Rev. Neurosci.

2015; 26(1): 1–11

Frank A. Jonker*, Cees Jonker, Philip Scheltens and Erik J.A. Scherder

The role of the orbitofrontal cortex in cognition

and behavior
Abstract: The orbitofrontal cortex (OFC) plays a crucial Introduction
role in behavior and is a common site for damage due to
different types of injuries, e.g., closed head injuries, cer-
The orbitofrontal cortex (OFC) is a key structure for appro-
ebrovascular accidents, tumors, neurosurgical interven-
priate social behavior (Bechara et al., 1994; Rolls, 2000).
tions. Despite the (severe) behavioral changes following
Behavioral changes caused by OFC damage generally
OFC lesions, persons with damage to the OFC appear to be
have been categorized into forced collectionism (hoard-
cognitively intact, i.e., at least when assessed by means of
ing) (Cohen et al., 1999; Hahm et al., 2001; Volle et al.,
standard neuropsychological tests. Meanwhile, neuropsy-
2002), disinhibited behavior (Namiki et al., 2008; Poletti,
chological tests addressing reversal learning, gambling,
Lucetti and Bonuccelli, 2010), pathologic gambling (Floris
and social cognition show a decline in these patients.
et al., 2008), obsessive compulsive behavior (Ogai et al.,
The goal of the present review is to link the performance
2005), behavioral characteristics of autism, psychopa-
of these latter neuropsychological tests to behavior. The
thy (Blair and Cipolotti, 2000; Umeda et al., 2010), and
results suggest that in patients with orbitofrontal lesions,
impulsiveness (Berlin et al., 2004). The common factor in
reversal learning is more associated with behavioral disin-
behavioral changes in the different studies is the inability
hibition and that impairment in recognition of expressed
to control or correct behavior on given feedback.
emotion is more associated with social inappropriate
In the last decade, neuropsychological research
behavior. The faux pas test (theory of mind) appears not to
(Hanna-Pladdy, 2007) focused on the question, ‘To what
be sensitive to orbitofrontal lesions. Future studies should
extent are changes in behavior, following lesions in the
involve a larger numbers of patients with well-defined
OFC, related to cognitive dysfunctions?’ The general view
locations in the OFC and should integrate specific neu-
in clinical neuropsychology is that changes in behav-
ropsychological tests and quantitative behavioral meas-
ior, especially following frontal lobe lesion, are strongly
ures to better understand the contribution of the OFC to
related to deficits in executive functions. However, despite
cognition and behavior.
the above-described changes in behavior, most patients
appear to be cognitively intact, at least when assessed by
Keywords: behavior disorders; gambling task; orbitofron-
means of standard neuropsychological tasks appealing to
tal cortex damage; reversal learning; theory of mind (ToM).
executive functions (Blair and Cipolotti, 2000; Fujii et al.,
2005; Reid-Arndt et al., 2007; Namiki et al., 2008).
DOI 10.1515/revneuro-2014-0043 In their elaborate review, Zald and Andreotti (2010)
Received June 27, 2014; accepted August 24, 2014; previously suggest that there are at least three cognitive functions that
published online September 25, 2014
seem to be related to OFC damage; they also recommend
tests that assess specific cognitive function. (1) Learning
*Corresponding author: Frank A. Jonker, GGZ Altrecht, Vesalius and adapting to changing reinforcement contingencies.
Centre for Neuropsychiatry Woerden, Department of Clinical The test they recommend is the reversal learning task (Rolls
Neuropsychology, VU University Amsterdam, Polanerbaan 2,
et al., 1994), which measures the ability to utilize cues in
NL-3447 GN Woerden, The Netherlands,
the environment to predict future rewarding or aversive
e-mail: fr.jonker@altrecht.nl, f.a.jonker@vu.nl
Cees Jonker: Department EMGO Institute for Health and Care events (Berlin et al., 2004). (2) Decision-making tasks.
Research, VU University Medical Center, Van der Boechorststraat 7, They recommend the Iowa gambling task (IGT), which
1081 BT, Amsterdam, The Netherlands measures the ability to regulate behavioral responses in
Philip Scheltens: Alzheimer Centre and dept neurology, VU the context of changing reinforcement contingencies,
University Medical Center, Postbus 7057, 1007 MB, Amsterdam,
based on rewards and punishment (Bechara et al., 1994).
The Netherlands
Erik J.A. Scherder: Department Clinical Neuropsychology, VU (3) Social processing and theory of mind (ToM). In ToM, the
University Amsterdam, Van der Boechorststraat 1, 1081 BT, ability to attribute mental states and intentions to oneself
Amsterdam, The Netherlands and others and the recognition of expressed emotion are

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
2 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior

the two core components of social processing and essen-

the reversal learning task

No relationship between

No relationship between

and aggressive behavior

reversal learning scores

Relationship cognition-

and antisocial behavior

A relationship between

A relationship between

A relationship between
reversal learning score
tial for human non-verbal communication (Frith and Frith,

reversal learning and

2003). The most used test for ToM is the faux pas test

and disinhibition
reversal test and
(Stone et al., 1998); it requires the capacity to judge inap-

disinhibition

disinhibition
propriate behavior in social situations. Recognizing a faux

behavior
pas requires empathic understanding, elements of mental-
izing, and an understanding that there might be a differ-
ence between the appreciation of the emotional impact of
a statement of the character who commits the faux pas and

disinhibition, impulsiveness, social

questionnaire: disinhibition, social
inappropriateness, perseveration,
that of the listener (Baron-Cohen et al., 1999). The test for

Frontal behavior questionnaire:

Antisocial personality disorder

Self-report impulsivity, frontal

Aggressive narcissism (PCL-R)
recognition of expressed emotion assesses an individual’s
ability to recognize social emotions based on pictures of

behavior questionnaire
faces with emotional expressions. Both the faux pas test

Behavioral measures

and cooperativeness
The frontal behavior

inappropriateness
and recognition of expressed emotions test measure two
different aspects of social processing.
Up to now, it is unclear to what extent these recom-

(DSM-IV)
mended cognitive functions are related to behavioral changes
following orbitofrontal lesions. The goal of this review is
to address studies that investigated the performance of the
neuropsychological tests as suggested by Zald, in relation to

Which dysfunctional cognitive systems

stimulus reinforcement test and social

What are the cognitive and emotional
underpin his profound emotional and
changes in daily behavior following OFC damage.

What is the relationship between a

differences between acquired and

Is borderline personality disorder

performance on a reversal task?

social behavioral impairment?

(impulsivity), related with OFC

developmental psychopathy?

Is impulsiveness related to

and behavioral problems?

Methods
Research question

The search focused on PubMed and PsycINFO from 1980 through

2013, combining the keywords ‘orbitofrontal cortex’, ‘ventromedial

dysfunction?
prefrontal cortex’ with the terms ‘brain injury’, ‘lesions’, ‘cognitive
dysfunctions’, ‘executive functions’ and ‘reversal learning’, ‘IOWA
gambling task’, ‘social cognition’, ‘behavioral changes’. Studies were
included if they contained clinical and laboratory cognitive test data
related to OFC damage, to behavioral changes in daily life, and to
Impairment on reversal

Impairment on reversal

Impairment on reversal
cognitive functions. Studies describing neurodegenerative diseases
reversal learning test

reversal learning test

Neuropsychological

(e.g., frontotemporal dementia, Parkinson disease, Huntington dis-

No impairment on

No impairment on

ease) were excluded. We use the term ‘orbitofrontal cortex’ to refer

learning test
to the combination of the medial and ventral parts of the oribito-
frontal cortex, given the fact that these regions are highly intercon-
nected and anatomically difficult to distinguish (Fellows, 2007).
task

test

test

Fifteen studies with well-defined lesions in the OFC were found in

which both the traditional task and one or more tasks as suggested
by Zald are described in relation with behavioral outcome measures.
1 patient with damage to

12 patients with ventral

To describe the changes in behavior, the clinical descriptions and/or

1 patient with bilateral

damage, bilateral and

damage, bilateral and

23 patients with OFC

23 patients with OFC

diagnostic categories used in the different studies will be presented.

the right OFC region

Some studies using more than one test sensitive to the OFC will occur
more than once in the following subsections.
frontal lesion
OFC damage
Table 1 The reversal learning task.

OFC lesions

unilateral

unilateral

Results
Berlin et al., 2005

Berlin et al., 2004

Rolls et al., 1994

Reversal learning task (Table 1)

Cipolotti, 2000

Mitchell et al.,
Blair and
Author

Three of the five studies (Rolls et al., 1994; Berlin et al.,

2006a

2004, 2005) found a positive relationship between deficits

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior 3

on the reversal learning task and increase of impulsivity. made several perseverative errors, due to a low frustration
In one study comparing patients with ventromedial pre- tolerance, and the test could not be fully completed. No
frontal cortex (VMPFC) (n = 12) damage with non-VMPFC- deficits were found on two reversal learning tasks (i.e., the
damaged patients (n = 7), a severe impairment on the Four-Pack and the One-Pack Card-Playing tasks), which
reversal learning test was found in the VMPFC-damaged both measure to reverse a learned response (Blair and
group (Rolls et al., 1994). The location of lesions, mostly Cipolotti, 2000).
head injury or stroke, was determined with MRI and CT There were also no reversal learning deficits found in
scans. Of interest is that these deficits occurred in combi- a case study of a 51-year-old patient who suffered a pen-
nation with normal scores on a number of standard neu- etrating head injury at the age of 14 years in a cycling acci-
ropychological tests {i.e., paired associate learning, verbal dent (Mitchell et al., 2006a). A CT scan showed bilateral
IQ [from the Wechsler Adult Intelligence Scale – Revised orbitofrontal lesions. The patient served at least 15 years in
(WAIS-R)], Tower of London task}, tests that appeal to prison and showed aggressive, sexual offensive behavior.
planning and memory for planned actions (Rolls et al., He met the criteria of a psychopathy on the Psychopathy
1994). A staff questionnaire was administered to capture Check List – Revised (PCL-R). To address the behavioral
behavioral characteristics, e.g., disinhibition or social aspects, they found that the patient had a severe elevated
inappropriateness, violence, verbal abusiveness, uncoop- score on the unemotional characteristics, indicating
erativeness, on a five-point Likert scale. The performance antisocial behavior and lifestyle (Mitchell et al., 2006a).
on the behavioral questionnaire and the reversal tests The patient had an above average IQ and scored within
was highly correlated, especially for disinhibited behav- the normal range on standard neuropsychological tests,
ior (Spearman’s ρ = 0.76, p = 0.002) (Rolls et al., 1994). The including executive (WCST). Despite showing no rever-
authors conclude that behavioral disinhibition might be sal learning deficits, he was unable to reverse behavio-
due to reward and punishment insensitivity . ral responses in daily life, and the authors conclude that
In practically identical studies (Berlin et al., 2004, the patient’s aggressive behavior is the consequence of
2005), the aim was to study impulsiveness in patients (n = 23) an impaired ‘social response reversal system’, a multi-
with OFC damage (bilaterally or unilaterally) in relation to neurocognitive system that is involved in the processing
performance on a reversal learning task. On an informant of cognitive and social signals (Blair and Cipolotti, 2000;
behavioral questionnaire (Rolls et al., 1994), there was a Mitchell et al., 2006a).
significantly higher total score, indicating more behavio- In summary, the reversal learning task was found
ral problems, for the OFC group compared with non-OFC to be related to behavioral disinhibition in three studies
patients and controls (p < 0.005). Interestingly, increased and not with antisocial behavior. Of note, these deficits
self-report impulsivity of patients with OFC lesions was occurred independently of the performance on a number
correlated to reward and punishment deficits reflected by of standard neuropsychological tests, including executive
the reversal task; daily behavioral impulsivity and reversal functions.
learning performance were negatively correlated (r = -0.42,
p < 0.01). Interestingly, patients with OFC lesion had a sig-
nificantly faster sense of time, subjectively overestimating The IOWA gambling task (Table 2)
time, compared with healthy controls (p = 0.002).
No reversal learning deficits were found in a case Three of four studies (Mitchell et al., 2006a; Funayama
study describing a 56-year-old patient with bilateral et al., 2010; Poletti et al., 2010) describe a relationship
frontal lobe damage, involving the OFC, left temporal between the negative score on the IGT and behavio-
lobe, the left amygdala, following trauma. On a behav- ral changes. In one case study (Funayama et al., 2010),
ioral level, the patient met the Diagnostic and Statisti- a patient with a bilateral orbitofrontal damage scored
cal Manual of Mental Disorders, Fourth Edition (DSM-IV, extreme low on the IGT. The behavior was classified as a
1994) criteria of an antisocial personality disorder. His ‘squalor syndrome’, a disorder characterized by extreme
behavior existed of aggression, reckless regarding safety domestic and self-neglect (Funayama et al., 2010). More-
of others, reduced ‘empathy’, and disrupted social inter- over, the patient compulsively collected unnecessary
actions. He met the criteria for antisocial personality items; she acknowledged that she had a problem but was
disorder (DSM-IV, 1994). His cognitive profile was incon- unable to alter her behavior correspondingly. The authors
clusive, he had a normal IQ, and his scores on some tradi- conclude that this type of behavior is not due to neuro-
tional executive tests (STROOP, Trailmaking) were normal. cognitive disorders, as the patient showed no deficits on
However, on the Wisconsin Card Sorting Test (WCST), he standard neuropsychological tests. Hoarding is seen as

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
 4 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior

a separate disorder from obsessive compulsive disorder,

Relationship cognition-behavior

behavior and obsessive impulse

Impaired IGT might contribute

given the fact that she did not show fear of losing things

scores on the IGT and squalor

No relation between IGT and

to the inflexibility to adapt

or displayed any compulsions or stereotypic behavior

A relationship between
(Funayama et al., 2010). The orbitofrontal lesion is con-

Relationship IGT and

sistent with the behavioral characteristics of hoarding,
and the extreme low score on the IGT showed that the
disinhibition

disinhibition
patient had deficits in decision-making and was insensi-

shopping

behavior
tive of future consequences .
The second study (Mitchell et al., 2006a) compared
a bilateral orbitofrontal damaged patient, an ‘acquired
sociopath’ (Damasio, 1994), with developmental psycho-
collecting behavior, shopping for
Squalor syndrome: extreme self-

Out-of-control sexual behavior

neglect and domestic squalor;

Aggressive narcissism (PCL-R)

paths, forensic controls (non-psychopathic control resi-

dents), and a community control group. The patient met
the threshold on the PCL-R for psychopathy, especially
Behavioral measures

Disinhibition (FrSBe)

unnecessary thing

on the affective and interpersonal subscales. The find-

ings show that the orbitofrontally damaged patient had a
significant impaired score on the IGT compared with the
other groups. Notably, the developmental psychopaths
also made more errors than the forensic controls. The
authors (Mitchell et al., 2006a) conclude that the impaired
Describe the neuropsychological

Describe the neuropsychological

decision-making capacity (IGT) might have been contrib-

emotional differences between
mechanisms that explain his

acquired and developmental

uted to the inflexibility to adapt behavior, with the remark

squalor syndrome after OFC

What are the cognitive and

pathologic hypersexuality
changes in a patient with

changes in a patient with

that the gambling task might also be an index for reversal

Explore the cognitive

learning. Of note, the patient showed an above average

behavioral problems
Research question

score on standard neuropsychological tests, including

psychopathy?

executive functioning.
A 75-year-old patient is presented in a case study with
damage

a right orbitofrontal lesion who had undergone behav-

ioral changes during the last years; he became more
sexual active and he felt the urge to sexually approach
Neuropsychological task

young women. Of interest, the lesion occurred 42 years

No impairment on IGT

ago. Despite the small positive score on the IGT (Poletti

Impairment on IGT

Impairment on IGT

Impairment on IGT

et al., 2010), indicating decision-making capacity, he

was unable to adapt an effective strategy on the IGT. The
clinical characteristics met the criteria for DSM-IV-TR
diagnosis ‘impulse control disorder’. On standard neu-
ropsychological tests, he showed an preserved cogni-
tive functioning (memory, language, attention, abstract
Patient with right OFC

reasoning, visuospatial skills, constructional praxis),

Patient with bilateral

Patient with bilateral

Patient with bilateral

OFC damage patient

including executive test. Of interest is that he showed

pathologic score on the Cognitive Estimation Task (Poletti
OFC damage
OFC lesion

OFC lesion

et al., 2010). The authors conclude that right OFC is associ-

Table 2 The IOWA gambling task.

ated with impulse control, given the fact that the patient
was not able to change his strategy on negative feedback
reflected by the small score on IGT, and he was unable to
Funayama et al., 2010

adapt toward less risky behavior.

Mitchell et al., 2006a
Namiki et al., 2008

Poletti et al., 2010

A normal score on the IGT was found in a 54-year-old

male patient with remarkable personality changes and
with marked disinhibited behavior (e.g., random pur-
Author

chases) and social problems (e.g., aggressive, indifferent)

after a traumatic bilateral orbitofrontal lesion (Namiki

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior 5

et al., 2008). The patient showed no impairments on the

Relationship cognition-behavior

A relationship between a group

Deficient performance on facial

No relationship between facial

social cognitive measures and
WAIS-R (IQ 115), the WCST, and the Behavioral Assess-

No clear relationship between

expression and inappropriate

recognition and disinhibition

social behavior recognition
of cognitive measures and
ment of Dysexecutive Syndrome (BADS). On the Frontal

contributes to reactive
Systems Behaviour Scale (FrSBe) (Grace et al., 1999), a

antisocial behavior
46-item behavior rating scale designed to provide a total
frontal disturbance score on three subscale scores apathy,
disinhibition, and executive function, there was a signifi-

aggression

behavior
cant difference in the observer rating (117) vs. patients (59)
score on disinhibition. Higher scores (T-score > 65) indi-
cated impaired behavior. The authors conclude that the

Behavioral measures
behavioral changes in the absence of impaired scores on

Disinhibition (FrSBe)
personality disorder

narcissism (PCL-R)

Characteristics of
neuropsychological tests, including standard executive

(DSM-IV criteria)
functions tests and IGT, are due the complex framework

autism (AQ)
Aggressive
Antisocial
of decision making of the frontal lobe and the small lesion
in the OFC.
In summary, three studies found a relationship
between a negative score on the IGT, indicating an impair-

that explain his behavioral problem

like) and behavioral disturbances?
ment in decision making, and behavioral characteristics

What cognitive functions underpin

Explore the cognitive mechanisms

the personality changes (autistic-
emotional and social behavioral
systems underpin his profound

emotional differences between

of impulse control problems. Overall, an above average

Which dysfunctional cognitive

acquired and developmental

score on standard neuropsychological tests, including

What are the cognitive and

executive functioning, was found in all studies. Research question

psychopathy?
Social processing and ToM (Table 3)
impairment?

Two studies (Blair and Cipolotti, 2000; Mitchell et al.,

2006a) of four found a significant impairment on the facial
recognition expression of happiness and anger in relation
impairments; social cognition impaired

expression recognition (exceptions are

disgust, sadness, happiness). ToM, no

in emotional attribution of fear, anger,

expressions of sadness and surprise),

no social cognition impairments (ToM

BFRT; lower score on happiness and

with antisocial-aggressive behavior. The patient in the

Mild impairment on faux pas test

first study, already described in both Reversal Learning
expression recognition (anger,
Severe problems with emotion

Severe problems with emotion

Task and the IOWA Gambling Task sections, showed a

and embarrassment others
Neuropsychological task

significant impairment in the facial recognition expres-

sion of happiness and anger (Mitchell et al., 2006a). No
deficits were found in attributing mental states of others
(ToM), including faux pas and reading the mind in the
cartoons)

eyes task. The patient has an above average IQ and scored

anger

within the normal range on standard neuropsychological

tests, including executive (WCST). He did significantly fail
on the ‘social situations task’, a task that evokes an emo-
Patient with right OFC

Patient with bilateral

Patient with bilateral

tional reaction on social misbehaviors. The task is said

right VMPFC damage
medial PFC, left and
Two patients with

to be sensitive to adapting one’s behavior to disapprov-

ing social cues (Blair and Cipolotti, 2000). The authors
Table 3 Social processing and ToM.

OFC damage

OFC damage

BFRT, Benton facial recognition test.

OFC lesions

concluded that aggressive behavior is a consequence of a

region

dysfunctional ‘social response reversal system’, a system

that is insensitive to disapproving social cues (Blair and
Cipolotti, 2000).
Umeda et al., 2010

Namiki et al., 2008

Blair and Cipolotti,

In the other case study (see section Reversal learn-

ing) involving OFC in a 56-year-old patient with bilateral
Mitchell et al.,

frontal lobe damage, Blair and Cipolotti (2000) also found

Author

significant impairment on the facial recognition expres-

2006a
2000

sion of happiness and anger. These deficits could not be

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
6 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior

attributed to a general face processing impairment or to disinhibited behavior (e.g., random purchases) (see the
auditory deficits. No deficits were found in attributing IOWA Gambling Task section) (Namiki et al., 2008). The
mental states of others (ToM), including the faux pas. Of patient scores significantly low on the facial expression
interest is that the patient failed to attribute fear, anger, recognition task, especially on emotions recognizing hap-
and embarrassment to others on an emotional attribu- piness (p < 0.001), sadness (p < 0.001), and anger (p < 0.001).
tion test, a test where the patient had to appraise the Despite the normal score on the IGT, the patient made dis-
emotional state of the persons based on short stories. In advantageous decisions in daily life and in occupational
addition, he was not able to discriminate between social situations. Therefore, the authors conclude that a deficit
behaviors that would lead to social discomfort or violence. in emotion recognition alone (happiness and anger) does
It was concluded that failure in recognizing specific emo- not account for this behavior. His disinhibitory behavior is
tional expression, which strongly overestimates the con- explained in terms of an impaired ‘social response rever-
sequences of risks in social situations including deficits in sal’ system.
attributing emotions to others, is associated with decline In sum, not recognizing specific emotions, especially
in social behavior. Antisocial behavior is due to impaired happiness and anger, is more associated with socially
‘social response reversal system’, more specifically, the deviant behavior. ToM was not found to be related to
authors conclude that dysfunction of the ‘social response behavioral changes. Three studies explain deviant behav-
reversal system’ is a consequence of insensitivity to disap- ior in terms of the ‘social response reversal’ hypothesis. In
proving social cues (Blair and Cipolotti, 2000). all four studies, the patients showed an overall good per-
Using four types of ToM tasks (Umeda et al., 2010), formance on standard neuropsychological tests, includ-
including first- and second-order false belief, and advanced ing executive functions.
ToM tasks, including the faux pas test, two patients with
characteristics of autism, with both right and left OFC
damage, were examined. Both patients reported a decline
in spontaneous communication with others, having Discussion
social problems in everyday life (Umeda et al., 2010). Both
patients scored within the normal range on standard neu- The goal of the present review was to examine the rela-
ropsychological test, including executive tests. The authors tionship between the cognitive deficits on the tests sug-
only found mild difficulties on the more advanced ToM gested by Zald (e.g., reversal learning task, gambling
task in one patient with a left ventromedial lesion. In this tasks, tasks on social processing and ToM) and behavioral
specific case, the somewhat lower but normal scores on changes following orbitofrontal lesions. The recent find-
the delayed recall on the WMS-R could account for the low ings suggest the following:
score on the advanced ToM task. The patient had some dif- 1. Deficits in reversal learning and recognition of
ficulty in remembering exact story contents. On the Autism- expressed emotions are related to behavioral changes
Spectrum Quotient (AQ) q ­ uestionnaire both cases showed following OFC damage. This is consistent with
a major problem on the social interaction subscale. The the view that a separate (neuro-)cognitive system
authors conclude that the observed mild ToM impairments causes profound emotional and social behavioral
alone do not explain all social interaction deficits. Notably, changes following orbitofrontal cortex lesions (Rolls
both patients recognized a faux pas in the stories contain- et al., 1994; Blair and Cipolotti, 2000; Mitchell et al.,
ing no faux pas. This could not be explained as being due 2006a,b). We found that deficits in reversal learning
to perseveration errors on the WCST. They suggest that might be associated with ‘behavioral disinhibition’,
overcompensation (i.e., one amplifies the opposite behav- and deficits in recognition of emotions might be asso-
ior to compensate for a deficit) might explain the insensi- ciated with ‘rigid or antisocial behavior’. In two stud-
tivity to the recognition of a faux pas and therefore some ies (Blair and Cipolotti, 2000; Mitchell et al., 2006a),
of the behavioral problems. They also cautiously conclude we did not find any deficits on the reversal learning
that the right ventral part of the OFC has been associated task. From an anatomical point of view, a possible
with deficits on the ToM, whereas the left ventral part of explanation for this discrepancy could be the crude
the OFC might be related to social behavioral components way (e.g., CT, MRI, SPECT) of describing the orbito-
(Umeda et al., 2010). frontal lesion in the studies reviewed here. Studies
In contrast, no clear relationship is found between show that impairment on the reversal learning task
impairment of recognition of emotions in a case study in both humans and animals is more associated with
with a traumatic bilateral orbitofrontal lesion and marked the medial part of the OFC (Izquierdo, 2004; Blair,

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior 7

2007; Fellows and Farah, 2007), whereas the lateral ToM test (Stuss and Levine, 2002; Geraci et al., 2010;
part of the OFC is more involved in recognizing inap- Leopold et al., 2012). A possible explanation for this
propriate social behavior and emotional regulation discrepancy, as mentioned earlier, is the crude way
(Blair and Cipolotti, 2000). In a recent study, it was of describing the orbitofrontal lesion, as the prefron-
concluded that Brodmann area 11, a major part of the tal cortex can be divided in three different regions: a
OFC in humans and animals (Anderson et al., 2006; dorsolateral region, a orbitofrontal region, and the
Rudebeck and Murray, 2011b), is not critical for rever- anterior cingulate region (Cummings, 1995). The orbit-
sal learning (Bachevalier et al., 2011; Rudebeck and ofrontal region can be subdivided into medial, ven-
­Murray, 2011b). In the case studies reviewed here, tral, and lateral parts (Moll et al., 2008). In the studies
no subregions or Brodmann areas were mentioned, reviewed, the term ‘OFC’ refers to the combination of
whereas, in addition, the location of lesions (four the medial and ventral regions of the prefrontal cor-
patients bilaterally and two right and one left orbito- tex, given the fact that the medial and ventral regions
frontal damage) shows no distinctive influence on are highly interconnected and anatomically difficult
both reversal learning and ToM tasks. to distinguish (Fellows, 2007). Another explanation
From a functional point of view, it has been sug- might be that most ToM tasks, in the studies reviewed,
gested that the OFC stores an accumulated reward are story based. One must detect socially inappropri-
history, based on positive and negative reinforce- ate behavior, a task that appeals more to cognitive
ment, which estimates the outcome and value of functions (Blair and Cipolotti, 2000) instead of affec-
an (social) action (Fellows and Farah, 2005, 2007). tive aspects. It is suggested that a distinction should be
The inability to change behavior after orbitofrontal made between ‘cognitive’ and ‘affective’ ToMs, which
damage might be a consequence of an inability to are both differently organized in the brain (Blair and
change specific reinforcement patrons, based on the Cipolotti, 2000; Shamay-Tsoory et al., 2005). Damage
individual reward history (Fellows and Farah, 2007; to the VMPFC reflects the more affective aspects of
Wallis, 2007) as reflected by deficits on reversal learn- ToM (Shamay-Tsoory et al., 2006; Shamay-Tsoory and
ing. Others propose the ‘social response reversal’ Aharon-Peretz, 2007; Leopold et al., 2012).
hypothesis, which states that there is a system that 3. Complex higher-order cognitive functions in which
modulates behavior when faced with disapproving the OFC plays a role, such as learning and adapting
social cues (Blair and Cipolotti, 2000), i.e., negative to changing reinforcement contingencies, decision-
emotions, and identifying and responding to socially making and social processing, and ToM, do not coin-
inappropriate behavior (Blair and Cipolotti, 2000; cide with standard neuropsychological functions.
Mitchell et al., 2006a,b). According to this hypoth- Much of what is known about neuropsychology is
esis, the inability to recognize specific expressed based on patients with dorsolateral prefrontal cortex
emotions, particularly expressions depicting anger, dysfunctions, which is involved mainly in cognitive
might disrupt stimulus-associated motor responses, functions, in particular executive functions (Duffy
under the influence of the amygdala, which may lead and Campbell, 1994; Stuss and Levine, 2002). The
to rigid behavior (Fellows and Farah, 2007; Namiki results presented here suggest that deficits on reversal
et al., 2008). Hence, in most cases, the patients were learning tasks and recognition of expressed emotion
well aware that their behavior was not appropriate are indeed differently localized in the brain, consid-
but could not suppress their behavior. This asymme- ering that in all studies referred in this review, no
try between ‘knowing how to behave’ and ‘behaving impairment was found on standard neuropsychologi-
in an inappropriate way’ is also seen in studies on cal functions.
psychopathy with antisocial behavior and is closely 4. The IGT seems to have components of reversal learn-
related to morality (Slachevsky et al., 2006). A large ing (Mitchell et al., 2006a). This suggests that the IGT
difference has been found between an individual’s is a complex instrument that taps several cognitive
ability to be morally competent and morally perform- processes (Bechara et al., 1999; Busemeyer and Stout,
ing, underlining that these processes are indeed sub- 2002). The negative score on the IGT was found to
served by different brain regions (Moll et al., 2008). be related to a mixture of behavioral characteristics
2. No deficits were found on the different ToM tests (compulsively collecting items, antisocial behavior,
following orbitofrontal damage. This is in contrast random purchases). Overall, one could say that this
to neuroimaging studies that report a relationship type of behavior might be classified as ‘impulse con-
between lesions in the OFC and impairment on the trol disorder’. The IGT is designed to assess real-life

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
8 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior

decision making and is said to be sensitive to (right) studies, and there is no information on the validity or
VMPFC damage (Bechara et al., 1994). In line with the reliability of most of these measures. Based on the most
original work of Bechara et al. (1994), which incor- frequently used terms to ‘capture’ behavioral changes fol-
porated patients with relatively extensive bilateral lowing OFC, we have clustered the behavioral disorders in
lesions, we also found that most patients had pre- three clinically based concepts: disinhibition, antisocial-
dominantly bilateral orbitofrontal injury. We describe rigid behavior, and impulse control disorder. We are well
one study with a small orbitofrontal lesion and no aware that these three categories are arbitrary, consider-
deficits on the IGT (Namiki et al., 2008), which is in ing that all terms refer to the inability to control or change
line with Manes et al. (2002), who showed that small behavior.
unilateral lesions restricted to the OFC has no effect
on the IGT. The fact that patients with orbitofrontal
damage tend to make socially inappropriate decisions Conclusion
while rationally aware of possible negative future
consequences of their actions might be influenced by Given the heterogeneous and complex nature of pro-
the reversal learning components of the IGT (Manes cesses subserved by the OFC, results from both animal
et al., 2002; Berlin et al., 2005; Fellows, 2007). This is and human experimental studies suggest that the main
emphasized in a study where they found no difference function of the OFC is (rapidly) processing and select-
between patients with dorsolateral prefrontal damage ing the probable reward value of stimuli in a changeable
and those with ventromedial prefrontal damage on environment (Blair and Cipolotti, 2000; Mitchell et al.,
the IGT (Fellows and Farah, 2005). They conclude that 2006a; Rushworth et al., 2007; Kazama and Bachevalier,
an impaired score on the IGT of ventromedial patients 2009; Rudebeck and Murray, 2011a,b; Rudebeck et al.,
is explained by an underlying reversal learning defi- 2013). Given the result of our review, one could conclude
cits. Studies showed that both patients with amyg- that the suggested clinical tests by Zald measure subcom-
dala damage and those with ventral medial prefrontal ponents of this complex stimulus reinforcement process.
damage performed abnormally on the IGT (Bechara The development of an validated clinical task, a task
et al., 1999). that measures the value of stimulus-reinforcement-out-
come processes, would strengthen the relationship with
the behavioral changes following orbitofrontal damage
(Rushworth et al., 2007; Walton et al., 2011).
Limitations
This study has several limitations. (a) Most of the studies Recommendations
are case studies (n = 1), or studies with low sample size (n),
consist predominantly of men, and with large differences The results of this review suggest that behavioral changes
in the length of time after the lesion (6 months to 42 years) following orbitofrontal lesions are related to cognitive
and differences in age (31–75 years). (b) To establish the dysfunctions, as suggested Zald and Andreotti (2010), and
extent and location of the orbitofrontal lesion, different not sensitive to standard neuropsychological tests. We
neuroimaging methods (CT scan, MRI, SPECT) have been therefore recommend that the different reversal learning
used (Rolls et al., 1994; Hahm et al., 2001; Namiki et al., (based on animal research) and recognition for expressed
2008; Poletti et al., 2010), which could account for the emotions tests should be first tested on psychometric prop-
discrepancy in our findings. In addition, this review and erties for prefrontal lobe dysfunctions in a Dutch popula-
other studies (Umeda et al., 2010) show that using the MRI tion. Second, we recommend neuroimaging for diagnostic
revealed (Shamay-Tsoory and Aharon-Peretz, 2007) more purposes and administration of the tests described here
lesions compared with CT. (c) The substantial differences (reversal learning test, recognition of expressed emotion
in test administration of the reversal learning (Blair and test, and IGT) in case of severe behavioral changes caused
Cipolotti, 2000; Rolls, 2000; Berlin et al., 2004) and social by supposed brain damage and in the absence of execu-
cognition tests (Mitchell et al., 2006a; Umeda et al., 2010) tive deficits (Spikman et al., 2013).
might have influenced the results. The absence of reliable To significantly increase the understanding of the
data or any psychometric data for these various test ver- OFC in relation to behavioral disorders, future studies
sions makes it difficult to interpret the findings. (d) The should involve large numbers of patients with well-
measures of real-world behavior are very variable across defined lesions in the orbitofrontal region and integrate

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior 9

different tasks that measure responses to changing Duffy, J.D. and Campbell, J.J. (1994). The regional prefrontal syn-
stimulus-reward contingencies, neuroimaging, neuro- dromes: a theoretical and clinical overview. J. Neuropsychiatry
Clin. Neurosci. 6, 379–387.
physiology, and structural behavioral measures (Zald and
Fellows, L.K. (2007). The role of orbitofrontal cortex in decision making:
Andreotti, 2010). a component process account. Ann. NY Acad. Sci. 1121, 421–430.
Fellows, L.K. and Farah, M.J. (2005). Different underlying impair-
Acknowledgments: F.A.J. would like to express his deep ments in decision-making following ventromedial and dorsolat-
gratitude to E.J.A. Scherder, C. Jonker, and P. Scheltens, eral frontal lobe damage in humans. Cereb. Cortex 15, 58–63.
Fellows, L.K. and Farah, M.J. (2007). The role of ventromedial pre-
his research supervisors, for their patient guidance,
frontal cortex in decision making: judgment under uncertainty
enthusiastic encouragement, and critical revision of the or judgment per se? Cereb. Cortex 17, 2669–2674.
manuscript for important intellectual content. He would Floris, G., Cannas, A., Melis, M., Solla, P., and Marrosu, M.G. (2008).
also like to thank GGZ Altrecht, Vesalius Centre for Neu- Pathological gambling, delusional parasitosis and adipsia as
ropsychiatry; Department of Clinical Neuropsychology, a post-haemorrhagic syndrome: a case report. Neurocase 14,
VU University; Alzheimer Centre and Department of Neu- 385–389.
Frith, U. and Frith, C.D. (2003). Development and neurophysiology of
rology, VU University Medical Center for their financial
mentalizing. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 358, 459–473.
supporter on this research project. Fujii, T., Suzuki, M., Suzuki, K., Ohtake, H., Tsukiura, T., and
Miura, R. (2005). Normal memory and no confabulation after
extensive damage to the orbitofrontal cortex. J. Neurol. Neuro-
surg. Psychiatry 76, 1309–1310.
References Funayama, M., Mimura, M., Koshibe, Y., and Kato, Y. (2010). Squalor
syndrome after focal orbitofrontal damage. Cogn. Behav.
Anderson, S.W., Barrash, J., Bechara, A., and Tranel, D. (2006). Neurol. 23, 135–139.
Impairments of emotion and real-world complex behavior Geraci, A., Surian, L., Ferraro, M., and Cantagallo, A. (2010). Theory
following childhood- or adult-onset damage to ventromedial of Mind in patients with ventromedial or dorsolateral prefrontal
prefrontal cortex. J. Int. Neuropsychol. Soc. 12, 224–235. lesions following traumatic brain injury. Brain Inj. 24, 978–987.
Bachevalier, J., Machado, C.J., and Kazama, A. (2011). Behavioral Grace, J., Stout, J.C., and Malloy, P.F. (1999). Assessing frontal lobe
outcomes of late-onset or early-onset orbital frontal cortex behavioral syndromes with the frontal lobe personality scale.
(areas 11/13) lesions in rhesus monkeys. Ann. NY Acad. Sci. Assessment 6, 269–284.
1239, 71–86. Hahm, D.S., Kang, Y., Cheong, S.S., and Na, D.L. (2001). A com-
Baron-Cohen, S., O’Riordan, M., Stone, V., Jones, R., and Plaisted, pulsive collecting behavior following an A-com aneurysmal
K. (1999). Recognition of faux pas by normally developing chil- rupture. Neurology 56, 398–400.
dren and children with Asperger syndrome or high-functioning Hanna-Pladdy, B. (2007). Dysexecutive syndromes in neurologic
autism. J. Autism Dev. Disord. 29, 407–418. disease. J. Neurol. Phys. Ther. 31, 119–127.
Bechara, A., Damasio, A.R., Damasio, H., and Anderson, S.W. (1994). Izquierdo, A. (2004). Bilateral orbital prefrontal cortex lesions in
Insensitivity to future consequences following damage to rhesus monkeys disrupt choices guided by both reward value
human prefrontal cortex. Cognition 50, 7–15. and reward contingency. J. Neurosci. 24, 7540–7548.
Bechara, A., Damasio, H., Damasio, A.R., and Lee, G.P. (1999). Differ- Kazama, A. and Bachevalier, J. (2009). Selective aspiration or
ent contributions of the human amygdala and ventromedial pre- neurotoxic lesions of orbital frontal areas 11 and 13 spared
frontal cortex to decision-making. J. Neurosci. 19, 5473–5481. monkeys’ performance on the object discrimination reversal
Berlin, H.A., Rolls, E.T., and Kischka, U. (2004). Impulsivity, time task. J. Neurosci. 29, 2794–2804.
perception, emotion and reinforcement sensitivity in patients Leopold, A., Krueger, F., dal Monte, O., Pardini, M., Pulaski, S.J.,
with orbitofrontal cortex lesions. Brain 127(Pt 5), 1108–1126. Solomon, J., and Grafman, J. (2012). Damage to the left ventro-
Berlin, H.A., Rolls, E.T., and Iversen, S.D. (2005). Borderline person- medial prefrontal cortex impacts affective theory of mind. Soc.
ality disorder, impulsivity, and the orbitofrontal cortex. Am. J. Cogn. Affect. Neurosci. 7, 871–880.
Psychiatry 162, 2360–2373. Manes, F., Sahakian, B., Clark, L., Rogers, R., Antoun, N., Aitken, M.,
Blair, R.J.R. (2007). Dysfunctions of medial and lateral orbitofrontal and Robbins, T. (2002). Decision-making processes following
cortex in psychopathy. Ann. NY Acad. Sci. 1121, 461–479. damage to the prefrontal cortex. Brain 125(Pt 3), 624–639.
Blair, R.J. and Cipolotti, L. (2000). Impaired social response rever- Mitchell, D.G.V., Avny, S.B., and Blair, R.J.R. (2006a). Divergent patterns
sal. A case of “acquired sociopathy”. Brain 123, 1122–1141. of aggressive and neurocognitive characteristics in acquired
Busemeyer, J.R. and Stout, J.C. (2002). A contribution of cognitive deci- versus developmental psychopathy. Neurocase 12, 164–178.
sion models to clinical assessment: decomposing performance Mitchell, D.G.V., Fine, C., Richell, R.A., Newman, C., Lumsden, J.,
on the Bechara gambling task. Psychol. Assess. 14, 253–262. Blair, K.S., and Blair, R.J.R. (2006b). Instrumental learning and
Cohen, L., Angladette, L., Benoit, N., and Pierrot-Deseilligny, C. relearning in individuals with psychopathy and in patients
(1999). A man who borrowed cars. Lancet 353, 34. with lesions involving the amygdala or orbitofrontal cortex.
Cummings, J.L. (1995). Anatomic and behavioral aspects of frontal- Neuropsychology 20, 280–289.
subcortical circuits. Ann. NY Acad. Sci. 769, 1–13. Moll, J., De Oliveira-Souza, R., and Zahn, R. (2008). The neural basis
Damasio, A.R. (1994). Descartes’ error and the future of human life. of moral cognition: sentiments, concepts, and values. Ann. NY
Sci. Am. 271, 144. Acad. Sci. 1124, 161–180.

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
10 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior

Namiki, C., Yamada, M., Yoshida, H., Hanakawa, T., Fukuyama, H., Shamay-Tsoory, S.G., Tomer, R., Berger, B.D., Goldsher, D., and
and Murai, T. (2008). Small orbitofrontal traumatic lesions Aharon-Peretz, J. (2005). Impaired “affective theory of mind” is
detected by high resolution MRI in a patient with major behav- associated with right ventromedial prefrontal damage. Cogn.
ioural changes. Neurocase 14, 474–479. Behav. Neurol. 18, 55–67.
Ogai, M., Iyo, M., Mori, N., and Takei, N. (2005). A right orbitofron- Shamay-Tsoory, S.G., Tibi-Elhanany, Y., and Aharon-Peretz, J.
tal region and OCD symptoms: a case report. Acta Psychiatr. (2006). The ventromedial prefrontal cortex is involved in under-
Scand. 111, 74–76; discussion 76–77. standing affective but not cognitive theory of mind stories.
Poletti, M., Lucetti, C., and Bonuccelli, U. (2010). Out-of-control Soc. Neurosci. 1, 149–166.
sexual behavior in an orbitofrontal cortex-damaged elderly Slachevsky, A., Peña, M., Pérez, C., Bravo, E., and Alegría, P. (2006).
patient. J. Neuropsychiatry Clin. Neurosci. 22, E7. Neuroanatomical basis of behavioral disturbances in patients
Reid-Arndt, S.A., Nehl, C., and Hinkebein, J. (2007). The Frontal with prefrontal lesions. Biol. Res. 39, 237–250.
Systems Behaviour Scale (FrSBe) as a predictor of community Spikman, J.M., Milders, M.V., Visser-Keizer, A.C., Westerhof-Evers,
integration following a traumatic brain injury. Brain Inj. 21, H.J., Herben-Dekker, M., and van der Naalt, J. (2013). Deficits
1361–1369. in facial emotion recognition indicate behavioral changes and
Rolls, E.T. (2000). The orbitofrontal cortex and reward. Cereb. Cortex impaired self-awareness after moderate to severe traumatic
10, 284–294. brain injury. PloS One 8, e65581.
Rolls, E.T., Hornak, J., Wade, D., and McGrath, J. (1994). Emotion- Stone, V.E., Baron-Cohen, S., and Knight, R.T. (1998). Frontal
related learning in patients with social and emotional changes lobe contributions to theory of mind. J. Cogn. Neurosci. 10,
associated with frontal lobe damage. J. Neurol. Neurosurg. 640–656.
Psychiatry 57, 1518–1524. Stuss, D.T. and Levine, B. (2002). Adult clinical neuropsychology:
Rudebeck, P.H. and Murray, E.A. (2011a). Balkanizing the primate lessons from studies of the frontal lobes. Annu. Rev. Psychol.
orbitofrontal cortex: distinct subregions for comparing and 53, 401–433.
contrasting values. Ann. NY Acad. Sci. 1239, 1–13. Umeda, S., Mimura, M., and Kato, M. (2010). Acquired personal-
Rudebeck, P.H. and Murray, E.A. (2011b). Dissociable effects of ity traits of autism following damage to the medial prefrontal
subtotal lesions within the macaque orbital prefrontal cortex cortex. Soc. Neurosci. 5, 19–29.
on reward-guided behavior. J. Neurosci. 31, 10569–10578. Volle, E., Beato, R., Levy, R., and Dubois, B. (2002). Forced collec-
Rudebeck, P.H., Saunders, R.C., Prescott, A.T., Chau, L.S., and Mur- tionism after orbitofrontal damage. Neurology 58, 488–490.
ray, E.A. (2013). Prefrontal mechanisms of behavioral flexibility, Wallis, J.D. (2007). Orbitofrontal cortex and its contribution to
emotion regulation and value updating. Nat. Neurosci. 16, decision-making. Annu. Rev. Neurosci. 30, 31–56.
1140–1145. Walton, M.E., Behrens, T.E.J., Noonan, M.P., and Rushworth, M.F.S.
Rushworth, M.F.S., Behrens, T.E.J., Rudebeck, P.H., and Walton, M.E. (2011). Giving credit where credit is due: orbitofrontal cortex
(2007). Contrasting roles for cingulate and orbitofrontal cortex in and valuation in an uncertain world. Ann. NY Acad. Sci. 1239,
decisions and social behaviour. Trends Cogn. Sci. 11, 168–176. 14–24.
Shamay-Tsoory, S.G. and Aharon-Peretz, J. (2007). Dissociable Zald, D.H. and Andreotti, C. (2010). Neuropsychological assessment
prefrontal networks for cognitive and affective theory of mind: of the orbital and ventromedial prefrontal cortex. Neuropsycho-
a lesion study. Neuropsychologia 45, 3054–3067. logia 48, 3377–3391.

Cees Jonker received his graduation as neurologist in 1975 and spe-

F.A. Jonker recieved his master of arts (MA) in 2000 in clinical
cialized in behavioral neurology. He became a staff member on a
psychology. He became a general mental healthcare psychologist
neuropsychiatric institute, after that he was appointed at the Alzhei-
(GZ-psychologist) in 2006. From 2008 he worked in a mental health
mer Center at the VU University. In 1986 he defended his PhD thesis
institute for neuropsychiatry (Vesalius), sub-department of mental
on Senile Dementia on Alzheimertype. From 1989–1994 he was
health institute Altrecht (the Netherlands). He became a specialist
scientific director of the Amsterdam Study on the Elderly (AMSTEL),
in clinical neuropsychology in 2012 and is head of the department.
a large-scale population-based study on cognitive decline and
Since 2013 he is also is a researcher at the VU University Amster-
dementia. From 1995 he was associate professor at the LASA study
dam (the Netherlands), department of Clinical Neuropsychology,
and in 2001 he was appointed a professor in Diagnosis and Treat-
specialist on the interaction between brain injury and behavior.
ment of Dementia. He was honoured for his scientific work by the
Dutch Psychiatric Association in 1987.

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM
 F.A. Jonker et al.: Role of the orbitofrontal cortex in cognition and behavior 11

Philip Scheltens received his MD in 1984 at VU University and Erik Scherder is head of the department clinical Neuropsychol-
became a staff neurologist in 1991. He defended his PhD thesis on ogy and full professor at the VU University Amsterdam (the
MRI in Alzheimer’s disease in 1993 and was appointed a Professor ­Netherlands). Furthermore he is full professor for Human Move-
of Cognitive Neurology in 2000. From that time on he led the Alzhei- ment Sciences at the Rijksuniversiteit Groningen (the Netherlands).
mer Center which grew into the largest in the Netherlands under his ­Currently, he is conducting research on pain experience in people
leadership in terms of patient care and research. He was honored with neurodegenerative diseases.
with a membership of the Royal Academy of Arts and Sciences in
2011.

Brought to you by | HEC Bibliotheque Maryriam ET J.

Authenticated
Download Date | 6/7/15 9:33 PM