
hypothesized that VM prefrontal structures are necessary for decision
making but not for working memory, whereas DL prefrontal structures are
necessary for working memory but not for decision making. Thus, we
predicted that VM subjects would show impaired decision making, as
assessed with the gambling task, but normal working memory, as assessed
with a variety of delay tasks. On the other hand, we predicted that
subjects with DL lesions would show impaired working memory but normal
decision making, as assessed with the same tasks. We tested these
predictions in a population of neurological patients with bilateral
focal damage in the VM prefrontal cortices and inpatients with damage
in the right or left dorsolateral prefrontal cortices.
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MATERIALS AND METHODS |
Normal controls were recruited through local advertisement, and
they were paid for their participation. Subjects with frontal lobe
lesions (n = 19) were selected from the patient
registry of the University of Iowa Division of Behavioral Neurology and Cognitive Neuroscience. All frontal subjects had undergone basic neuropsychological and neuroanatomical characterization according to
the standard protocols of the Benton Neuropsychology Laboratory (Tranel, 1996) and the Laboratory of Neuroimaging and Human
Neuroanatomy (Damasio and Damasio, 1989; Damasio and Frank, 1992;
Damasio, 1995).
All subjects provided informed consent. None of the subjects in this
study had a history of mental retardation, learning disability, psychiatric disorder, substance abuse, or systemic disease that may
affect the CNS.
The selection of subjects with brain lesions conformed to the following
criteria: (1) a stable and chronic lesion (at least 3 months after
onset), (2) bilateral involvement of orbital and ventromedial cortices,
and (3) unilateral involvement of prefrontal and premotor cortices.
Because subjects with lesions restricted to the DL prefrontal cortices
are relatively rare, we decided to include also subjects with high
mesial lesions. Thus, subjects with unilateral DL and/or high mesial
lesions were included in a group that we will designate from here on as
the DL/mesial (DL/M) group.
Characteristics of the control and brain-damaged
subject groups
The control group included 14 women and 7 men (n = 21) with an age range from 24 to 68 years and 7-19 years of
education. The brain-damaged groups included nine VM subjects (three
women and six men), four right DL/M subjects (all men), and six left DL/M subjects (one woman and five men). The subjects in all frontal lobe groups had an age range from 30 to 68 years and 8-18 years of
education. The neuropsychological profiles for subjects with brain
damage are shown in Table 1.
Anatomical analysis
The description of extent of brain damage was done on the basis
of lesion overlap among brain-damaged subjects in each group. All
lesions of individual subjects were transferred onto a normal reference
brain using the MAP-3 technique (Frank et al., 1997). In brief, the
method entails the following: (1) a normal three-dimensional brain that
is sliced in such a way that the slices match the slices of the
magnetic resonance or computed tomographic scan of the subject with the
brain lesion; a match between the slices of the two brains is thus
created; (2) the contour of the lesion is transposed manually onto the
slices of the normal brain, taking into consideration the relation of
the lesion and the identified pertinent anatomical landmarks; and (3)
for each lesion the set of contours constitutes an "object" that
can be co-rendered with the normal brain. The objects corresponding to
the different lesions in the group can intersect in space and thus can
yield a maximal overlap relative to both surface and depth extension of
damage. The number of subjects contributing to the overlap is known in
each case.
Characteristics of the experimental tasks
Controls and brain-damaged subjects were tested on two sets of
behavioral tasks: (1) the gambling task to test decision
making, and (2) the delayed response and delayed nonmatching to
sample tasks (with repeated stimuli) to test working
memory.
The rationale for using two types of delay tasks was based on studies
in nonhuman primates showing that different areas of the dorsolateral
frontal cortex are associated with different domains of working memory:
the inferior areas have been associated with object memory, whereas the
superior areas have been associated with spatial memory (Goldman-Rakic,
1987, 1992; Wilson et al., 1993). Similar dissociations were found
recently in humans (Courtney et al., 1996). The delayed response tasks
have been designed to tax the spatial (where) domain of
working memory, whereas the delayed nonmatching to sample tasks are
supposed to tax the object (what) domain of working memory
(Fuster, 1990; Wilson et al., 1993). Because our DL/M lesions were not
restricted to the inferior or superior regions, and the lesions spanned
a wide area of DL cortices, we used both types of delayed tasks,
because we anticipated that both domains of working memory (spatial and
object) may be affected. In other words, we are not trying to sort out
differences between different types of working memory but, rather, to
cover a range of working memory with one task.
Testing of decision making. Decision making was assessed by
a gambling task described in more detail previously (Bechara et al.,
1994). In brief, this task entails the following.
Subjects sit in front of four decks of cards and are given a $2000 loan
of play money (a set of facsimile U.S. bills); the goal is to win as
much money as possible. The subjects are told that the game requires a
long series of card selections, one card at a time, from any of the
four decks, until they are told to stop. After turning each
card, the subject receives some money (the amount is only announced
after the turning and varies with the deck). After turning
some cards, the subject is both given money
and asked to pay a penalty (again the amounts are only
announced after the card is turned and vary with the deck and the
position of the card in the deck according to a schedule unknown to the subjects). Turning 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), allowing a final gain. Thus,
decks A and B are "disadvantageous," whereas decks C and D are
"advantageous." Scores are the total numbers of cards selected from
decks A and B (bad decks) versus the total numbers of cards selected
from decks C and D (good decks).
Testing of working memory. Delay tasks that are used in
nonhuman primates are too simple for use with humans. Therefore, we introduced a distractor during the delay between the cue and the response. The purpose of the distractor was to interfere with the
ability of the subject to rehearse the position or the color of the
cues during the delay and to increase the demands of the tasks on
working memory.
Delayed response experiment
The subject sat in front of a computer screen on which four
cards appeared for 2 sec. Two of the cards were face down, and the
other two were face up showing red and/or black colors. The two face-up
cards were randomly positioned among the four cards, and they also
randomly changed from one trial to the next. The subjects were asked to
pay attention to the four cards before they disappeared from the
screen. Initially, the cards disappeared for one second and then
reappeared, but this time all of the cards were face down. The subjects
were told to select two of the four cards. The subjects were expected
to discover, by themselves, that the two cards that were first face up
were the correct ones to select. When a subject selected the two
correct cards, a message appeared on the screen indicating that the
subject had made the correct choice, and a $100 bill was added to a
pile of money appearing at the bottom left corner of the computer
screen. If the subject selected one or two incorrect cards, the message
indicated that the subject had made an incorrect choice, and $100 was
deducted from the money pile.
After discovering the rules and reaching a learning criterion of five
consecutive correct choices, the time delay between the appearance and
reappearance of the cards began to alternate between 10, 30, or 60 sec
in a random manner. During the delay, the subject had to read aloud a
series of semantically meaningless sentences. Subjects were told that
the goal in this game was to win as much money as possible. The task
consisted of completing 15 trials in each of the 10, 30, and 60 sec
delay categories. Scores were calculated as the percent correct choices
made by the subject at the 10, 30, and 60 sec delays. Impaired
performance on the delayed response task was defined as achieving a
correct score of  80% at the 60 sec delay, a cutoff score below which no normal control ever performed (see Results).
Delayed nonmatching to sample experiment
In this experiment, the task was similar to the delayed response
task, except that only one card appeared initially on the computer
screen for 2 sec. The card was face up and was either red or black. The
red or black color of the card randomly changed from one trial to the
next. The card disappeared for one second, and then four cards appeared
on the screen. All the cards were face up; two of them were red, and
two were black. The positions of the red and black cards were random.
The subjects were expected to discover, by themselves, that selecting
the two cards that were opposite in color (nonmatching) to the initial
sample card was the correct response. After discovering the rules and
reaching a learning criterion of five consecutive correct responses,
the time delay between the appearance of the sample card and the
appearance of the two matching and two nonmatching cards began to
alternate among 10, 30, or 60 sec in a random manner. During the delay, the subject was distracted as in the previous experiment. The task
consisted of completing 15 trials in each of the 10, 30, and 60 sec
delay categories. Scores were calculated as the percent correct choices
made by the subject at the 10, 30, and 60 sec delays. Impaired
performance on the delayed nonmatching to sample task was defined as
achieving a correct score of 80% at the 60 sec delay, a cutoff score
below which no normal control ever performed (see Results).
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RESULTS |
Lesion description in brain-damaged groups
The overlap maps of lesions for the three groups of brain-damaged
subjects are shown in Figure 1. The
lesions in the VM group (Fig. 1A) showed a maximum
overlap in the ventral and low mesial sectors of the frontal lobe, in
both the right and left hemispheres. Some of the lesions also extended
to involve the frontopolar region and the most anterior sectors of the
dorsolateral regions. The DL/M lesions (six on the left and four on the
right) (Fig. 1B) covered the dorsolateral sector of
the frontal lobes but did not reach the polar region. They also
involved the high medial sectors of the frontal lobes above the level
of the body of the corpus callosum. They did not reach the low mesial
sector below this level of the callosum. In the right hemisphere, the
lesions also extended into the orbital sector but stayed in the lateral
half, not involving the mesial orbital sector.
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Figure 1.
Overlap of lesions in the three groups of
brain-damaged subjects. A, Bilateral VM lesions.
B, Right and left DL/M lesions. C, Color
bar showing the color code corresponding to number of overlap of
lesions.
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Task results in normal controls
Normal controls selected an average of 62 cards from the good
decks versus 38 cards from the bad decks. Based on unpublished normative data, we set a cutoff point at which the selection of >50
cards from the bad decks (i.e., <50 cards from the good decks) was
classified as defective.
Normal controls achieved a high percent correct score on both the
delayed response and delayed nonmatching to sample tasks. In our
comparisons (below), we used the percent correct responses obtained at
the 60 sec delay as our dependent variable, because in our task, this
is the time when demand for working memory was the highest. The
performance of normal controls at the 60 sec delay was ~95% correct
for the delayed response task and 90% correct for the delayed
nonmatching to sample task. No normal control achieved a score of
<80% correct. Thus scores of <80% were classified as defective.
Task results in brain-damaged subjects
Gambling task
Nine out of nine subjects in the VM group selected >50 cards
from the bad decks; i.e., all were impaired on the gambling
task (Fig. 2).
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Figure 2.
Comparison of the performance of the three
brain-damaged groups and the normals. Each graph represents mean ± SEM of the percent correct responses, or total number of cards
selected from the good versus the bad decks, that were made by normal
controls (n = 21), by subjects with bilateral
orbital and VM frontal lobe lesions (n = 9), by
subjects with lesions in the right DL/M sector of the prefrontal cortex
(n = 4), or by subjects with lesions in the left
DL/M sector of the prefrontal cortex (n = 6). We
note that every participant in the delayed response and delayed
nonmatching to sample tasks reached a 100% learning criterion at the 0 sec delay before the task could proceed to the 10, 30, or 60 sec
delays.
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Ten of 10 subjects in the the DL/M group selected >50 cards from
the good decks; i.e., all were normal on the gambling task. When
the gambling task scores from right DL/M subjects and the scores from
left DL/M subjects were analyzed separately, there were no statistical
differences in the number of cards selected from the good or bad decks
by right DL/M subjects compared with normals (Mann-Whitney
U test Z =  0.92; p > 0.1)
or by left DL/M subjects compared with normals (Mann-Whitney
U test Z = 0.94; p > 0.1). Nonetheless, there was some difference in the level of the normal
performance of the right DL/M group relative to the left. Although the
average performance of the left DL/M subjects was just as good, or even
better, than that of normal controls, the average performance of right
DL/M subjects was in the low normal range (Fig. 2).
Delay tasks
As a group, subjects with VM lesions were mildly impaired on the
delayed response task and were borderline on the delayed nonmatching to
sample task (Fig. 2). However, it was interesting to see that the
performance on these tasks was not uniformly abnormal or borderline. In
fact, the group could be subdivided into two subgroups, in which five
of the VM subjects had impaired performance on both delay tasks,
whereas four of the subjects had normal performance on both delay
tasks.
In the four subjects with VM lesions and normal delay performance, the
scores were indistinguishable from controls, and if anything, their
scores were even better than normal controls (Fig. 3). In the other five subjects (VM
lesions and abnormal delay task performance), the degrees of impairment
were similar on both delay tasks (Fig. 3). At the 60 sec delay, these
subjects had significantly lower scores than normal controls
(Mann-Whitney U tests revealed Z = 3.11;
p < 0.01 for delayed response, and Z = 3.06; p < 0.01 for delayed nonmatching to sample).
Because Figure 3 indicates that the degree of impairment increased as a
function of the length of the delay, the results suggest that the
impairment was related to memory.
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Figure 3.
Mean ± SEM of the percent correct responses,
or total number of cards selected from the good versus the bad decks,
that were made by normal controls (n = 21) and by
subjects with bilateral orbital and VM frontal lobe lesions who were
divided into two groups based on their performance on the delayed
response and delayed nonmatching to sample tasks: group 1 (abnormal
gambling and abnormal delay) (n = 5) and group 2 (abnormal gambling and normal delay) (n = 4).
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In the DL/M group, three subjects with right hemisphere lesions showed
abnormal performance on both delay tasks. One subject (with a lesion
restricted to the inferior area of the dorsolateral sector on the
right) showed selective impairment on the delayed nonmatching to sample
but not on the delayed response task. The six subjects with left
hemisphere lesions had normal performances on both delay tasks (Fig.
2).
The degree of impairment on the delayed response task in the right DL/M
subjects was less severe than that of the delayed nonmatching to sample
because of the one subject who did not show a deficit on the delayed
response task. At the 60 sec delay, these subjects achieved
significantly lower scores than normal controls (Mann-Whitney
U tests revealed Z = 2.2;
p < 0.05 for delayed response, and Z = 2.8; p < 0.05 for delayed nonmatching to sample). Because the figure indicates that the degree of impairment appeared to
increase as the time of delay got longer, the results suggest a
memory-related impairment. The finding of normal performance on the
delayed response task and abnormal performance on the delayed nonmatching to sample task in the one subject whose lesion was restricted to the inferior sector of the dorsolateral sector is consistent with several previous studies (Goldman-Rakic, 1987, 1992;
Wilson et al., 1993; Courtney et al., 1996).
The left DL/M subjects appeared to have lower scores than normals at
the 30 and 60 sec delays, but these differences were not statistically
significant.
Further anatomical investigation of the VM subjects
Because of our finding of a split in the delay task performance in
the VM group, five subjects with abnormal delay task performance and
four subjects with normal performance, we decided to analyze these two
subgroups separately: group 1, those with both abnormal gambling task performance and abnormal delay task performance; and
group 2, those with abnormal gambling task performance but normal delay task performance (Fig. 3).
This split in performance of VM subjects on the delay tasks but not on
the gambling task was intriguing. We suspected an anatomical reason
underlying this separation. Therefore, we looked at the overlap of
lesions in these two groups separately. In group 1 (abnormal gambling
and abnormal delay), all subjects had lesions that extended
posteriorly, possibly involving the basal forebrain region. However, in
group 2 (abnormal gambling and normal delay), the lesions were more
anterior and probably did not involve the basal forebrain region (Fig.
4). We purposefully state that the lesions "probably" involved (or did not involve) the basal
forebrain region; because of the nature of many of these lesions, their surgical treatment (clipping of ruptured aneurysms), and the
unavoidable artifact they induce, a clear-cut decision of "yes" or
"no" involvement is not possible.
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Figure 4.
Separate mapping of VM lesions for group 1 (A) and group 2 (B)
subjects. The maximal overlap of subjects in A is seen
spanning the whole extent of the mesial orbital surface of the frontal lobe. It reaches the most posterior sector (coronal slices
3, 4) where basal forebrain
structures are found. However, in B the maximal overlap
is mostly anterior, extending only to slices 1 and
2. Slices 3 and 4 do not
show any lesion. Coronal sections are arranged according to
radiological convention, i.e., right is left, and vice
versa.
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Further statistical analyses
When the gambling task scores from subjects classified as group 1 and the gambling scores from subjects classified as group 2 were
analyzed separately, there was no difference in the severity of
impairment on the gambling task. We conducted a two-way ANOVA comparing
the number of cards selected by normal controls and group 1 and group 2 subjects (a between-group comparison). The comparison was made with
regard to the number of cards selected from the good decks versus the
bad decks (a within-group comparison). The analysis revealed a
significant interaction of group with decks
(F(2,15) = 13.3; p < 0.001),
reflecting the fact that both VM groups selected more cards from the
bad decks, whereas the controls selected more cards from the good
decks. Post hoc Newman-Kuels tests revealed that the
numbers of cards selected from the good decks by normal controls were
signifcantly higher than those selected from the bad decks. By
contrast, the numbers of cards selected from the bad decks by both VM
groups were significantly higher than those selected from the good
decks (p < 0.01). It is worth mentioning that
the performance of group 1 (abnormal gambling and abnormal delay)
subjects appeared worse than that of group 2 subjects (i.e., they
selected more bad cards and less good cards). However, this difference
was not statistically significant (Fig. 3).
The group 2 subjects had abnormal gambling (i.e., selected fewer cards
from the good decks) but normal delay task scores. By contrast, the
right DL/M subjects had normal gambling but abnormal delay task scores
(Fig. 5). To confirm statistically the
reliability of the finding of a double dissociation in the deficits
associated with anterior VM and right DL/M lesions, we conducted the
following analysis. The scores from the two delay tasks at the 60 sec
delay were merged into a single score by taking an average of the two. The two scores reflecting the number of cards from the good or bad
decks on the gambling task were also merged into a single score equal
to the number of cards from the good decks minus the number of cards
from the bad decks. Thus, a positive number reflects an advantageous
performance, whereas a negative number reflects a disadvantageous
performance. A two-way ANOVA comparing the group 2 (anterior VM) and
right DL/M groups (between-group comparison) on the scores from the
delay versus the gambling tasks (within-group comparison) revealed a
significant interaction of groups with tasks
(F(1,6) = 35.0; p < 0.001),
reflecting the fact that the group 2 (anterior VM) subjects had high
delay task scores (i.e., normal performance) and negative gambling
scores (i.e., abnormal performance), whereas the right DL/M subjects
had low delay task scores (abnormal) and positive gambling task scores
(normal). Post hoc Newman-Kuels tests confirmed that the
delay task scores from group 2 (anterior VM) were significantly higher
than those from right DL/M, whereas the gambling scores were
signifcantly lower (p < 0.01).
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Figure 5.
Mean ± SEM of the average of percent correct
responses from the two delay tasks, or the total number of cards
selected from the good decks, that were made by VM subjects with more
anterior lesions (group 2), and by subjects with right DL/M
lesions.
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DISCUSSION |
Our initial hypothesis was that the VM prefrontal structures would
be necessary for decision making but not for working memory, whereas
the DL prefrontal structures would be necessary for working memory but
not for decision making. Our results show that, in fact, all subjects
with VM lesions are impaired on the gambling task, whereas only a
subset of these subjects, those with the most anteriorly placed
lesions, presumably sparing the basal forebrain structures, are normal
on the delay tasks. As predicted, subjects with right DL/M lesions were
impaired on the delay tasks but not on the gambling task. These results
suggest a double dissociation between impairments in these two tasks,
that is, between decision making on the one hand and working memory for
the spatial and object domains on the other.
Our initial prediction that we would find a complete double
dissociation between decision making and working memory relative to the
VM and DL sectors of the prefrontal cortex, however, has to be revised.
The results suggest that a working memory impairment influences, to
some extent, decision making, given that (1) the subjects in the
right DL/M group performed at a low normal level in the
gambling task; and that (2) the VM subjects with posterior lesions and
abnormal performance on the delay tasks showed the worst performance on
the gambling task. We interpret these findings as evidence that working
memory and decision making may be asymmetrically dependent. Working
memory is not dependent on the intactness of decision making; i.e.,
subjects can have normal working memory in the presence or absence of
deficits in decision making. On the other hand, decision making seems
to be influenced by the intactness or impairment of working memory;
i.e., the subject's decision making is affected by having an abnormal
working memory.
Subjects with left DL/M lesions were normal on both the
gambling and delay tasks. The normal gambling task performance had been
predicted, and the absence of a working memory impairment is not
surprising, because, during the delay, the verbal memorization of cues
was probably avoided by the interference procedure, thus rendering the
task primarily nonverbal. This is consistent with several functional
neuroimaging studies in humans that showed higher activation in the
right dorsolateral frontal cortex, relative to the left, during the
performance of similar delay tasks (Jonides et al., 1993; Petrides et
al., 1993; McCarthy et al., 1994; D'Esposito et al., 1995a,b; Smith et
al., 1995; Swartz et al., 1995).
It could be argued that the reason for the separation of the two VM
groups is related to the size of the lesion, rather than to the
placement of the lesion. This, however, is not the case. As can be seen
in Figure 6, EVR318, who has a large
bilateral frontal lesion, has abnormal performance in the gambling task but normal performance in the delay task. On the other hand, VY500 has
a smaller, more limited lesion in the posterior orbital and mesial
sector of the frontal lobe and is impaired on both tasks. A large
dorsolateral lesion in the right frontal lobe, as in case AH1331, which
even involves the lateral part of the orbital sector but spares its
medial portion, has normal performance in the gambling task, whereas
the delayed response is abnormal. Yet DV1589, with a small lesion in
the mesial orbital sector, mostly on the right, shy of the basal
forebrain region and much smaller than the lesion of AH1331, does show
a deficit in the gambling task but not the delay task. In sum, it is
the placement of the lesion, rather than its size, that accounts for
the observed deficits.
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|
Figure 6.
Examples of mapped individual cases from the VM
and DL/M groups demonstrating that placement of the lesion, rather than
the size of the lesion, is the crucial variable in producing the
various combinations of deficits (see Discussion for detail).
|
|
We draw support for our conclusion that subjects with right DL/M
lesions have a working memory deficit in spatial and object domains
from the evidence of a large body of studies demonstrating that
structures within the dorsolateral prefrontal cortices are implicated
in working memory (Goldman-Rakic, 1987, 1992; Jonides et al., 1993;
Petrides et al., 1993; McCarthy et al., 1994; D'Esposito et al.,
1995a; Smith et al., 1995; Swartz et al., 1995; Fuster, 1996). We also
conclude that subjects with posterior VM lesions involving the basal
forebrain region might have had abnormal performance on the delay tasks
because of an impairment of working memory in those domains. That such
subjects have memory defects had been established previously (Damasio
et al., 1985; Markowitsh and Pritzel, 1985), and it seems plausible
that the basal forebrain region may serve as a parallel system to the
dorsolateral prefrontal cortex for working memory (Swartz et al.,
1995), given the close anatomical links between the two regions (Devito
and Smith, 1964). In the posterior VM group, the memory deficit might
have had an additional effect on their decision making capacity and
contributed to the fact that, as a group, these subjects had the worst
performance in the gambling task.
Our findings of a separation of VM lesions into two distinct groups is
important and may explain the equivocal results of earlier lesion
studies in humans on the effects of VM damage on the performance of
delay tasks (Ghent et al., 1962; Chorover and Cole, 1966; Freedman,
1986). It is likely that in these earlier studies some lesions may have
extended posteriorly and involved the basal forebrain region, whereas
others did not, thus resulting in a mixed group. Our results are also
compatible with findings of functional neuroimaging studies in humans
that did not reveal any activation within the anterior orbital and
ventromedial prefrontal cortices during the performance of a variety of
delay task procedures (Jonides et al., 1993; Petrides et al., 1993;
McCarthy et al., 1994; D'Esposito et al., 1995a; Smith et al., 1995;
Cohen et al., 1997; Courtney et al., 1997). In the only case in which
ventromedial frontal activation was observed, it was found in the
region closest to the basal forebrain (Swartz et al., 1995), a finding
that again is in agreement with our results presented here.
Still, other possible explanations for the defective performance on the
gambling task, which were not specifically tested in this study,
include impairments in response inhibition and selective attention.
Indeed, the VM prefrontal cortex is important for response inhibition
and attentional shifting in both animals (Mishkin, 1964; Fuster, 1991;
Dias et al., 1996) and humans (Diamond, 1990; Stuss et al., 1992).
Furthermore, in addition to impairments in working memory, studies in
nonhuman primates have shown that impaired delay task performance can
also result from impairments in selective attention (Heilman et al.,
1987; Rizzolatti and Camarda, 1987) and response inhibition (Mishkin,
1964; Fuster, 1991; Dias et al., 1996; Fuster, 1996). Because in our
gambling task the subjects were rewarded repeatedly before encountering
a loss when choosing cards from a bad deck, it might be argued that the
impaired performance of the VM subjects was caused by defective
response inhibition, i.e., the inability to suppress previously
rewarded responses and shifting attention to the good decks. However,
this explanation is inconsistent with several facts. (1) VM subjects with lesions restricted to the anterior sector (abnormal gambling and
normal delay) do not show any perseverative behavior and attentional deficit on conventional neuropsychological tests (Table 1). (2) When we
analyze the profile of performance of these anterior VM subjects on the
gambling task, we find that these subjects switch decks whenever they
receive punishment, just as normal controls do, although they return
more often to the decks that yield high immediate reward (the bad
decks). The switch away from the bad deck immediately after a
punishment does not indicate lack of inhibition of the natural tendency
to shift decks after a negative outcome (Bechara et al., 1994). (3)
Anterior VM subjects are not impaired on the delay tasks, which have
been considered sensitive to deficits in selective attention and
response inhibition as mentioned above. In short, we believe that these
facts strongly argue against impairments in response inhibition and
selective attention as an explanation for the impaired gambling task
performance. We may even go as far as to conclude that the ability to
select an advantageous response from among an array of response options is probably distinct from working memory, from response inhibition, and
from selective attention.
It is clear that the failure of VM subjects to choose advantageously
does not result from their failure to appreciate the value of each
deck, because VM subjects continue to choose disadvantageously, even
when they know which decks are good and which ones are bad (Bechara et
al., 1997). We considered three possibilities for why VM subjects
continue to prefer the bad decks over the good decks: (1)
hypersensitivity to reward, in which the prospect of a large immediate
gain outweighs any prospect of future loss; (2) insensitivity to
punishment, in which the prospect of a large loss cannot override any
prospect of gain; and (3) insensitivity to future consequences,
positive or negative, in which the immediate prospects override any
future prospects. Preliminary evidence (Anderson et al., 1996) suggests
that in most VM subjects, the decision-making impairment is linked to
insensitivity to future consequences, whatever they may be. Thus, the
VM subject appears oblivious to the future and guided by only immediate
prospects, positive or negative.
| |
FOOTNOTES |
Received Aug. 8, 1997; revised Oct. 20, 1997; accepted Oct. 23, 1997.
This work was supported by National Institute of Neurological Diseases
and Stroke Grant PO1 NS19632, the James S. McDonnell Foundation, and
the Centennial Medical Research Council (Canada). We are indebted to
the valuable contribution of Jon Spradling for computerizing the delay
tasks used in this study.
Correspondence should be addressed to Antoine Bechara, Department of
Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA
52242.
| |
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Top
Abstract
Introduction
