This study tested whether monkeys with lesions to Area 12 of the orbitofrontal cortex, which has been linked to safety signal learning and flexible decision making, would show impairments in object discrimination reversal learning. Four monkeys received lesions to Area 12 while four control monkeys received sham operations. On an object discrimination reversal task, monkeys with Area 12 lesions learned the initial discrimination as quickly as controls but made fewer reversal errors, though this difference was not significant. The study suggests that additional control monkeys may be needed to fully assess the effects of Area 12 lesions on reversal learning abilities.

1. RESULTS
This investigation was supported, in part, by the National Institute of Health and Howard Hughes Medical Institute
METHODS
Subjects - Area 12: Four monkeys received ibotenic acid
injections in Area 12 under anesthesia.
Controls: Four monkeys received sham-operations
(opening of the skull but no injections).
Object Discrimination Reversal (ODR) is a paradigm
measuring goal –directed flexible decision making in a
Wisconsin General Testing Apparatus (WGTA). It uses
two objects as stimuli.
INTRODUCTION
• Area 12 of the orbitofrontal
cortex (OFC) is known to
play a critical role in
behavioral flexibility.
• Studies in our lab have
shown that lesions of Area
12 in monkeys impaired
safety signal learning, i.e. the
ability to inhibit fearful
responses in presence of
safety cues (A. Kazama,
unpublished data).
• Earlier studies have also
reported that Area 12
damage impairs object
discrimination reversal
learning, i.e. the ability to
inhibit responses to
rewarded objects when they
are not rewarded anymore
(flexible goal-directed
responses; Roberts, 2006;
Wallis, 2007).
• In the present study, we
tested whether monkeys with
area 12 lesions that showed
safety signal learning
impairment will also
demonstrate object
discrimination reversal
deficits.
CONCLUSION
• Acquisition of the reward
contingencies was not
impaired by damage to Area
12.
• Also, damage to Area 12
spared reversal learning
abilities.
• This lack of impairment could
be due to the large variation in
errors made by control
animals.
• When comparing monkeys
with Area 12 with another set
of 6 control monkeys tested in
the same way (Kazama &
Bachevalier, 2008), animals
with Area 12 lesions made
more errors than controls [p =
0.07 with a large effect size :
r=0.5595].
• Thus, additional control
animals should be added to
our study to confirm whether
or not damage to Area 12
impacts flexible decision
making.
• Further studies should also
test the same animals in
additional tasks of decision-
making to confirm the results
on the ODR task.
Fig. 1 : Extent of Area 12 orbitofrontal damage was verified
via neuroimaging procedures (FLAIR). View of the intended
lesion Area is taken from the ventral view. The lesion was
restricted to the orbital frontal cortex, with the white matter
beneath the cortical mantle being spared in all cases.
STIMULUS-REWARD ASSOCIATIVE LEARNING: Object Discrimination
Reversal in Rhesus Macaques with Lesions in Area 12
Joshua Davila, Andy Kazama, Jocelyne Bachevalier
Department of Psychology, Division of Developmental Cognitive Neuroscience, Yerkes National Primate Research Center, Atlanta, GA 30322; Center for
Behavioral Neuroscience, Emory University, Atlanta, GA 30322
CITATIONS
Izquierdo, A & Murray, EA (2004). Combined unilateral lesions of the amygdala and orbital
prefrontal cortex impair affective processing in rhesus monkeys. Journal of
Neurophysiology, 91, 2023-2039.
Izquierdo, A, Suda, RK & Murray, EA (2004). Bilateral prefrontal cortex lesions in rhesus
monkeys disrupt choices guided by both reward value and reward contingency. The
Journal of Neuroscience, 24, 7540-7548.
Kazama AM, Bachevalier J (2008). Selective aspiration or neurotoxic lesions of orbital
frontal area
s 11 and 13 spared monkeys’ performance on the object discrimination
reversal task. J Neurosci,. 29(9):2794 –2804
Roberts AC (2006) Primate orbitalfrontal cortex and adaptive behaviour. TICS 10:83-90.
Wallis JD (2007) Orbitofrontal cortex and its contribution to decision-making. Annu Rev
Neurosci 30:31-56.
ACKNOWLEDGEMENTS
This research was supported by the National Institute for Mental Health
(MH086947) and the National Center for Research Resources (P51RR165)
currently supported by the Office of Research Infrastructure Programs OD
P51OD11132.
Research reported in this poster was supported Emory Initiative for Maximizing
Student Development of the National Institutes of Health under award
R25GM099644. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the National Institutes of Health.
This material is based upon work supported by the Howard Hughes Medical
Institute Science Education Program award #52006923 to Emory University.
Any opinions, findings, and conclusions or recommendations expressed in this
material are those of the author(s) and do not necessarily reflect the views of
the Howard Hughes Medical Institute or Emory University.
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ACQ RVR 1 RVR 2 RVR 3 RVR 4 RVR 5 RVR 6
AverageGroupErrors
1-Pair ODR
Reversal Errors
Control
Area 12
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TotalAverageGroupErrors
1-Pair ODR
Total Average Reversal Errors
Control
Area 12
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TotalAveragePerseveration
1-Pair ODR
Total Average Perseveration
Monkeys with Area 12 lesions learned the discrimination as rapidly as controls
[p=0.307]; although they made less reversal errors than controls. This group
difference did not reach significance, [F(1,6)=0.787, p=0.409, r=0.299].
Monkeys with Area 12 lesions made less perseverative
errors than controls, but this group did not reach
significance [F(1,6)=0.176, p=0.689, r=0.147].
Trial 1
+ +
Trial 2
+ -
Criterion reached, 28/30 trials
followed by 24/30 trials
Reversal 1
- +
Criterion reached, 28/30 trials
followed by 24/30 trials and
repeated for six reversals total
Error Trial
+ -
Perseveration
+ -
O
Trial repeated until rewarded object
chosen