 |
 Previous Article | Next Article 
The Journal of Neuroscience, August 1, 1999, 19(15):6610-6614
Orbitofrontal Cortex and Representation of Incentive Value in
Associative Learning
Michela
Gallagher,
Robert W.
McMahan, and
Geoffrey
Schoenbaum
Department of Psychology, Johns Hopkins University, Baltimore,
Maryland 21218
 |
ABSTRACT |
Clinical evidence indicates that damage to ventromedial prefrontal
cortex disrupts goal-directed actions that are guided by motivational
and emotional factors. As a consequence, patients with such damage
characteristically engage in maladaptive behaviors. Other research has
shown that neurons in the corresponding orbital region of prefrontal
cortex in laboratory animals encode information regarding the incentive
properties of goals or expected events. The present study investigates
the effect of neurotoxic orbitofrontal cortex (OFC) lesions in
the rat on responses that are normally influenced by associations
between a conditioned stimulus (CS) and the incentive value of
reinforcement. Rats were first trained to associate a visual CS with
delivery of food pellets to a food cup. As a consequence of learning,
rats approached the food cup during the CS in anticipation of
reinforcement. In a second training phase, injection of LiCl followed
consumption of the food unconditioned stimulus (US) in the home cage, a
procedure used to alter the incentive value of the US. Subsequently,
rats were returned to the conditioning chamber, and their responding to
the CS in the absence of the food US was tested. Lesions of OFC did not
affect either the initial acquisition of a conditioned response to the light CS in the first training phase or taste aversion learning in the
second training phase. In the test for devaluation, however, OFC rats
exhibited no change in conditioned responding to the visual CS. This
outcome contrasts with the behavior of control rats; after devaluation
of the US a significant decrease occurred in approach to the food cup
during presentation of the CS. The results reveal an inability of a cue
to access representational information about the incentive value of
associated reinforcement after OFC damage.
Key words:
orbitofrontal; devaluation; goal neglect; prefrontal; associative learning; agranular insular
| |
INTRODUCTION |
Goal expectancy is an important
source of guidance in adaptive behavior. Recent findings suggest that a
deficit in this function contributes to the clinical presentation of
patients with damage to ventromedial prefrontal cortex. Clinical
accounts highlight poor judgment and socially inappropriate behavior
that can occur despite the patients' knowledge about social customs
and the likely outcome of their actions (Damasio, 1994 ; Rolls et al.,
1994; Bechara et al., 1997). A disturbance in motivational and
emotional factors that normally control behavior is often cited to
account for this profile, with patients variously described in
different contexts as passive or impulsive, distractible or
perserverative. Of particular interest is the notion that such patients
suffer from goal neglect, a concept that can encompass the seemingly
contradictory features of their behavior, e.g., both passive and
impulsive (Duncan et al., 1996). As in other forms of neglect, patients
are not incapable of awareness but fail to use available information to
guide their actions. The relevant information in goal neglect consists
of the incentive (or disincentive) properties of expected outcomes. This view of humans with prefrontal damage is consistent with other
evidence from recent studies examining the encoding properties of
prefrontal neurons in laboratory animals.
Neurons in the orbital region of the ventral prefrontal cortex encode
the motivational significance of cues and the incentive value of
expected outcomes (Thorpe et al., 1983; Schoenbaum and Eichenbaum,
1995; Critchley and Rolls, 1996; Rolls et al., 1996; Schoenbaum et al.,
1998, 1999; Lipton et al., 1999). Schoenbaum et al. (1998, 1999) found
that a substantial proportion of cells recorded in the orbital region
of the rat exhibited such properties during performance of an
odor-guided task. In particular, after rats had sampled an informative
odor cue, cells fired differentially depending on whether the outcome
was positive (sucrose) or negative (quinine) (Schoenbaum et al., 1998).
Evidence in that study indicated that this encoding was prospectively
related to the incentive value of the impending event.
Associations in which cues, responses, or contextual information are
linked to the incentive properties of outcomes provide an important
basis for expectancy in goal-directed behavior. To model this aspect of
associative learning, we used a task in which normal performance
depends on the ability of a conditioned stimulus (CS) to gain access to
the motivational properties of an upcoming unconditioned stimulus (US).
Our study used a procedure in which rats were first trained in standard
Pavlovian conditioning, using a light CS paired with food delivery.
After conditioned responses were established to the CS, rats received
the original US (food) in another setting in which it was paired with
an aversive event (injection of LiCl). This second phase of "US
devaluation" causes normal rats to subsequently decrease their
conditioned responses on initial re-exposure to the original CS.
Although the CS is absent during devaluation, its earlier association
with the US provides a basis for anticipating that event. If
orbitofrontal cortex (OFC) function is important for guiding behavior
through the use of such associations, then rats with OFC damage should be impaired in the CS test for devaluation.
| |
MATERIALS AND METHODS |
Subjects and surgical methods. Forty-three
male Long-Evans rats (Charles River Laboratories, Wilmington, MA) were
300-350 gm at the time of surgery. Anesthesia was induced by
isoflurane (Isovet; Mallinckrodt, Mundelein, IL) inhalation. After
induction of anesthesia, the rat was positioned in a Kopf stereotaxic
apparatus, and standard methods were used to make bilateral
microinjections of NMDA (Sigma, St. Louis, MO) at the following
coordinates according to the Paxinos and Watson (1986) atlas: 4.0 mm
anterior to bregma at both 2.2 and 3.7 mm lateral to midline and 4.2 mm
ventral from the skull surface. A second set of bilateral injections
was made at 3.0 mm anterior to bregma at both 3.2 and 4.2 mm lateral to the midline and 5.2 mm ventral to the skull surface. At each site, NMDA
(20 mg/ml) or the Krebs'-Ringer's solution phosphate vehicle was
delivered in a 0.1 µl vol over a 1 min interval, and the injector was
left in place for an additional 3 min. The incision was then sutured,
and rats were monitored post-operatively on a daily basis. One week
after surgery, rats were gradually reduced to 85% of ad
libitum weights by limiting access to food; water was always available. Rats were weighed and fed daily to maintain their 85% weights for the remainder of the experiment. Behavioral testing was
conducted during the light portion of the light/dark cycle between 7:00
A.M. and 2:00 P.M.
Apparatus and behavior. The testing apparatus consisted of
four individual chambers (Coulburn Instruments), each 27.9 × 25.4 × 30.5 cm. The food cup was recessed in the center of one
end wall 2 cm above the floor; a 4 W normally off light, which was the
source of the visual CS, was located 20 cm above the recessed food cup.
A 25 W red bulb placed 2.1 m from the chambers provided continuous
dim background illumination. A low-light television camera was placed
2.0 m from the experimental chambers. Videocassette recorders were
programmed to record behaviors that occurred during the 10 sec
intervals before, during, and after CS presentation.
The behavioral protocol was identical to that described in detail
elsewhere (Hatfield et al., 1996). Rats were first trained to eat from
the food cups. Ten deliveries of two 45 mg food pellets (which served
as the US) were given at random times within a single 64 min session.
Rats were then trained with Pavlovian pairings of a light CS (10 sec
duration) that terminated with the delivery of two food pellets, which
served as the US. Rats received five trials in each of eight daily
sessions. A random variable intertrial interval that averaged 8 min was
used. After the completion of this conditioning phase, the food pellet
US was devalued for half of the rats in each group by pairing with
injections of the toxin lithium chloride (LiCl); the remaining rats in
each group received unpaired presentations of the food pellet US and
LiCl. This procedure was conducted by placing 100 food pellets (450 mg)
in a glass dish in the animal's home cage for 10 min, then giving an
intraperitoneal injection of 0.3 M LiCl either immediately
or 6 hr later. The devaluation training trials were each separated by a
rest day. Finally, the devaluation test was conducted in the original
training apparatus. In a single session, each rat received five
presentations of the original CS without delivery of the food pellet US.
The measure of learning in appetitive conditioning and in the test for
devaluation was food cup behavior. Food cup behavior includes standing
motionless in front of the food cup, with the nose or head inserted
within the recessed area, and head-jerk behavior (short, rapid
horizontal, and/or vertical movements of the head). Behavioral
observations were made for each rat at 1.25 sec intervals from
videotapes, and paced by auditory signals recorded on the tapes. At
each observation, the observer recorded a single behavior. The index of
food cup behavior used was percentage total behavior, obtained by
dividing the frequency of that behavior in any observation interval by
the total number of observations made in that interval. Note that
because the number of observations was constant within each observation
interval, this measure is an absolute frequency measure, not a relative
one. Two observers scored the behavioral data reported in each
experiment; the observers were not aware of the rats' lesion
conditions when the data were scored. Food cup behavior is reported for
the final 5 sec of the 10 sec CS, before US delivery. A measure of food
devaluation in the conditioned taste aversion procedure was the amount
of food consumed in that phase of training.
Histology. After completion of behavioral testing, the rats
were deeply anesthetized with Nembutal (100 mg/kg) and were perfused transcardially with 0.9% saline followed by 10% formal saline. Brains
were removed and stored in 10% formalin for 1 week. The brains were
then sectioned (50 µm) in a cryostat, mounted on slides, and
Nissl-stained. Coronal sections were taken through the prefrontal region. Histological examination was performed with the aid of the
Swanson (1992) atlas using an Olympus (Tokyo, Japan) BH-2 microscope.
Data analysis. In the statistical analyses of the food cup
behavior, we used two-tailed, nonparametric statistics. Food
consumption data during devaluation training were analyzed using
two-way ANOVA. We adopted the 0.05 level of significance.
| |
RESULTS |
Bilateral lesions were accurately placed in 24 of the 26 rats that
received microinjections of excitotoxin. These rats had a marked loss
of neurons in OFC, including the medial, ventrolateral, and lateral
orbital regions and both dorsal and ventral agranular insular cortex.
Damage was confined to portions of OFC rostral to the genu of the
corpus callosum to avoid gustatory input to posterior agranular insular
cortex (Saper, 1982; Krushel and Van Der Kooy, 1988). On average,
lesions encompassed 75% of OFC bilaterally, ranging from 40 to 100%.
A photomicrograph of a lesion is shown in Figure
1 along with drawings depicting the range
of lesion size included in the experimental group. The largest lesions
(Fig. 1B) included some damage to claustrum and
frontal and parietal cortex dorsal to OFC (Fig.
1A,B). Damage outside of OFC was
typically unilateral, and rats with additional cortical damage did not
differ behaviorally from those that had no discernible loss of cells in
those regions.
View larger version (54K):
[in this window]
[in a new window]
|
Figure 1.
Photomicrographs and schematics showing the region
of OFC damage. A, Photomicrographs showing a coronal
section (anteroposterior, +2.7) from a control brain
(left panel) and a lesioned brain (right
panel). Note the neuronal loss, accompanied by gliosis,
in the ventrolateral and lateral orbital regions and in agranular
insular cortex in the lesioned brain. The region of cell loss ends at
the medial orbital area and extends dorsally somewhat into parietal
cortex. B, Drawings show the approximate extent and
range of the lesions that were included in the experimental group. The
boundaries of the minimal lesion (black fill) and
the maximal lesion (diagonal fill) are shown to
indicate of the range of damage. The approximate size of the lesion
(crossed fill) in a subject that is
representative of average lesion size is also shown [drawings adapted
from Swanson (1992)]. Damage was confined to portions of OFC rostral
to the genu of the corpus callosum to avoid gustatory input to
posterior agranular insular cortex (Saper, 1982; Krushel and Van Der
Kooy, 1988).
|
|
The acquisition of food cup responses during the initial conditioning
phase is shown in Figure 2. Irrespective
of lesion, all rats learned to approach the food cup during the CS that
signaled delivery of the food pellet before the devaluation procedure, as shown in the left panel. Indeed, statistical analysis
(Kruskal-Wallis) revealed no differences among the groups during this
phase of the experiment.
View larger version (17K):
[in this window]
[in a new window]
|
Figure 2.
Data are shown for each phase of the
behavioral experiment. Squares represent control groups,
and circles represent the lesioned groups. All groups
acquired conditioned food cup responses in phase 1, as shown in the
panel on the left. In phase 2, the groups represented by
filled symbols received unpaired food and LiCl;
open symbols represent groups that had paired
presentations of these events. As shown in the presentation of the
phase 3 devaluation test data, the control group for which food was
devalued (open bar on the left) reduced
conditioned responding relative to the unpaired control group
(solid bar). In contrast, the lesioned groups exhibited
conditioned responses that did not differ as a function of devaluation.
See Materials and Methods for details of statistical
analyses.
|
|
As a result of US-LiCl pairings, both control and OFC lesion groups
formed an aversion to food pellets and would not consume them during
consumption tests (Fig. 2, middle panel). Note
that control rats and rats with OFC lesions that received unpaired food-LiCl continued to consume food pellets, as expected. ANOVAs for
each training condition, however, indicated no significant differences
between the control and lesioned groups
(F(1,23) = 2.05; p > 0.1 for paired and F(1,20) = 0.015;
p > 0.1 for unpaired).
The data of primary interest were obtained during the subsequent test
of responding to the light CS in the absence of the food US. The
control group that underwent devaluation training showed a spontaneous
drop in CRs relative to the control group for which the US was not
devalued (control groups, U = 22; p < 0.01). No effect of devaluation, however, was apparent in comparison of
the OFC-lesioned groups (U = 62.5; p = 0.60). In addition, the CRs for the OFC devalued group did not differ
from the unpaired control group (U = 59;
p = 0.94) but differed significantly from the devalued
control group (U = 38; p < 0.05).
| |
DISCUSSION |
Responding to a CS can be sensitive to post-training alterations
in the value of a US (Holland and Straub, 1979, Colwill, 1993). This
phenomenon is consistent with the view that performance of conditioned
responses (CRs) is mediated, at least in part, by access to properties
of an associated US; when the US is not present, the CS activates some
representation of the reinforcement. In the current study the behavior
of intact rats was influenced by the access of the CS to the
altered value of the US, whereas rats with OFC lesions failed to use
such information to guide their responses. This deficit cannot be
attributed to a general inability to inhibit food-related behavior;
when food was presented to OFC rats during devaluation training and
after the devaluation test session, they suppressed consumption of the
pellets. An impairment in the devaluation test would be anticipated if
OFC were essential for establishing or using associations that allow
cues to gain access to representations of reinforcement.
A commonly observed impairment after OFC lesions is an inability to
extinguish or reverse associations that have been established to
reinforcing events (Jones and Mishkin, 1972; Baylis and Gaffan, 1991;
Rolls et al., 1994; Rolls, 1996). For example, although initial
learning often emerges without difficulty, when reinforcement no longer
occurs in extinction, or contingencies are changed in reversal
training, laboratory animals and patients with such damage continue to
respond as though no change had occurred. The current findings are
consistent with those earlier studies, indicating that the behavior of
rats with OFC damage is relatively unaffected by changes in the value
of reinforcement.
It is interesting that human patients with ventromedial prefrontal
damage can often accurately describe task contingencies, but this
knowledge is not sufficient to guide behavior. For example, Rolls et
al. (1994) reports that such patients could verbally describe how task
contingencies had changed during either extinction or reversal
procedures, but nonetheless were not able to alter their behavior
appropriately in a simple visual discrimination task. Similarly, in a
more complex gambling task in which subjects could choose from
different decks of cards to incur rewards and penalties, patients with
ventral prefrontal damage would continue to choose from decks that they
correctly identified as disadvantageous (Bechara et al., 1997). A
related finding in that study was that when patients made those choices
they failed to exhibit anticipatory autonomic responses that were
characteristic of the control subjects. Thus, a lack of
motivational/emotional response appropriate to the expected outcome
might account for the mismatch between knowledge and the patient's
actions. That observation could reflect either an inability to generate
such a response or a lack of access to the appropriate representation
of incentive value that evokes autonomic reactions. As indicated by
recent electrophysiological recordings in OFC, information about the
incentive value of anticipated reinforcers is normally encoded by
neurons in this region in rats (Schoenbaum et al., 1998), providing a
substrate that could be lacking after damage to this system.
An impairment in the ability of cues (or responses) to gain access to
the incentive value of an associated reinforcer would account for
impairment in the devaluation paradigm. If that is the case, then how
does initial learning proceed in animals or humans with prefrontal
damage? Recall that impairments in extinction and reversal learning are
observed, although initial learning is often unimpaired in those tasks.
Similarly, rats in the current study acquired conditioned food cup
responding in the first training phase; they also acquired a normal
conditioned taste aversion. Much evidence indicates that associative
learning can invoke multiple representations of the CS-US relation.
Thus, the associative representation that depends on OFC may occur in
parallel with other associative functions that provide a basis for
initial learning. For example, a CS that is associated with a rewarding
US can itself acquire incentive value. This associative function can be
independently demonstrated by the ability of the CS to serve as the US
in support of new learning, i.e., instrumental learning for secondary
reinforcement. It is interesting that learning based on the acquired
reinforcer properties of a CS, such as second order conditioned
responses, is relatively insensitive to devaluation (Holland and
Rescorla, 1975). Thus, learning that is acquired on such a basis might
be relatively immune to changes in the status of the original US, as
observed in extinction, reversal training, and in the setting of US devaluation.
A critical dependence on OFC for associative information that links
cues to the value of reinforcers or outcomes provides a potential
framework for both the experimental observations in laboratory animals
and the consequences of damage to this region in humans. By this view,
an associative deficit may underlie an inability to effectively use the
motivational guidance provided by an expected outcome, thereby
providing an information processing account for goal neglect. In
serving such a function, it is also evident that OFC is an important
component of circuitry that includes other structures involved in
motivational processes and associative learning. Of particular
importance are direct interconnections between OFC and the basolateral
amygdala complex (Krettek and Price, 1977; Kolb, 1984; Price et al.,
1987; McDonald, 1991). The report providing evidence for OFC neural
encoding of anticipated outcomes (rewarding or aversive) also indicated
that a substantial population of neurons in basolateral amygdala
(ABL) had those same correlates (Schoenbaum et al., 1998).
Approximately 36% of cells in ABL (44 of 121 neurons) had differential
activity in an interval before the delivery of the rewarding or
aversive outcome similar to the correlates that characterized 22% of
cells recorded in OFC (74 of 328 neurons). As might be predicted from
these data, ABL also appears to be important for the normal ability to
gain access to US representations (Hatfield et al., 1996).
Using the same devaluation procedures used in the current study, a
comparable pattern of results was earlier obtained after lesions of the
basolateral amygdala (Hatfield et al., 1996). Similar to the current
findings with OFC-lesioned rats, bilateral neurotoxic lesions of ABL
did not alter acquisition of the initial food cup response and did not
affect taste aversion learning in the second devaluation phase. Lesions
of ABL, like those of OFC, abolished the effect of devaluation on
subsequent responding in the presence of the original CS. Recent
evidence has also shown a lack of US devaluation in guiding the
behavior of monkeys in a visual discrimination task after neurotoxic
amygdala lesions (Malkova et al., 1997). At the same time, lesions of
the amygdala central nucleus (Hatfield et al., 1996) and of medial
temporal lobe structures, either the hippocampus or
entorhinal/perirhinal cortex (Morell, 1997), do not alter the behavior
of rats in this setting; rats with such lesions, like normal rats,
spontaneously decrease CRs in the presence of cues that signal the
devalued US.
These findings implicate connections between OFC and ABL in processes
that depend on stimulus-reinforcer associations. Much other evidence
supports a role for ABL in such learning processes; it is an important
site for convergence of information needed in the acquisition of
associations. Interconnections with OFC may then be critical for
governing the use of that information to guide goal-directed behavior.
Further research is needed to understand interactions between these
subcortical and cortical systems that are important in motivational and
emotional learning processes.
| |
FOOTNOTES |
Received March 16, 1999; revised May 5, 1999; accepted May 6, 1999.
This work was supported by National Institute of Mental Health
Grant RO1 MH53667, Research Scientist Award KO5-MH01149 to M.G.,
and Mentored Clinical Scientist Award K08-AG00882-01 from the National
Institute of Aging to G.S.
Correspondence should be addressed to Dr. Michela Gallagher, Johns
Hopkins University, Department of Psychology, 3400 North Charles
Street, Ames Hall, Baltimore, MD 21218.
| |
REFERENCES |
-
Baylis GC,
Gaffan D
(1991)
Amygdalectomy and ventromedial prefrontal ablation produce similar deficits in food choice and in simple object discrimination learning for an unseen reward.
Exp Brain Res
86:617-622[Web of Science][Medline].
-
Bechara A,
Damasio H,
Tranel D,
Damasio AR
(1997)
Deciding advantageously before knowing the advantageous strategy.
Science
275:1293-1294[Abstract/Free Full Text].
-
Colwill RM
(1993)
An associative analysis of instrumental learning.
Curr Direct Psychol Sci
2:111-116.
-
Critchley HD,
Rolls ET
(1996)
Olfactory neuronal responses in the primate orbitofrontal cortex: analysis in an olfactory discrimination task.
J Neurophysiol
75:1659-1672[Abstract/Free Full Text].
-
Damasio AR
(1994)
In: Descartes error. New York: Putnam.
-
Duncan J,
Emslie H,
Williams P
(1996)
Intelligence and the frontal lobe: the organization of goal-directed behavior.
Cognit Psychol
30:257-303[Web of Science][Medline].
-
Hatfield T,
Han J-S,
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].
-
Holland PC,
Rescorla RA
(1975)
The effect of two ways of devaluing the unconditioned stimulus after first- and second- order conditioning.
J Exp Psychol Anim Behav Proc
1:355-363[Medline].
-
Holland PC,
Straub JJ
(1979)
Differential effects of two ways of devaluing the unconditioned stimulus after Pavlovian appetitive conditioning.
J Exp Psychol
5:65-78.
-
Jones B,
Mishkin M
(1972)
Limbic lesions and the problem of stimulus-reinforcement associations.
Exp Neurol
36:362-377[Web of Science][Medline].
-
Kolb B
(1984)
Functions of the frontal cortex of the rat: a comparative review.
Brain Res Rev
8:65-98.
-
Krettek JE,
Price JL
(1977)
Projections from the amygdaloid complex to the cerebral cortex and thalamus of the rat and cat.
J Comp Neurol
172:687-722[Web of Science][Medline].
-
Krushel LA,
Van Der Kooy D
(1988)
Visceral cortex: integration of the mucosal senses with limbic information in the rat agranular insular cortex.
J Comp Neurol
270:39-54[Web of Science][Medline].
-
Lipton PA,
Alvarez P,
Eichenbaum H
(1999)
Crossmodal associative memory representations in rodent orbitofrontal cortex.
Neuron
22:349-359[Web of Science][Medline].
-
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].
-
McDonald AJ
(1991)
Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the rat.
Neuroscience
44:1-14[Web of Science][Medline].
-
Morell JR
(1997)
The hippocampus: S-R, S-S, and spatial learning.
In: PhD dissertation Duke University.
-
Paxinos G,
Watson C
(1986)
In: The rat brain in stereotaxic coordinates. New York: Academic.
-
Price JL,
Russchen FT,
Amaral DG
(1987)
The limbic region. II. The amygdaloid complex.
In: Integrated systems of the CNS, Pt I. Handbook of chemical neuroanatomy, Vol 5 (Bjorklund A,
Hokfelt T,
Swanson LW,
eds), pp 279-388. Amsterdam: Elsevier.
-
Rolls ET
(1996)
The orbitofrontal cortex.
Philos Trans R Soc Lond B Biol Sci
351:1433-1444[Web of Science][Medline].
-
Rolls ET,
Hornak J,
Wade D,
McGrath J
(1994)
Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage.
J Neurol Neurosurg Psychiatry
57:1518-1524[Abstract/Free Full Text].
-
Rolls ET,
Critchley HD,
Mason R,
Wakeman EA
(1996)
Orbitofrontal cortex neurons: role in olfactory and visual association learning.
J Neurophysiol
75:1970-1981[Abstract/Free Full Text].
-
Saper CB
(1982)
Convergence of autonomic and limbic connections in the insular cortex of the rat.
J Comp Neurol
210:163-173[Web of Science][Medline].
-
Schoenbaum G,
Eichenbaum H
(1995)
Information coding in the rodent prefrontal cortex: I. Single neuron activity in orbitofrontal cortex compared with that in piriform cortex.
J Neurophysiol
74:733-750[Abstract/Free Full Text].
-
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]
-
Schoenbaum G,
Chiba AA,
Gallagher M
(1999)
Neural encoding in orbitofrontal cortex and basolateral amygdala during olfactory discrimination learning.
J Neurosci
19:1876-1884[Abstract/Free Full Text].
-
Swanson LW
(1992)
In: Brain maps: structure of the rat brain. New York: Elsevier.
-
Thorpe SJ,
Rolls ET,
Maddison S
(1983)
The orbitofrontal cortex: neuronal activity in the behaving monkey.
Exp Brain Res
49:93-115[Web of Science][Medline].
Copyright © 1999 Society for Neuroscience 0270-6474/99/19156610-05$05.00/0
This article has been cited by other articles:
|
|
|
|
 
C. Padoa-Schioppa
Range-Adapting Representation of Economic Value in the Orbitofrontal Cortex
J. Neurosci.,
November 4, 2009;
29(44):
14004 - 14014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Roesch, T. Singh, P. L. Brown, S. E. Mullins, and G. Schoenbaum
Ventral Striatal Neurons Encode the Value of the Chosen Action in Rats Deciding between Differently Delayed or Sized Rewards
J. Neurosci.,
October 21, 2009;
29(42):
13365 - 13376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. S. Chib, A. Rangel, S. Shimojo, and J. P. O'Doherty
Evidence for a Common Representation of Decision Values for Dissimilar Goods in Human Ventromedial Prefrontal Cortex
J. Neurosci.,
September 30, 2009;
29(39):
12315 - 12320.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. McDannald and G. Schoenbaum
Toward a Model of Impaired Reality Testing in Rats
Schizophr Bull,
July 1, 2009;
35(4):
664 - 667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.S. Man, H.F. Clarke, and A.C. Roberts
The Role of the Orbitofrontal Cortex and Medial Striatum in the Regulation of Prepotent Responses to Food Rewards
Cereb Cortex,
April 1, 2009;
19(4):
899 - 906.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.C. Walker, T.W. Robbins, and A.C. Roberts
Differential Contributions of Dopamine and Serotonin to Orbitofrontal Cortex Function in the Marmoset
Cereb Cortex,
April 1, 2009;
19(4):
889 - 898.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. van Duuren, J. Lankelma, and C. M. A. Pennartz
Population Coding of Reward Magnitude in the Orbitofrontal Cortex of the Rat
J. Neurosci.,
August 20, 2008;
28(34):
8590 - 8603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. C. HOLLAND
Cognitive versus stimulus-response theories of learning
Learn Behav,
August 1, 2008;
36(3):
227 - 241.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Furuyashiki, P. C. Holland, and M. Gallagher
Rat Orbitofrontal Cortex Separately Encodes Response and Outcome Information during Performance of Goal-Directed Behavior
J. Neurosci.,
May 7, 2008;
28(19):
5127 - 5138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C. Kerfoot, I. Agarwal, H. J. Lee, and P. C. Holland
Control of appetitive and aversive taste-reactivity responses by an auditory conditioned stimulus in a devaluation task: A FOS and behavioral analysis
Learn. Mem.,
August 29, 2007;
14(9):
581 - 589.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Murray, J. P. O'Doherty, and G. Schoenbaum
What We Know and Do Not Know about the Functions of the Orbitofrontal Cortex after 20 Years of Cross-Species Studies
J. Neurosci.,
August 1, 2007;
27(31):
8166 - 8169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gil, R. J. De Marco, and R. Menzel
Learning reward expectations in honeybees
Learn. Mem.,
July 12, 2007;
14(7):
491 - 496.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. van Duuren, F. A. N. Escamez, R. N.J.M.A. Joosten, R. Visser, A. B. Mulder, and C. M.A. Pennartz
Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task
Learn. Mem.,
June 11, 2007;
14(6):
446 - 456.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R.J Dolan
The human amygdala and orbital prefrontal cortex in behavioural regulation
Phil Trans R Soc B,
May 29, 2007;
362(1481):
787 - 799.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. Ostlund and B. W. Balleine
Orbitofrontal Cortex Mediates Outcome Encoding in Pavlovian But Not Instrumental Conditioning
J. Neurosci.,
May 2, 2007;
27(18):
4819 - 4825.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y Chudasama, J. Kralik, and E. Murray
Rhesus Monkeys with Orbital Prefrontal Cortex Lesions Can Learn to Inhibit Prepotent Responses in the Reversed Reward Contingency Task
Cereb Cortex,
May 1, 2007;
17(5):
1154 - 1159.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Pecina, K. S. Smith, and K. C. Berridge
Hedonic Hot Spots in the Brain
Neuroscientist,
December 1, 2006;
12(6):
500 - 511.
[Abstract]
[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]
|
|
|
|
|
|
|
S. B. Ostlund and B. W. Balleine
Lesions of Medial Prefrontal Cortex Disrupt the Acquisition But Not the Expression of Goal-Directed Learning
J. Neurosci.,
August 24, 2005;
25(34):
7763 - 7770.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schoenbaum and B. Setlow
Cocaine Makes Actions Insensitive to Outcomes but not Extinction: Implications for Altered Orbitofrontal-Amygdalar Function
Cereb Cortex,
August 1, 2005;
15(8):
1162 - 1169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. McDannald, M. P. Saddoris, M. Gallagher, and P. C. Holland
Lesions of Orbitofrontal Cortex Impair Rats' Differential Outcome Expectancy Learning But Not Conditioned Stimulus-Potentiated Feeding
J. Neurosci.,
May 4, 2005;
25(18):
4626 - 4632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Roullet, F. Lienard, F. Datiche, and M. Cattarelli
Fos protein expression in olfactory-related brain areas after learning and after reactivation of a slowly acquired olfactory discrimination task in the rat
Learn. Mem.,
May 1, 2005;
12(3):
307 - 317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. L. Cox, A. Andrade, and I. S. Johnsrude
Learning to Like: A Role for Human Orbitofrontal Cortex in Conditioned Reward
J. Neurosci.,
March 9, 2005;
25(10):
2733 - 2740.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. W. Johnson, D. M. Bannerman, N. P. Rawlins, R. Sprengel, and M. A. Good
Impaired Outcome-Specific Devaluation of Instrumental Responding in Mice with a Targeted Deletion of the AMPA Receptor Glutamate Receptor 1 Subunit
J. Neurosci.,
March 2, 2005;
25(9):
2359 - 2365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. S. Crombag, G. Gorny, Y. Li, B. Kolb, and T. E. Robinson
Opposite Effects of Amphetamine Self-administration Experience on Dendritic Spines in the Medial and Orbital Prefrontal Cortex
Cereb Cortex,
March 1, 2005;
15(3):
341 - 348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Fuchs, K. A. Evans, M. P. Parker, and R. E. See
Differential Involvement of Orbitofrontal Cortex Subregions in Conditioned Cue-Induced and Cocaine-Primed Reinstatement of Cocaine Seeking in Rats
J. Neurosci.,
July 21, 2004;
24(29):
6600 - 6610.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schoenbaum
Affect, Action, and Ambiguity and the Amygdala-Orbitofrontal Circuit. Focus on "Combined Unilateral Lesions of the Amygdala and Orbital Prefrontal Cortex Impair Affective Processing in Rhesus Monkeys"
J Neurophysiol,
May 1, 2004;
91(5):
1938 - 1939.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Izquierdo and E. A. Murray
Combined Unilateral Lesions of the Amygdala and Orbital Prefrontal Cortex Impair Affective Processing in Rhesus Monkeys
J Neurophysiol,
May 1, 2004;
91(5):
2023 - 2039.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Datta, V. Mavanji, J. Ulloor, and E. H. Patterson
Activation of Phasic Pontine-Wave Generator Prevents Rapid Eye Movement Sleep Deprivation-Induced Learning Impairment in the Rat: A Mechanism for Sleep-Dependent Plasticity
J. Neurosci.,
February 11, 2004;
24(6):
1416 - 1427.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. K. Goerendt, A. D. Lawrence, and D. J. Brooks
Reward Processing in Health and Parkinson's Disease: Neural Organization and Reorganization
Cereb Cortex,
January 1, 2004;
14(1):
73 - 80.
[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]
|
|
|
|
|
|
|
A. Pears, J. A. Parkinson, L. Hopewell, B. J. Everitt, and A. C. Roberts
Lesions of the Orbitofrontal but not Medial Prefrontal Cortex Disrupt Conditioned Reinforcement in Primates
J. Neurosci.,
December 3, 2003;
23(35):
11189 - 11201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schoenbaum and B. Setlow
Lesions of Nucleus Accumbens Disrupt Learning about Aversive Outcomes
J. Neurosci.,
October 29, 2003;
23(30):
9833 - 9841.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Gottfried, J. O'Doherty, and R. J. Dolan
Encoding Predictive Reward Value in Human Amygdala and Orbitofrontal Cortex
Science,
August 22, 2003;
301(5636):
1104 - 1107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Blundell, G. Hall, and S. Killcross
Preserved Sensitivity to Outcome Value after Lesions of the Basolateral Amygdala
J. Neurosci.,
August 20, 2003;
23(20):
7702 - 7709.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. C. Cromwell and W. Schultz
Effects of Expectations for Different Reward Magnitudes on Neuronal Activity in Primate Striatum
J Neurophysiol,
May 1, 2003;
89(5):
2823 - 2838.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Bohn, C. Giertler, and W. Hauber
Orbital Prefrontal Cortex and Guidance of Instrumental Behavior of Rats by Visuospatial Stimuli Predicting Reward Magnitude
Learn. Mem.,
May 1, 2003;
10(3):
177 - 186.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Killcross and E. Coutureau
Coordination of Actions and Habits in the Medial Prefrontal Cortex of Rats
Cereb Cortex,
April 1, 2003;
13(4):
400 - 408.
[Abstract]
[Full Text]
[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]
|
|
|
|
|
|
|
A. N. Mead and D. N. Stephens
Selective Disruption of Stimulus-Reward Learning in Glutamate Receptor gria1 Knock-Out Mice
J. Neurosci.,
February 1, 2003;
23(3):
1041 - 1048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. W. Balleine, A. S. Killcross, and A. Dickinson
The Effect of Lesions of the Basolateral Amygdala on Instrumental Conditioning
J. Neurosci.,
January 15, 2003;
23(2):
666 - 675.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. Small, R. J. Zatorre, A. Dagher, A. C. Evans, and M. Jones-Gotman
Changes in brain activity related to eating chocolate: From pleasure to aversion
Brain,
September 1, 2001;
124(9):
1720 - 1733.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
S. Datta
Avoidance Task Training Potentiates Phasic Pontine-Wave Density in the Rat: A Mechanism for Sleep-Dependent Plasticity
J. Neurosci.,
November 15, 2000;
20(22):
8607 - 8613.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Hauber, I. Bohn, and C. Giertler
NMDA, But Not Dopamine D2, Receptors in the Rat Nucleus Accumbens Are Involved in Guidance of Instrumental Behavior by Stimuli Predicting Reward Magnitude
J. Neurosci.,
August 15, 2000;
20(16):
6282 - 6288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schoenbaum, A. A. Chiba, and M. Gallagher
Changes in Functional Connectivity in Orbitofrontal Cortex and Basolateral Amygdala during Learning and Reversal Training
J. Neurosci.,
July 1, 2000;
20(13):
5179 - 5189.
[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]
|
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
