Brain and Cognition 50 (2002) 414431

www.academicpress.com

Neuroimaging of emotion and personality:

Scientific evidence and ethical considerations
Turhan Canli* and Zenab Amin
SUNY Stony Brook, Stony Brook, NY 11794, USA
Accepted 1 July 2002

Abstract

Affective neuroscience has seen an explosion of research efforts using modern neuroimaging
approaches to uncover the neural basis of emotion and personality. The first section of this
paper reviews studies from the domains of affective and forensic neuroimaging. These studies
illustrate some of the topics likely to be the subject of future ethical debates. The second
section relates limitations of the neuroimaging approach to ethical considerations in predicting
future psychopathology on the basis of brain state analysis.
! 2002 Elsevier Science (USA). All rights reserved.

1. Introduction

There has always been a fascination with how the brain is related to the human
experience. How does it make us human, endow us with reason, emotion, and
personality? The curious of the late 1840s were given a glimpse at the answer when
they read about the fate of Phineas Gage in the medical journals of the time. Gage
was a railway construction worker who survived a catastrophic accident while
working with an iron rod and explosives: an unintended blast turned the rod into a
projectile that pierced his skull, entering through the jaw, past the left eye, through
ventromedial prefrontal regions of his brain and out of the top of his skull (see Fig.
1). Through it all, he remained conscious and was able to relay the details of his
misfortune to his fellow workers and to medical professionals. Two things made his
case remarkable: first, he survived and second, the changes brought on by his injury
did not affect his cognitive capabilities (e.g., speech and vision, save for the loss of his
left eye), but did profoundly alter his personality and emotional behavior. The ac-
cident changed Mr. Gage from a courteous, well-liked, socially proper, and com-
petent manager with good executive skills to an uninhibited, rude, and impatient
person who was unable to plan for the future (Damasio, 1994). Was this change in
personality specific to the location of the injury or simply an individual!s response to
a life-altering, traumatic experience? This question cannot be answered on the basis
of any case study and is best addressed using a functional neuroimaging approach in
persons with intact brains.

*
Corresponding author. Fax: 1-631-632-7876.
E-mail address: turhan.canli@sunysb.edu (T. Canli).

0278-2626/02/$ - see front matter ! 2002 Elsevier Science (USA). All rights reserved.
PII: S 0 2 7 8 - 2 6 2 6 ( 0 2 ) 0 0 5 1 7 - 1
 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431 415

Fig. 1. Phineas Gage. Left panel shows picture of Phineas Gage!s skull. Right panel shows computer
reconstruction of the most likely path of the rod though Gage!s brain. Reprinted with permission from Dr.
Hannah Damasio.

The development of functional brain imaging techniques such as functional

magnetic resonance imaging (fMRI) and positron emission tomography (PET) al-
lows for replicable experimental designs to investigate the relation between brain
function and emotion and personality in individuals without such catastrophic brain
injuries. Such research efforts are reviewed in the first section of this paper, which
highlights research on emotion and personality in normal, healthy individuals (af-
fective neuroimaging) and in violent, psychopathic individuals (forensic neuroi-
maging). These research areas are concerned with the biological basis of socially
relevant issues, such as racial attitudes or violent behavior. Early advances in these
fields give hope that it may be possible to develop new approaches to the prevention
or treatment of social ills. At the same time, serious ethical concerns can arise when
neuroimaging methods are naively accepted as providing an objective description of
a person!s brain state, particularly as it relates to predicting future behavior. The
second part of this paper will therefore discuss limitations of the neuroimaging
approach. A realistic understanding of the neuroimaging approach is critical to find
a judicious and ethical balance between the needs and rights of the individual against
those of society.

2. Two domains of neuroimaging of emotion and personality: Affective and forensic

neuroimaging

Interest in the biological basis of emotion and personality has greatly increased in
the past decade. A literature search in PubMed shows that the number of publica-
tions with the terms emotion and brain has more than doubled between 1995
and 2000 (see Fig. 2). Much of this growth comes from neuroimaging studies, which
were, in part, inspired by the pioneering and elegant animal work on the neural basis
of fear (Aggleton, 2000) and further catalyzed by methodological advances in
functional brain imaging techniques. Neuroimaging studies of emotion have inves-
tigated the neural basis of emotional recognition, experience, memory, regulation,
and individual differences in the human brain. A burgeoning interest in social
neuroscience (Cacioppo, Berntson, Sheridan, & McClintock, 2000; Ochsner &
Lieberman, 2001) underscores the belief that neuroscience can make contributions to
the understanding of social issues.
Excellent summaries of the accomplishments in affective neuroscience are avail-
able elsewhere (Allman, Hakeem, Erwin, Nimchinsky, & Hof, 2001; Davidson,
416 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431

Fig. 2. Number of publications on emotion. Using the keyword emotion and brain, a Medline
literature search was conducted for the time period from 1980 to 2000.

Pizzagalli, Nitschke, & Putnam, 2002; Davis & Whalen, 2001; Drevets, 2000; Le-
Doux, 2000). Here, we will highlight studies from two domains that will likely
provide scientific commentary for future controversies: (1) Affective neuroimaging
studies of emotion and personality in healthy individuals; and (2) forensic neuroi-
maging studies of violent individuals. These research areas are of particular interest
because many controversial subjects are, at their core, about the biological basis of
emotions and individual differences. For instance, debates regarding the criminal
justice system often revolve around the question of whether people can change, and
whether there is a biological determinism that causes some individuals to be anti-
social, violent, or psychopathic. Are some people incapable of controlling their
emotions, impulses, or urges? Should they be held responsible for their actions?
Another example is racism, where the significance of unconscious bias lies at the
center of many debates over racial attitudes. Therefore, work on the biological
mechanisms of emotion and individual differences is likely going to be relevant in the
future of these debates.

2.1. Affective neuroimaging: Emotion and personality in healthy individuals

Before we discuss work on violent individuals, let us focus on what is known

about emotional processes and personality in non-violent, normal, healthy individ-
uals. In this context, we will highlight work on individual differences in emotional
memory and personality, on brain processing of racial information, and on emo-
tional control and insight.

2.1.1. Individual differences in emotional memory and personality

Guided by animal work (Cahill & McGaugh, 1998; Davis, 2000; LeDoux, 2000),
functional imaging studies concerned with emotional memory in humans have fo-
cused on the amygdala. In the first study of its kind, Cahill and colleagues correlated
amygdala activation with subjects! ability to recall neutral or negative emotional film
clips presented during a PET scan three weeks later (Cahill et al., 1996). They found
that those individuals with the greatest amount of glucose metabolism in the
amygdala also had the best memory. Importantly, this correlation only held for
emotional film clips, but not for neutral film clips. Other studies have replicated and
extended this observation to positive emotional stimuli (Canli, Zhao, Desmond,
 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431 417

Glover, & Gabrieli, 1999; Hamann, Ely, Grafton, & Kilts, 1999). These studies share
a between-subjects design that allows for at least two interpretations of the data. One
interpretation is that some subjects may have had constantly activated amygdala
(tonic activation), perhaps due to some trait such as high anxiety. Accordingly, it
is not clear whether enhanced emotional memory is due to amygdala activation or
another factor associated with high anxiety, such as increased attention and vigi-
lance. The other interpretation is that each subject may have exhibited some vari-
ation in amygdala activation on a trial-by-trial basis (phasic activation), such that
stimuli that elicited greater activation would be more likely remembered than stimuli
that elicited less activation.
These two interpretations were explicitly tested in a subsequent within-subject,
event-related fMRI study (Canli, Zhao, Brewer, Gabrieli, & Cahill, 2000). Amygdala
activation was reported to vary on a trial-by-trial basis, such that pictures experi-
enced as more emotionally arousing produced greater amygdala activation than
pictures experienced as less arousing, and greater amygdala activation in response to
individual pictures was predictive of better subsequent memory for these specific
pictures. The correlational approach taken by these studies demonstrates that in-
dividual differences in brain reactivity do not necessarily represent noise in the
data, but can instead contain valuable signal that reveals much about the fun-
damental aspects of brain functioning.
This insight has been particularly valuable for work on personality. For instance,
extraversion (E) and neuroticism (N) are two fundamental, independent, dimensions
of human personality that are associated with emotional reactivity (Larsen & Ket-
elaar, 1991; Pervin & John, 1999). Extraverted individuals are susceptible to positive
mood induction, whereas neurotic individuals are susceptible to negative mood in-
duction (Larsen & Ketelaar, 1991). Building on the relation between E and N and
emotional reactivity, Canli and colleagues (Canli et al., 2001) used fMRI to inves-
tigate whether variation in these personality traits would correlate with individual
differences in brain reactivity to positive and negative emotional stimuli, respectively.
Participants were scanned while they passively watched alternating blocks of positive
and negative scenes. Changes in blood-level oxygenation in response to these emo-
tional pictures were then correlated with participants! trait measures of E and N. It
was found that brain reactivity to positive (relative to negative) pictures correlated
with E in a number of cortical and subcortical locations, including the amygdala.
Similarly, brain reactivity to negative (relative to positive) pictures correlated with N
in several loci. This study was a useful first step relating measures of trait personality
with emotional brain reactivity. The study was limited, however, in that it lacked a
neutral baseline condition, only included females, and was based on a loosely con-
strained task. Thus, it was not possible to distinguish increased activation to positive
stimuli from decreased activation to negative stimuli, generalize the finding to males,
or ascribe specific cognitive functions to the loci reported in the study.
A second study (Canli, Sivers, Gotlib, & Gabrieli, 2002) used a more constrained
task (gender discrimination of pictures of faces), both sexes and a neutral baseline
condition. This study was further strengthened by testing, a priori, the prediction by
Canli et al. (2001) that amygdala activation to happy faces should correlate with
extraversion. This prediction was confirmed (see Fig. 3): amygdala activation to
happy, relative to neutral, faces correlated with the personality trait of extraversion,
but not other, unrelated, personality traits. Importantly, this relation was specific to
happy faces, because amygdala activation to other emotional facial expressions did
not correlate significantly with this trait.
It should be noted that the neural correlates of personality are not limited to
emotion-related processes, but have also been reported for non-emotional cognitive
processing and brain activation at rest (Ebmeier et al., 1994; Fischer, Wik, &
Fredrikson, 1997; Haier, Sokolski, Katz, & Buchsbaum, 1987; Johnson et al., 1999;
418 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431

Fig. 3. Amygdala activation to happy faces as a function of extraversion. Left panel shows an axial cut
through the region of the amygdala. Correlation cluster (in white) was located at )22, )9, )20. Right panel
shows scatterplot for amygdala activation to happy versus neutral faces as a function of extraversion
scores for the 15 participants of the study. A scatterplot was generated from participants! mean activation
(in T scores) within the amygdala region-of-interest from voxels that survived small volume correction
(height: p < :05, corrected; extent: 5 voxels). Black squares represent females, black triangles represent
males.

Stenberg, Risberg, Warkentin, & Rosen, 1990, 1993; Sugiura et al., 2000). Although
the use of a rest condition has recently been questioned as an appropriate control
condition (Gusnard & Raichle, 2001), these studies suggest that the neural basis of
personality may be manifested in a number of different affective and cognitive
processes.

2.1.2. Brain processing of racial information

Three fMRI studies have investigated the brain basis of processing racial aspects
of faces.1 Hart and colleagues (Hart et al., 2000) used fMRI to scan subjects who
identified themselves as White or Black, as they viewed photographs of White and
Black faces. The investigators found that subjects responded with stronger amygdala
activation to faces of the other race (outgroup) than the same race (ingroup) as
themselves. A major contribution of the study was the discovery of differential
temporal dynamics in amygdala activation to these two classes of stimuli. Specifi-
cally, amygdala activation to faces habituated to repeated presentations of ingroup
but not outgroup faces. Indeed, initial amygdala activation to these two stimuli types
did not significantly differ in the first half of the scan. This study should be regarded
as preliminary, however, because only eight subjects (half male, equal number of
Black and White subjects) participated, leaving too few degrees of freedom to
control for gender and race-specific effects.
The unconscious processing of racial information was the focus of a study by
Phelps and colleagues (Phelps et al., 2000). White subjects were scanned while they
viewed pictures of unfamiliar White or Black faces. Brain activation was correlated
with both implicit and explicit measures of race evaluation. Phelps and colleagues
reported a significant correlation between amygdala activation to unfamiliar Black
(relative to White) faces and implicit measures (Implicit Association Test and Po-
tentiated Startle) of race evaluation. Importantly, no such correlation was found
when an explicit measure was used (the Modern Racism Scale) or when faces of
familiar and positively regarded Black and White persons were used. It was

1
The race labels used in this text are based on the terminology adopted by each of the three studies
reviewed here.
 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431 419

concluded that amygdala activation is related to unconscious social evaluations, but

that activation to social stimuli can be modified by experience. The authors reminded
the reader that correlation does not imply causation and suggested that both be-
havioral and amygdala activation measures may represent learned social evalua-
tions. At the current time, it is unknown to what extent these observations would
replicate in Black subjects.
A third study (Golby, Gabrieli, Chiao, & Eberhardt, 2001) focused on the
question of why humans recognize persons from their own race better than persons
from another race. Ten African-American (AA) and 10 European-American (EA)
subjects were scanned while they viewed unfamiliar AA and EA faces. All subjects
exhibited greater activation, mostly in the right hemisphere, in the fusiform face area
to same-race than to other-race faces. Recognition memory was also better for same-
race faces in EA subjects, and brain activation correlated with better recognition
memory for same-race faces in the left fusiform cortex and right hippocampal and
parahippocampal regions. Future work needs to address why activation to same-race
faces is right-lateralized but memory encoding for the same stimuli is left-lateralized.
Taken together, these studies demonstrate that social psychology and neurosci-
ence can be integrated in a research program based on functional imaging ap-
proaches. Social membership, evaluation, and recognition and encoding processes
related to socially relevant information can be correlated with individual differences
in brain activation. Although the data accumulated so far are preliminary, they
suggest that it may be possible to address social phenomena in terms of individuals!
underlying brain function. On the other hand, correlational data need to be evalu-
ated carefully and do not prove causality. We will return to this caveat in a later
section.

2.1.3. Emotional control and insight

To date, research on emotional control has largely focused on inhibitory control
over negative emotions. Brain regions that are believed to be involved in these
processes include the amygdala and the lateral prefrontal (PFC) and orbitofrontal
(OFC) cortices (Blair & Cipolotti, 2000; Davidson, Jackson, & Kalin, 2000a; Da-
vidson, Putnam, & Larson, 2000b; Mitchell & Blair, 2000; Raine et al., 1998). Patient
studies relate lesions of the OFC and adjacent PFC to impulsive aggression (An-
derson, Bechara, Damasio, Tranel, & Damasio, 1999; Blair & Cipolotti, 2000). In-
duction studies of transient anger are associated with OFC activation, suggesting a
role for this structure in anger regulation (Dougherty et al., 1999; Kimbrell et al.,
1999).
Studies by Davidson and colleagues have specifically focused on emotion regu-
lation (Davidson et al., 2000a, b). When subjects were instructed to suppress their
negative emotions to aversive pictures they showed less startle in response to a
startle-probe than when they were instructed to maintain their negative affect. The
ability to suppress emotions was related to individual differences in left prefrontal
activation. A recent fMRI study by Davidson and colleagues implicated subcortical
regions in emotion regulation (Schaefer et al., 2001). Subjects viewing unpleasant
pictures exhibited greater amygdala activation when they were instructed to main-
tain a negative emotion than when they were instructed to passively view the images.
Thus, both prefrontal cortical and subcortical regions appear to be involved in the
regulation of negative affect.
Two lines of work point to neural systems that may be involved in the ability to
understand emotions in oneself and others. One line is represented by Theory of
mind studies, the other by work on emotional insight. Theory of mind focuses on
people!s ability to attribute mental states to others and to predict and understand
other people!s behavior on the basis of their mental states (Premack & Woodruff,
1978). Individuals with autism, Asperger!s syndrome, and paranoid delusional
420 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431

schizophrenia show severe impairments in theory of mind abilities (Baron-Cohen

et al., 1999; Fletcher et al., 1995; Frith, 1989; Frith & Corcoran, 1996; Happe et al.,
1996). A number of imaging studies have identified medial prefrontal areas as
playing a role in theory of mind tasks. For instance, McCabe and colleagues
(McCabe, Houser, Ryan, Smith, & Trouard, 2001) found that scanned subjects who
played a standard two-person trust and reciprocity game with human and com-
puter counterparts had activation in prefrontal regions only when they attempted
cooperation with their human, but not computer, counterparts. It is fascinating to
note that a subset of participants who showed no behavioral inclination towards
cooperativity did not exhibit significant differences in prefrontal activation between
computer and human conditions. The failure to cooperate with other persons at the
behavioral level of analysis was therefore accompanied by failure of their brains to
register the difference between a human and a non-human opponent. On the other
hand, there are methodological concerns that require additional follow-up work to
replicate this initial report. For example, the number of participants was small (5
non-cooperators, 7 cooperators) and group-level (random effects) analyses are not
appropriate for such small N. Furthermore, there was no discriminant validity check
to test the alternative explanation that brain activation differences between both
groups were due to anything but group differences in cooperativity.
Work on emotional insight is represented by Lane and colleagues who have been
interested in the question of emotional awareness and experience. They reported
(Lane, Fink, Chau, & Dolan, 1997) that activation in a region of the anterior cin-
gulate was only observed when participants focused on their subjective emotional
experience as they viewed complex emotional pictures, but not when they focused on
the visuospatial features of the stimuli. A follow-up study by this group then re-
ported that activation in the same region was correlated with individual differences in
the capacity for emotional awareness (Lane et al., 1998). This study was limited to
female subjects and no alternative questionnaire measures were collected to establish
discriminant validity. Furthermore, one of the tasks confounded emotional experi-
ence with the presentation of facial expressions which were present in the emotional
film condition, but absent in the neutral film condition, and data were collapsed
across three emotion conditions (happy, sad, and disgust). Thus, follow-up work still
needs to determine the relationship between cingulate activation and levels of
emotional awareness for males, and for specific individual emotional states.
The affective imaging studies reviewed here illustrate approaches to investigate the
neural basis of individual differences in the processing of emotional or socially rel-
evant stimuli in normal, healthy individuals. This work is valuable because prior
approaches were mostly limited to brain-damaged patients or animals, or used brain
mapping methods (e.g., electroencephalography, EEG) with limited spatial resolu-
tion. They are also valuable because their methods can be applied to the study of
emotional or personality disorders, as in the example of forensic neuroimaging.

2.2. Forensic neuroimaging: Psychopathic individuals

The violence encountered in American schools and society has many searching for
a preventative silver bullet. Is it possible to use brain imaging approaches to predict
violent behavior before it surfaces? Research efforts are underway that will be rel-
evant for future debates weighing the autonomy of the individual against public
safety. This work, which one could describe as "Forensic Neuroimaging,! aims to
unravel the biological basis of violence and psychopathy.
Some of these studies have focused on individuals whose violent behavior may be
a manifestation of a psychiatric condition (Axis II, DSM-IV; American Psychiatric
Association, 1994) known as antisocial personality disorder (APD). A subset of
persons with APD are described as psychopathic or psychopaths and may be distinct
 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431 421

from the normal population in their incapacity to process emotional signals and feel
empathy, guilt, or remorse. Such individuals can be identified by their extreme scores
on the revised Psychopath Checklist (PCL-R; Hare, 1991). It is estimated that about
75% of the prison population may qualify as APD, of which 25% may be psycho-
paths (Abbott, 2001). One challenge in forensic neuroimaging will be to determine
whether there is a unique neural signature that characterizes APD and psychopathic
individuals.
Related to the categorization of violent persons, violent acts can also be classified
into categories that have different behavioral manifestations. Distinctions can be
made between reactive versus instrumental (Blair, 2001) or affective versus
predatory aggression (Raine et al., 1998). Reactive or affective aggression is ex-
pressed in response to frustration, or a real or perceived threat or provocation. In-
strumental or predatory aggression is unprovoked, goal-directed, and calculating.
The challenge for forensic neuroimaging will be to determine whether and how these
different forms of violence are mediated through different neural circuits.
Blair (2001) has suggested that reactive aggression is mediated through the or-
bitofrontal (OFC) or ventromedial prefrontal cortex, because patients with lesions in
this, but not in other brain regions, display this form of aggression. According to
Blair!s social response reversal model, damage to this region produces reactive ag-
gressive behavior because this region is hypothesized to modify social behavior by
processing social cues that would normally curtail aggressive behavior. Alternatively,
Damasio!s somatic marker hypothesis would explain aggressive behavior in patients
with prefrontal damage in terms of its impaired function to integrate emotional,
visceral information into cognitive decision-making processes (Damasio, 1994).
Consistent with Damasio!s model, patients with damage to the ventromedial
prefrontal cortex (but also in patients with damage to the amygdala; Bechara,
Damasio, Damasio, & Lee, 1999) perform poorly in a laboratory gambling task in
which anticipatory visceral reactions, as measured by skin conductance, appear to
influence cognitive choices (Bechara, Damasio, Tranel, & Damasio, 1997). In con-
trast to healthy subjects, patients prefer a strategy of large short-term gains that
come at the cost of larger long-term losses and fail to develop anticipatory increases
in skin conductance when they contemplate a risky choice in the game. Remarkably,
even when the optimal strategy is revealed to them, they fail to implement it in their
game.
The relevance of the ventromedial prefrontal cortex in the etiology of psychop-
athy is suggested by a study of two patients with early onset ventromedial prefrontal
brain damage (Anderson et al., 1999). Similar to patients with adult-onset damage,
these individuals exhibited normal basic cognitive abilities, but were impaired in the
gambling task. In contrast to adult-onset patients, early onset patients had a history
of disruptive behavior, stealing, physical threats and assaults, and expressed no guilt
or remorse for their behavior. However, the authors noted that the patients! ag-
gressive behavior was impulsive rather than goal-directed (i.e., not instrumental or
predatory) and thus differed from the normative psychopath. In the laboratory,
early onset patients exhibited a marked deficit in several tasks of social knowledge
and moral reasoning, which was interpreted by the authors as indicative of a failure
to learn social and moral norms. This implies that the neural architecture associated
with the acquisition of social knowledge may be dissociable from other neural cir-
cuits. Unfortunately, because early onset prefrontal patients are very rare, it is dif-
ficult to generalize from these two patients.
Additional support for the view that prefrontal regions are concerned with the
processing of moral or social knowledge comes from imaging studies in healthy,
normal, non-violent subjects. One fMRI study had normal volunteers scanned as
they pondered non-moral and moral dilemmas (Greene, Sommerville, Nystrom,
Darley, & Cohen, 2001), For moral dilemmas, there were two types of stimuli: those
422 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431

that had a personal, emotional, component (moralpersonal) and those that did not
(moralimpersonal). The authors reported that moralpersonal dilemmas, relative to
impersonal and non-moral dilemmas, produced significant activation increases in the
medial frontal gyrus, posterior cingulate gyrus, and angular gyrus. The authors in-
terpreted the involvement of these regions to suggest that neural systems associated
with affect were engaged in the personalmoral decision-making process. However,
subjects! emotional reactions were not explicitly measured and some structures
associated with emotional processes (e.g., the amygdala) did not activate in these
tasks.
Another imaging study of healthy, non-violent, normal volunteers compared
brain activation between negative pictures without a moral context (e.g., body le-
sions, dangerous animals) and others with a moral context (e.g., physical assaults,
abandoned children) (Moll et al., 2002). The presence or absence of a moral element
in the picture was verified post-scan by the participants who were otherwise passively
viewing these stimuli. It was reported that moral, relative to non-moral, negative
pictures produced significant activation in prefrontal regions, including medial
frontal gyrus and medial orbitofrontal cortex. The finding that a contrast between
two kinds of highly negative images can produce significant activation differences in
regions associated with moral reasoning or theory-of-mind processes is certainly
remarkable. However, it remains to be shown that the moral aspect of one stimulus
set is the determining factor for this activation pattern. It is possible that other as-
pects of the stimuli sets played a significant role. For example, one stimulus set
(moral-negative) may depict human interactions whereas the other (non-moral-
negative) shows either animals or individual humans without an interactive context.
Nevertheless, the sum of these patient and imaging studies suggests that prefrontal
regions may play an important role in the acquisition or social and moral norms,
moral evaluations or moralemotional reactions.
Imaging studies of accused murderers further implicates prefrontal regions in anti-
social, violent behavior. A PET imaging study of accused murderers assessed the role
of prefrontal dysfunction in violent behavior (Raine et al., 1994). The test group
(murderers) consisted of 22 persons charged with murder or attempted murder
who underwent scanning in the context of an insanity plea or to determine their
competence to stand trial. The investigators were careful to select a control group
(controls) of 22 age- and gender-matched subjects. Of these, three were schizo-
phrenic to match three schizophrenic subjects from the test group and the remaining
subjects were healthy volunteers with no reported history of psychiatric illness, sei-
zure, substance abuse, or head trauma. The authors reported significantly lower
metabolism in the lateral and medial prefrontal cortex of the accused murderers,
relative to controls. These differences have to be interpreted with caution, however,
because the two samples differed in some important aspects. For example, 10 of the
murderers had a history of head injury, compared to none of the controls. Fur-
thermore, a causal link between lowered prefrontal metabolism and violence is dif-
ficult to establish, because both may be the result of other environmental,
developmental or genetic influences.
A follow-up study aimed to identify the neural circuitry associated with predatory
versus affective aggression (Raine et al., 1998). Predatory murderers are defined to
act on purpose and without provocation to achieve a goal, whereas affective mur-
derers are defined to act in response to physical or verbal challenge with uncontrolled
violence. Raine and colleagues compared brain glucose metabolism in 15 predatory
and 9 affective murderers to 41 normal controls. Relative to healthy control vol-
unteers, they reported that both types of murderers had elevated glucose metabolism
in subcortical (hippocampus, amygdala, thalamus, and midbrain) regions, but dif-
fered from each other in cortical regions. Affective murderers had lower prefrontal
metabolism than controls whereas predatory murderers did not differ from controls.
 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431 423

The data were interpreted to show that both types of murderers exhibited higher-
than-normal activation in subcortical regions associated with the generation of ag-
gressive impulses, but that predatory murderers had intact prefrontal systems to
regulate these impulses whereas affective murderers did not. Future studies need to
address alternative interpretations. For example, it is possible that the increased
subcortical activation in both groups of murderers, relative to controls, is the result
of a general arousal state that results from the experience of incarceration. An ad-
ditional control group of prison inmates who are not murderers would address this
concern. Also, the assumption that predatory and affective murderers differ in im-
pulse control was not explicitly tested. The inclusion of a cognitive test of impulse
control should reveal such differences and performance could be correlated with
degree of brain activation. Finally, it is possible that predatory and affective mur-
derers differ in other ways that may be related to developmental, environmental, or
genetic factors. Follow-up work needs to address to what extent prefrontal activa-
tion differences can be attributed to these other factors.
Substantial empirical work in affective neuroscience has identified the amygdala as
a critical structure in the processing of emotionally salient information, emotional
learning and memory, and the processing of facial expressions of emotion (see
above). Consequently, forensic neuroimaging is now addressing to what extent the
amygdala may play a role in violent or psychopathic behavior. According to Blair
(2001), dysfunction of the amygdala is associated with instrumental aggression and
explains why psychopathic individuals have a diminished responsiveness to facial
expressions of sadness and fear and why they do not exhibit fear-potentiated startle.
At the core of the dysfunction, according to Blair, lies the inability to have the
amygdala form associations between human distress cues and violent behavior that
caused the production of these distress cues (Blair, 1995).
Some imaging evidence supports the view that the amygdala is dysfunctional in
violent subjects. In an fMRI study on conditioned aversive emotional responses
(Schneider et al., 2000), Schneider and colleagues found differing activation patterns
between APD subjects and controls when receiving paired presentations of neutral
face pictures and aversive odors. Controls showed decreases and APD subjects in-
creases in amygdala and dorsolateral prefrontal cortex. This finding was interpreted
to illustrate that APD subjects need to exert additional effort to form the same kinds
of emotional associations that normal controls accomplish without effort. However,
effort was not directly measured. An alternative explanation for these differing
activation patterns is that controls and APD subjects form different representations
of the CSUS association or otherwise process stimuli differently.
Amygdala dysfunction, albeit in terms of decreased activation, has also been re-
ported in an fMRI study that compared neural activation to emotional words in
criminal psychopaths, criminal non-psychopaths, and non-criminal controls (Kiehl
et al., 2001). It was reported that criminal psychopaths had significantly less brain
reactivity to negative words in the amygdala, as well as hippocampus, parahippo-
campal gyrus, ventral striatum, and anterior and posterior cingulate, than criminal
non-psychopaths and non-criminal controls. Interestingly, greater activation in this
group, relative to the two control groups, was reported for regions outside the limbic
systems, such as the left superior temporal gyrus and right inferior frontal gyrus.
This finding is consistent with a report by Intrator and colleagues (Intrator et al.,
1997) who found greater activation in psychopaths, relative to controls, to emotional
words in frontaltemporal cortex. Although such increased activation is commonly
interpreted as representing greater processing effort by psychopaths, this interpre-
tation is not explicitly tested. Furthermore, since only language-based stimuli were
used, future work needs to extend these findings to other types of emotional stimuli.
Indeed, the small sample size (N 8 per group) limits the extent to which these
findings can be generalized at this time.
424 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431

2.3. Comments

This review of current work in affective and forensic neuroimaging highlights

research strategies and early findings that are likely to shape the future research
agenda and social, cultural, and political debates. The fact that the conclusions of
any individual study can be softened by alternative interpretations or methodolog-
ical concerns is a useful reminder that the knowledge-base in these domains is
malleable and awaits replication and extension. With this in mind, we will now
discuss in greater detail general limitations of the neuroimaging approach, as it re-
lates to ethical considerations.

3. Ethical considerations and limitations of the neuroimaging approach

Common concerns in biomedical ethics, such as privacy, confidentiality, and

agency, are equally relevant to neuroimaging of emotion and personality. However,
these issues have been contemplated elsewhere (Glannon, 2001). Here, we want to
focus on ethical considerations as they apply uniquely to neuroimaging. This is
important because the greatest concern we have is that exaggerated and naive ex-
pectations about the power of neuroimaging can lead to unethical use of this tech-
nology. Therefore, this section will discuss the limitations of the neuroimaging
approach with respect to three applications: (1) Structural and functional brain
characterization; (2) association between brain state and psychological or behavioral
measures; and (3) prediction of future psychopathology. Each of these applications
has its own set of methodological limitations that relate to ethical concerns.

3.1. Structural and functional brain characterization

An applicant for a life insurance policy may be asked to submit to a structural

brain scan to determine the presence of contra-indications. A defense attorney may
want to demonstrate that her client is incapable to stand trial on account of some
organic brain damage. These are the kinds of scenarios where neuroimaging may be
used to determine whether a person!s brain has some form of pathology.
Although some structural changes (e.g., discrete tumors or lesions) can be un-
ambiguously identified, other structural abnormalities can be much more subtle. In
such cases, one would like to compare a scan image from the individual in question
with a normative template. This can be difficult for three reasons. First of all, there
are few templates of normal brains against which one could compare an individual
sample. Second, it is unclear which brain measure should be used as a normative
standard. Should it be size? If so, should one use overall volume or rather specific
measures of certain brain regions or nuclei? Should it be the ratio of white matter to
grey matter? Neurons to glia? Or should it be the size of the ventricles? There may be
no single measure that can serve as a gold standard. Third, the decision whether a
given sample is normal or pathological is statistical, not absolute. This is be-
cause a normative template would consist of the average multiple brains, so that any
given brain structure is an averaged representation whose shape will vary along a
normal distribution in each dimension. To compare a test sample against the nor-
mative template means to determine whether its measures are significantly different
from the normal distribution. This leads to the fourth and final point. The decision
whether a given brain structure falls within the normative range will likely vary from
one brain structure to another, so that any given brain may qualify as normal by
one measure but not another.
Statistical uncertainty is an even bigger factor when one attempts to characterize
brain function in terms of activation patterns. When one sees an image of a brain!s
 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431 425

activation pattern, it is difficult not to be struck by its visual persuasiveness. How-

ever, the image of an activation pattern from a poorly designed study is visually
indistinguishable from one based on an exemplary study. It takes a skilled practi-
tioner to appreciate the difference. Therefore, one great danger lies in the abuse of
neuroimaging data for presentations to untrained audiences, such as courtroom
juries. What can be easily forgotten when looking at these images is that they rep-
resent statistical inferences, rather than absolute truths.
When researchers identify a region as being "active,! they mean to say that the
activation in that region during one condition (e.g., seeing a sad face) is significantly
greater than during a control condition (e.g., seeing a neutral face). What constitutes
a "significantly greater! activation is, in a way, in the eye of the beholder. Quanti-
tatively, that decision will be made through statistical analysis: activation in one
condition will be called "significantly greater! than another, if a certain threshold of
statistical certainty is crossed. Thus, lowering the threshold will create more regions
that are statistically significant, whereas raising the threshold will reduce the number
of significant regions. The choice of the threshold is largely determined by conven-
tion amongst researchers, rather than an absolute standard. Reporting a brain ac-
tivation pattern is therefore primarily a statistical interpretation of a very complex
dataset, and may be interpreted differently by different researchers.
Another factor that greatly affects the appearance of a brain activation pattern is
the choice of test and control conditions. From the preceding paragraph, it is evident
that the activation pattern is based on a comparison between a test and a control
condition. However, there may be more than one control condition and different
control conditions may produce different activation patterns. This was demonstrated
in an fMRI study by Stark and Squire (Stark & Squire, 2001). The investigators
asked subjects to respond to various visual or auditory stimuli, do a simple motor
task, or do nothing (the so-called rest condition). When rest was used as a
baseline condition, only the right parahippocampal cortex was significantly acti-
vated, and only in one cognitive task (looking at novel pictures). However, when a
simple decision task was used as the baseline, significant activation was registered
bilaterally in both the parahippocampal cortex and the hippocampal region in three
different tasks. Thus, regions that did not appear to be involved in a cognitive task
when rest was used as a baseline were significantly activated when an alternative
baseline was used. The study also illustrates that even a rest baseline condition is
associated with some degree of brain activation.

3.2. Association of brain state and psychological or behavioral measures

Correlational studies to date have related brain activation to emotional memory,

race evaluation, and personality traits. Future applications could be relevant in the
context of eyewitness testimony, trials based on recovered traumatic memories, as-
sessment of defendants in hate crime trials, or simply screening of job applicants for
undesirable personality traits. It needs to be stressed, however, that this approach
identifies an association between two variables, not a causal link between them. It is
possible that both measures are caused by another factor that has not yet been
identified.
This does not mean that the correlational approach is flawed or scientifically
invalid. It is a useful approach that allows one to search for relationships between
brain activation and potentially very many other variables. To the extent that there is
an a priori reason to search for such relations, it is entirely appropriate to report
such data. In the absence of an a priori hypothesis, it is an efficient method to de-
velop research hypotheses. Furthermore, neuroimaging is a much more powerful
tool to detect subtle relationships between two variables than traditional behavioral
methods. For example, a study of 15 subjects yielded a highly significant correlation
426 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431

between amygdala activation to happy faces and subjects! extraversion scores (see
Fig. 2; Canli et al., 2002). At the behavioral level of analysis, most studies would
require dozens, perhaps hundreds of subjects to attain similar statistical reliability.
Why the difference in effect size? One explanation is that observed behavior consti-
tutes the sum of all neural activation patterns, whereas brain imaging can focus on a
single brain structure, and may therefore pick up relationships that are too subtle to
be noticed at the behavioral level of analysis.
Correlational studies can be strengthened if they address discriminant and con-
vergent validity. Discriminant validity means that measures of two unrelated con-
cepts should also be unrelated to each other. Convergent validity means that
measures of two related concepts should also be related to each other. For example,
in the extraversion study cited above, discriminant validity was established by
showing that amygdala activation to happy faces did not significantly correlate with
constructs that were unrelated to extraversion (e.g., neuroticism or openness to ex-
perience). Convergent validity was not tested in this study. A demonstration of
convergent validity would require that amygdala activation to happy faces also
correlates with a construct related to extraversion (e.g., gregariousness).

3.3. Prediction of future behavior or pathology

The greatest concern about the ethical use of neuroimaging of emotion and
personality is in regard to its power to predict future psychopathology. The im-
portance of this concern is illustrated by proposed legislation in Britain!s Mental
Health Act (Health, 1999). This act would allow for the detention of individuals who
have not yet committed a crime, but are deemed a potential threat to public safety.
Such individuals would be diagnosed with Dangerous Severe Personality Disorder
or DSPD, a term without defined or sanctioned legal or medical status (Buchanan &
Leese, 2001). Setting aside the thorny question of whether detaining such individuals
is morally defensible, a recent analysis focused on the empirical question "to what
extent is it possible to identify those who will behave violently in the future?! (Bu-
chanan & Leese, 2001). The authors estimated that six individuals would have to be
detained for one year to prevent one violent act due to DSPD during that year.
Advocates of the proposed legislation may want to argue that neuroimaging meth-
ods could produce a more accurate prediction of future violent behavior.
The proposed Mental Health Act legislation is about the public!s right to safety
versus the individual!s right to freedom. With respect to neuroimaging methodolo-
gies, these contrasting interests translate into statistical decisions about so-called
Type I (false positive) and Type II (false negative or miss) errors. A type
I error would be committed if a person were considered potentially dangerous when,
in fact, he or she is not. A type II error would be committed if a person were con-
sidered harmless when, in fact, he or she is potentially dangerous. Because these two
errors are related, one cannot reduce the likelihood of committing one error without
increasing the likelihood of committing the other. As discussed earlier, the detection
of both structural and functional brain abnormalities is based on statistical infer-
ences. Therefore, the determination whether one individual!s brain is normal or
pathological depends on a statistical threshold that balances type I (e.g., incor-
rectly calling someone dangerous) and type II (e.g., incorrectly calling someone
harmless) errors. The tolerance for one type of error or the other depends on the cost
of being wrong, which itself is a subjective assessment.
Whereas the cost of preventive incarceration of potentially dangerous persons
who have not yet committed any crimes may seem high to some, the cost of detaining
a convicted felon beyond his sentence to protect the public may appear lower. In-
deed, this procedure is legal in some instances. On January 22, 2002, the United
States Supreme Court ruled that states can confine violent sexual offenders beyond
 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431 427

their prison term, if it can be shown that they have a mental or personality disorder
that makes it difficult for them to control dangerous behavior (Vicini, 2002). This
ruling represents a lower burden of proof, relative to the Kansas Supreme Court
Ruling, which would have required an absolute lack of control.
It is very likely that future imaging studies will be used to determine a felon!s
ability to control his behavior, because they may be more sensitive in picking up
dysfunction in impulse inhibition than a behavioral test. A particularly relevant
study investigated neural systems engaged in self-control of sexual arousal in non-
criminal male subjects (Beauregard, Levesque, & Bourgouin, 2001). Sexual arousal
in response to erotic films produced activation in limbic and paralimbic regions, but
attempted inhibition of sexual arousal was restricted to activation of the right su-
perior frontal gyrus and anterior cingulate. Both prosecutors and defense attorneys
of sexual offenders are likely to adapt these functional imaging methodologies
in the future to provide evidence for control of sexual impulses. The limitations of
the neuroimaging approach already discussed make it clear that the evaluation of
such data must be conducted with great sophistication to not be abused by either
party.
In a similar vein, a neuroimaging approach might be applied to monitor the
mental health treatment of convicted psychopaths. Psychopaths are four times as
likely to commit a violent act on release, relative to offenders diagnosed with a non-
psychopathic form of APD (Abbott, 2001; Hemphill, Hare, & Wong, 1998). Al-
though measures have been developed to identify psychopathic individuals, clinical
interventions are often unsuccessful. Indeed, persons with high PCL-R scores who
appear to respond well to behavioral therapy are more likely to re-offend than those
with lower scores who appear to respond less favorable to the intervention (Abbott,
2001; Seto & Barbaree, 1999), perhaps because they are particularly skilled in ma-
nipulating the impression made upon the therapist. Thus, some kind of objective
verification of treatment progress would be desirable. At the present time, forensic
neuroimaging cannot deliver such an evaluation, but the goal is clearly defined, al-
beit within the limitations discussed in this section.
Another ethical concern about using neuroimaging to predict future psychopa-
thology relates to issues of confidentiality. The concern is minimal for convicted
pedophiles because many states have equivalents to "Megan!s law! mandating public
access to information regarding the whereabouts of such criminals. The issue would
be thornier if brain scans could be used to identify potential pedophiles among non-
criminal persons (for reasons already discussed, this would, at best, be a statistical
prediction). Who would conduct the scan and what would precipitate such an
evaluation in the first place? If the scan suggested some likelihood of pedophilic
tendencies, how should such data be used? Would it warrant registration of this
person with law enforcement authorities? Should it be made accessible to potential
employers?
The use of prognostic scan data could be modeled after that of "notifiable! dis-
eases, particularly with respect to psychopathy, pedophilia, and related disorders
that put the public at risk. A notifiable disease is defined as one for which regular,
frequent, and timely information regarding individual cases is considered necessary
for the prevention and control of the disease (U.S. Department of Health & Human
Service, 1999). The occurrence of a notifiable disease must be relayed to the National
Notifiable Diseases Surveillance System (NNDSS), which is operated by the Center
for Disease Control (CDC) in collaboration with the Council of State and Territorial
Epidemiologists (CSTE). Amongst the 58 notifiable diseases (as of January 1, 1999)
are a number of sexually transmitted diseases (STDs) such as gonorrhea, HIV in-
fection, and syphilis. In the case of HIV infection, 33 states and 1 US territory re-
ported HIV infections by the patient!s name (as of January 1, 1999). Patients
identified with STDs are encouraged to seek counseling and treatment services. A
428 T. Canli, Z. Amin / Brain and Cognition 50 (2002) 414431

parallel treatment for persons with prognosed violent tendencies could call for
referral to treatment services and perhaps the establishment of a database accessible
to qualified parties.
Prognostic neuroimaging could not only lead to treatment referral, but could even
guide treatment strategy. For example, violent patients with amygdala damage may
require a different treatment strategy than violent patients with prefrontal damage.
This is because amygdala damage is more likely associated with instrumental vio-
lence and psychopathic tendencies whereas prefrontal damage is more likely asso-
ciated with reactive violence that is non-psychopathic (Blair, 2001). One can
speculate that some form of anger management therapy may be effective in patients
who exhibit reactive violence (i.e., may have prefrontal damage), but not in patients
who exhibit instrumental violence (i.e., may have amygdala damage).
These scenarios illustrate the wide range of potential applications for neuroi-
maging of emotion and personality. A scrupulous use of this methodology could
greatly benefit individuals and society. Naive use and uninformed interpretations of
the data, on the other hand, may compromise its benefits. For this reason it is im-
portant to be mindful of the limitations of the neuroimaging approach.

4. Concluding remarks

In light of the caveats listed above and the ethical considerations, what benefits
are to be derived from neuroimaging of emotion and personality? The likely benefits
apply to the prevention, diagnosis, and treatment of a variety of disorders and social
ills. Neuroimaging approaches could identify vulnerability factors for psychopa-
thology such as structural abnormalities, dysfunctional metabolism or activation
patterns. Preventive interventions such as medication, cognitive therapy, or lifestyle
changes could be motivated by such imaging data and progression towards psy-
chopathology could be monitored. Treatment of affective or personality disorders
could be greatly aided by neuroimaging techniques that can identify specific sub-
populations and optimize patient-treatment match. The mental status of felons to-
be-released to the public could perhaps be ascertained to provide continued mental
health treatment to those who require it, or continue incarceration of those who
show no improvement. It is the prospect of such beneficial applications that moti-
vates the continued development of neuroimaging approaches to the study of
emotion and personality.

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