European Journal of Neuroscience

European Journal of Neuroscience, Vol. 28, pp. 1222–1230, 2008 doi:10.1111/j.1460-9568.2008.06406.x

COGNITIVE NEUROSCIENCE

Empathic neural reactivity to noxious stimuli delivered to

body parts and non-corporeal objects

Marcello Costantini,1,2 Gaspare Galati,2,3,4 Gian Luca Romani1,2 and Salvatore M. Aglioti3,5
1
Laboratory of Neuropsychology, Department of Clinical Sciences and Bio-imaging, Università ‘G. d’Annunzio’, Chieti, Italy
2
ITAB Institute for Advanced Biomedical Technologies, Fondazione Università ‘Gabriele d’Annunzio’, Chieti, Italy
3
Department of Psychology, Università degli studi di Roma ‘La Sapienza’, Via dei Marsi 78, 00185 Roma, Italy
4
Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Roma, Italy
5
Centro Ricerche di Neuropsicologia, IRCCS Fondazione Santa Lucia, Roma, Italy

Keywords: empathy, functional magnetic resonance imaging, mirror systems, pain, sensorimotor contagion, social learning

Abstract
Neuroimaging studies report that the experience of observing or imagining the pain of others is mapped on a set of neural structures
that largely overlap those called into play during the personal experience of pain (the so-called pain matrix). Empathy for pain is a
multifaceted process that may be triggered by higher-order variables (such as imagination of others’ suffering) or by the direct vision
of painful situations. Most functional magnetic resonance imaging studies indicate that the empathic mapping of others’ pain may rely
on the affective and not on the sensorimotor division of the pain matrix. However, as empathy for pain is a complex, multifarious
process, it is possible that different brain regions, even beyond the classic pain matrix, may be called into action in different
circumstances. By using functional magnetic resonance imaging we explored the neural activity induced by needles deeply
penetrating a hand or a non-corporeal object. We found that observation of pain in others brought about activation in the middle
cingulate, left premotor and left and right supramarginal regions. This pattern of neural activity indicates that the direct vision of strong
painful stimuli delivered to others activates neural regions in the onlooker’s brain specifically concerned with the resonant,
interindividual sharing of basic sensorimotor reactivity to pain. We also found that bilateral posterior parietal and temporo-occipital
regions were activated during observation of painful stimuli delivered to the body of others as well as to non-body stimuli. Therefore,
our study expands current knowledge on the neural reactivity to potentially dangerous stimuli delivered in the peripersonal space.

Introduction
The experience of pain is based on sensory ⁄ discriminative and
emotional ⁄ affective components (Price et al., 1999; Craig, 2003;
Ploghaus et al., 2003) that, although correlated with each other, are
mapped in different nodes of a complex cerebral network referred to as
the pain matrix (Ingvar, 1999; Peyron et al., 2000). Indeed, although
the primary and secondary sensory cortices are mainly involved in the
sensory-discriminative aspects of pain (Bushnell et al., 1999), the
anterior cingulate and insula mainly subserve the affective-motiva-
tional components (Rainville et al., 1997).
Although pain has long been considered as an inherently private
experience, there is a clearly social dimension of pain because not only
do we perceive pain in ourselves but we can also imagine or represent
the pain of others. Only recently has this empathic dimension of pain
been investigated in a series of functional magnetic resonance imaging
(fMRI) studies in which participants imagined the pain of their
beloved (Singer et al., 2004, 2006), watched facial pain-related
behaviour (Botvinick et al., 2005) or observed static (Jackson et al.,
Correspondence: Dr S. M. Aglioti, 3Department of Psychology, as above.
E-mail: salvatoremaria.aglioti@uniroma1.it
Received 22 October 2007, revised 3 July 2008, accepted 11 July 2008
2005, 2006) or dynamic (Morrison et al., 2004) situations that were
potentially painful to stranger human models. Most of these fMRI
studies showed that only the affective components of the pain matrix
(mainly the anterior insula and anterior cingulate areas) were activated
during empathy for pain, thus suggesting that only emotional
representations of pain are shared between self and others.
Current definitions of empathy postulate that this complex psycho-
logical construct not only entails sharing the emotional state of another
person but also a number of cognitive functions such as the capacity to
take the other’s perspective (Davis, 1996; Preston & de Waal, 2002).
In this vein, it is entirely possible that the type of empathy elicited by
the conceptual understanding of the actions, feelings and emotions of
other individuals (e.g. imagining the pain of another individual) is
fundamentally different, at both the phenomenological and neural
levels, from the type of empathy triggered as a consequence of directly
observing painful stimuli delivered to the body of others. This is in
keeping with the somewhat different scenario suggested by our single-
pulse transcranial magnetic stimulation (TMS) (Avenanti et al., 2005,
2006; Minio-Paluello et al., 2006), somatosensory evoked potential
(Bufalari et al., 2007) and laser evoked potential (Valeriani et al.,
2008) studies in which we found empathy-related modulations in
cortical areas that are involved in the personal experience of pain.

ª The Authors (2008). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd

Furthermore, subsequent fMRI studies (Lamm et al., 2007b; Morig-
uchi et al., 2007; Ogino et al., 2007; Saarela et al., 2007; Benuzzi
et al., 2008; Ochsner et al., 2008) demonstrated, using a large variety
of different stimuli, that empathy for pain may recruit both affective
and sensory nodes of the pain matrix. Interestingly, indices of
reactivity to others’ pain (e.g. magnitude of BOLD signal, reduction of
motor evoked potentials, changes in amplitude of somatosensory
evoked potentials) correlated with subjective ratings of the affective or
sensory qualities of the pain attributed to the model. Importantly,
neural activity contingent upon the vicarious experience of pain is
modulated by the onlooker’s expertise. Indeed, seeing needles
penetrating different body parts brought about a higher activation of
pain-matrix-related structures in novice than in professional acupunc-
turists (Cheng et al., 2007).
Here we explored the whole neural network linked to empathy for
the pain of strangers by using fMRI in healthy subjects who observed
video-clips showing a right hand or a tomato penetrated deeply by a
needle or touched gently by a Q-tip. Our design not only allowed us to
explore the neural underpinnings of viewing strong painful stimuli
delivered to others but also to assess whether seeing painful stimuli
delivered to non-corporeal objects induced any specific changes of
reactivity in the onlooker’s brain. This may allow the genuine effect of
pain-related modulation and non-specific aversive effects to be
distinguished. Mere viewing of ‘flesh and bone’ painful stimuli
activated frontal, cingulate, parietal and temporo-occipital regions.
Additional parietal and temporo-occipital regions were activated during
observation of painful stimuli delivered to both corporeal and non-
corporeal objects. However, no regional activation specifically linked
to the observation of a needle penetrating a tomato was found, which
hinted at the specificity of the empathic mapping of others’ pain.
Materials and methods
Participants
Thirteen healthy female participants (aged 21–35 years, mean age
24.9 years, 12 right-handed) took part in the experiment. All
participants had normal or corrected-to-normal vision and were naive
as to the purposes of the experiment. Participants gave their written
informed consent to participate in the study and were paid for their
participation. The study was approved by the Ethics Committee of the
‘G. d’Annunzio’ University, Chieti, and was conducted in accordance
with the ethical standards of the 1964 Declaration of Helsinki.
Stimuli and procedure
The experimental stimuli consisted of videos showing a dorsal view of
a human right hand being either deeply penetrated by a hypodermic
Fig. 1. Selected frames from the video sequences of experimental conditions and time series of the different observation blocks.
ª The Authors (2008). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience, 28, 1222–1230
Seeing the pain of others 1223
syringe (‘needle penetrating the hand’ condition) or touched gently by
a Q-tip (‘Q-tip touching the hand’ condition). Control stimuli depicted
a static hand flanked by a static syringe or a Q-tip (‘static hand’
condition). To assess the specificity of possible effects related to
watching pain, we also used videos featuring non-corporeal stimuli,
i.e. a tomato either penetrated deeply by a syringe (‘needle penetrating
the tomato’ condition) or touched by a Q-tip (‘Q-tip touching the
tomato’ condition), and control stimuli depicting a static tomato
flanked by a static syringe or a Q-tip (‘static tomato’ condition).
Stimuli were projected onto a back-projection screen situated behind
the subject’s head and were visible through a mirror (10 · 15 cm).
Video-clips were shown in 13-s blocks with 6-s fixation periods
between blocks. Each block comprised three short video-clips
belonging to one of the six stimulus categories. To minimize
habituation effects three syringe sizes, three different colours of the
liquid of the syringe and three different Q-tips were used. In none of
the videos was the holder of the syringe or the Q-tip (or his hand)
visible. The different blocks were alternated in a fixed sequence, with
each category presented three times during each acquisition run. Each
subject underwent three consecutive acquisition runs (see Fig. 1).
Participants were instructed to watch the stimuli carefully but no
explicit request to empathize with the model’s pain was given. To try
to make attention uniform across the different conditions we informed
the subjects that, at the end of the experimental sessions, questions
would be asked about the images (colour and size of the syringe, type
of Q-tip). Moreover, we asked subjects to pay attention to the possible
sensations evoked by each category of observed stimuli.
Measures of state empathy
After fMRI acquisition we administered four measures of state
reactivity to the observed events. In particular, subjects were shown
the ‘needle penetrating the hand’ and the ‘Q-tip touching the hand’
movies and asked to evaluate on a seven-point Likert scale the
possible effect of each movie. Two measures were other-oriented and
concerned either the sensory or emotional properties of the observed
pain. To obtain these two measures of state empathy for pain,
participants were asked to report: (i) how intense was the pain
attributed by the model (sensory other-oriented pain ratings) and
(ii) how unpleasant was the pain attributed to the model (emotional
other-oriented pain unpleasantness). To obtain the two self-oriented
measures of reactivity to the status of the model, participants were
asked to rate: (iii) how intense was the effect of the movie on them
(self-oriented ratings) and (iv) how unpleasant were the stimuli to
them (self-oriented unpleasantness). A score of 0 indicated no effect
and a score of 6 indicated maximal effect. Moreover, to control for
possible non-specific response biases we also asked subjects to report
whether they had experienced any pain during observation of the
1224 M. Costantini et al.
needle in the tomato and the Q-tip on the tomato dynamic movies and
of the static hand movie where a static syringe was also present.
Measures of trait empathy
Subjects were asked to complete the Italian version (Bonino et al., 1998)
of the Interpersonal Reactivity Index (Davis, 1980, 1983, 1996), a
28-item self-report survey that consists of four subscales: (i) empathic
concern (which assesses the tendency to experience feelings of
sympathy and compassion for others in need), (ii) personal distress
(which assesses the extent to which an individual feels distress as a result
of witnessing another’s emotional distress), (iii) perspective taking
(which assesses the dispositional tendency of an individual to adopt the
perspective of another) and (iv) fantasy scale (which assesses an
individual’s propensity to become imaginatively involved with fictional
characters and situations). Current social psychological interpretations
of the different subscales posit that the first two refer to the affective
components of empathy and the last two to the cognitive components.
Magnetic resonance imaging acquisition and data analysis
All images were collected with a 1.5 T Siemens Magneton Vision
scanner with a standard head coil operating at ITAB (Fondazione
Università ‘Gabriele d’Annunzio’, Chieti, Italy). T1-weighted anatom-
ical images were collected using the Siemens multiplanar rapid
acquisition gradient-echo sequence (1 mm3 isotropic voxels, 160
sagittal slices, TR, 11.4 ms, TE, 4.4 ms). Functional images were
collected with a gradient-echo EPI sequence. Each acquisition run
included 117 consecutive volumes comprising 24 consecutive 4-mm-
thick slices oriented parallel to the anterior ⁄ posterior commissure and
covering the whole brain (TR, 3 s, TE, 60 ms, 64 · 64 image matrix,
4 · 4 mm in-plane resolution). fMRI data were analysed using SPM5
(Wellcome Department of Cognitive Neurology, Institute of Neurology,
London) according to the procedure described below. For each subject,
functional images were first corrected for head movements using a least-
squares approach and six-parameter rigid body spatial transformations
(Friston et al., 1995). The high-resolution anatomical image and the
functional images were then stereotactically normalized to the Montreal
Neurological Institute brain template used in SPM5 (Mazziotta et al.,
1995). Functional images were resampled with a voxel size of
4 · 4 · 4 mm and spatially smoothed with a three-dimensional
Gaussian filter of 6 mm full width at half maximum to accommodate
anatomical variations between subjects (Friston et al., 1995). Images
were subsequently analysed using a random effect approach. The time
series of functional magnetic resonance images obtained from each
participant were analysed separately. The effects of the experimental
paradigm were estimated on a voxel-by-voxel basis using the principles
of the general linear model extended to allow the analysis of fMRI data
as a time series (Worsley & Friston, 1995). Each experimental block
was modelled using a boxcar, convolved with a canonical haemo-
dynamic response function chosen to represent the relationship between
neuronal activation and blood flow changes. These single-subject
models were used to compute four contrast images per subject, each
representing the estimated amplitude of the haemodynamic response in
one of the four movie conditions (needle penetrating the hand, Q-tip
touching the hand, needle penetrating the tomato and Q-tip touching the
tomato) relative to the respective static image.
Contrast images from all subjects were entered into an anova with
non-sphericity correction, as implemented in SPM5 (Worsley & Friston,
1995), in order to identify regions where the effect of any of these
contrasts was significant, i.e. regions discriminating any of the four
ª The Authors (2008). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd
movies from the respective static image, at a statistical threshold of
P < 0.01 corrected for multiple comparisons over the total amount of
analysed brain volume using false discovery rate (Genovese et al., 2002).
Then, for each identified region, we computed the BOLD percentage
signal change in each movie condition (relative to the respective static
condition) for each subject, by re-estimating the individual general linear
model on the average fMRI time course across all voxels in the region.
These average regional response estimates were entered into region-
specific group repeated-measures anova with object (‘hand’ vs.
‘tomato’) and stimulus (‘syringe’ vs. ‘Q-tip’) as main factors.
Correlational analyses
We computed correlations between differential neural activity and
measures of state and trait empathy. Therefore, we used the regional
BOLD percentage signal changes (computed as described above)
during observation of the needle penetrating the hand, with respect to
the static hand condition. Pearson correlation coefficients were
computed between these regional responses and the different other-
referred ratings of the pain qualities derived from observation of the
needle in hand movie and self-referred measures of reactivity to the
pain of others. Correlations with trait empathy scores were also
performed. In order to control for the number of possible comparisons,
correlational analyses were performed only for the brain regions where
neural activity was higher for body than non-body objects or for
needle in hand than for the other three observation conditions (Q-tip
on hand, needle in tomato and Q-tip on tomato).
Results
From the group-level whole-brain analysis of functional magnetic
resonance images, we identified eight different cortical regions where
the BOLD signal was significantly different during observation of any
of the four movie conditions compared with the respective static
image. The eight regions were located in the left precentral gyrus and
right middle cingulate cortex, and bilaterally in the supramarginal
gyrus, intraparietal sulcus and occipito-temporal cortex (see Table 1
and Fig. 2).
Left precentral gyrus
The cluster was centred on the precentral gyrus with about 57% of the
voxels within this region, roughly corresponding to Brodmann area 6.
Additional voxels fell within the pars opercularis of the inferior frontal
gyrus, corresponding to Brodmann area 44 (34%). The repeated-
measures anova on the percentage BOLD signal change in this cluster
highlighted the significance of the Object factor (F1,48 = 15.1;
P < 0.001), with higher activation during observation of hand-related
(BOLD signal change, 1.08) than tomato-related (BOLD signal change,
0.50) movies. The Stimulus factor was also significant (F1,48 = 19.9;
P < 0.001), with higher activation during observation of pain-related
(BOLD signal change, 1.08) than touch-related (BOLD signal change,
0.50) movies. The interaction was significant (F1,48 = 4.2; P < 0.05)
because the effect of watching a needle vs. a Q-tip was higher for hand.
Moreover, neural activity was maximal and significantly higher for
needle in hand than for any other observational condition (see Fig. 2).
Middle cingulate cortex
This cluster was centred on the middle cingulate cortex, roughly
corresponding to Brodmann area 32, and partially extended to the
European Journal of Neuroscience, 28, 1222–1230
 Seeing the pain of others 1225

Table 1. Montreal Neurological Institute (MNI) coordinates of peaks of respectively). The Stimulus factor turned out to be significant
relative activation in the eight cortical regions where BOLD signal was (F1,48 = 22.2; P < 0.001), with higher activation during observation
significantly different during observation of any of the four movie conditions of pain-related (BOLD signal change, 1.07) than touch-related (BOLD
compared with the respective static image signal change, 0.52) movies. The interaction was significant
(F1,48 = 4.5; P = 0.039) because the effect of watching a needle vs.
Main local
maxima (MNI a Q-tip was higher for hand than for tomato movies. Moreover, neural
Regions of activation coordinates) activity was maximal and significantly higher for observation of
needle in hand than for all the other conditions.
Anatomical Extent of
location the cluster Subdivisions Relative
of local maxima (mm3) BA extent (%) x y z
Left intraparietal sulcus
Left precentral 3.750 6 57 )52 4 32 The cluster was centred on the intraparietal sulcus, with about 63% of
44 34 )36 4 32 the voxels within Brodmann area 7. Additional voxels were located
Right MCC 335.0 32 100 12 28 32
within Brodmann area 40 (29%). Only the Stimulus factor turned out
Left SMG 4.607 2 41 )52 )32 36
48 20 )56 )24 36 to be significant (F1,48 = 19.4; P < 0.001), with higher activation
40 16 )52 )36 40 during observation of pain-related (BOLD signal change, 1.63) than
3 12 )56 )24 44 touch-related (BOLD signal change, 0.88) movies.
Right SMG 1.354 3 40 56 )24 40
2 27 56 )28 40
48 22 60 )24 36
Left IPS 6.069 7 63 )28 )52 48 Right intraparietal sulcus
40 29 )40 )44 48 The cluster was centred on the intraparietal sulcus, with about 87% of
Right IPS 2.752 7 87 28 )64 64
Left middle 22.236 37 47 )44 )68 4 the voxels within Brodmann area 7. The anova on this cluster showed
occipital gyrus 19 38 )44 )68 )12 the significance of the Stimulus factor (F1,48 = 14.2; P < 0.001), with
18 12 )32 )92 )4 higher activation during observation of pain-related (BOLD signal
Right middle 26.286 37 44 44 )64 8 change, 1.49) than touch-related (BOLD signal change, 0.84) movies.
temporal gyrus 19 36 48 )80 4
18 13 32 )92 0
Left temporo-occipital cluster
BA, Brodmann area; MCC, middle cingulated cortex; SMG, supramarginal
gyrus; IPS, intraparietal sulcus. The cluster was centred on the middle occipital gyrus with about 47%
of the voxels within Brodmann area 37. The other voxels encom-
superior frontal gyrus. The analysis of the BOLD signal change passed Brodmann areas 19 and 18 (38% and 12%, respectively). The
showed that the Object factor was significant (F1,48 = 27.1; anova on this cluster showed the significance of the Stimulus factor
P < 0.001), with higher activation during observation of hand-related (F1,48 = 64.5; P < 0.001), with higher activation during observation
(BOLD signal change, 0.31) than tomato-related (BOLD signal of pain-related (BOLD signal change, 1.94) than touch-related (BOLD
change, )0.22) movies. The Stimulus factor was also significant signal change, 1.04) movies.
(F1,48 = 10.0; P < 0.001), with higher activation during observation
of pain-related (BOLD signal change, 0.17) than touch-related (BOLD
signal change, )0.08) movies. The interaction was highly significant Right temporo-occipital cluster
(F1,48 = 13.3; P < 0.001) because the effect of watching a needle vs. a The cluster was centred on the middle temporal gyrus with about 44%
Q-tip was higher for hand than for tomato movies. Importantly, neural of the voxels within Brodman area 37. The other voxels encompassed
activity was maximal and significantly higher for the needle in hand Brodmann areas 19 and 18 (36% and 13%, respectively). Again, only
than for any other observation condition. the Stimulus factor turned out to be significant (F1,48 = 64.5;
P < 0.001), with higher activation during observation of pain-related
(BOLD signal change, 1.66) than touch-related (BOLD signal change,
Left supramarginal gyrus 0.80) movies.
The cluster was centred on the supramarginal gyrus. It encompassed In no brain region did we find higher activations for touch than pain
four different Brodmann areas, i.e. 2, 48, 40 and 3 (41%, 20%, 16% observation.
and 12%, respectively). The Object factor was significant (F1,48 = 7.3;
P < 0.001), with higher activation during observation of hand-related
(BOLD signal change, 1.26) than tomato-related (BOLD signal Measures of state empathy for pain and trait interpersonal
change, 0.90) movies. Moreover, the Stimulus factor was significant reactivity index
(F1,48 = 28.1; P < 0.001) because activation was higher during One-sample t-tests showed that Likert ratings related to observation of
observation of pain-related (BOLD signal change, 1.38) than touch- the movies of the needle penetrating the hand were significantly
related (BOLD signal change, 0.79) movies. Although the interaction different from 0 (no effect) for self-oriented pain intensity [mean (SD):
was not significant, neural activity was significantly higher for needle 3.1 (2.1)] and unpleasantness [4.2 (1.7)], as well as for intensity [4.2
in hand than for any other observation condition. (1.9)] and unpleasantness [5.0 (2.2)] of other-oriented reactivity
(P < 0.001 in all cases). Ratings of self-referred pain intensity were
lower than self-referred unpleasantness (P = 0.03). Ratings of self- or
Right supramarginal gyrus other-referred pain intensity and unpleasantness related to observation
The cluster was centred on the supramarginal gyrus. It encompassed of the remaining movies were not significantly different from 0 [Q-tip
three Brodmann areas, i.e. 3, 2 and 48 (40%, 27% and 22%, touching the hand: intensity 0 (0), unpleasantness 0.75 (1.3); needle

ª The Authors (2008). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience, 28, 1222–1230
1226 M. Costantini et al.

Fig. 2. Regions of relatively higher activation (and percentage signal change) during observation of any of the four dynamic observation conditions (needle
penetrating the hand, Q-tip touching the hand, needle penetrating a tomato and Q-tip touching a tomato) vs. observation of the respective static baseline stimulus.
Group activation data are rendered on the cortical surface of a ‘canonical’ brain (Mazziotta et al., 1995). IPS, intraparietal sulcus; MCC, middle cingulated cortex;
SMG, supramarginal gyrus.

penetrating the tomato: intensity 0.5 (1.2), unpleasantness 1.1 (1.5);
static hand (and static syringe): intensity 0.75 (1.4); unpleasantness
0.75 (1.4)]. This result rules out the possibility that the ratings during
observation of the movies of the needle in hand were due to a non-
specific response bias. Scores on the four subscales of the Italian
version of the Interpersonal Reactivity Index trait empathy test were as
follows: emphatic concern: 10.4 (4.7); fantasy scale: 12.6 (7.3);
personal distress: 7.2 (4.4); perspective taking: 14.6 (3.9). These
values are largely in accord with previous reports in samples of similar
size (Singer et al., 2004; Lamm et al., 2007a).
Correlation between brain activity contingent upon
observation of pain in others and measures of empathy
Discovering the possible relation between measures of state (either
sensory or emotional) or trait empathy and neural activity contingent
upon the observation of needles penetrating a hand vs. the observation
of a static hand is crucial for understanding the nature of the empathic
phenomena called into play in our experimental conditions. With the
aim of clarifying this issue, we carried out correlation analyses
between percentage signal changes in the clusters of state empathy for
pain scores and trait interpersonal reactivity scores. Based on the
a-priori criterion defined above (see Materials and methods), corre-
lational analyses were performed only on the clusters for which neural
activity was specifically associated with body or body pain (signif-
icance of the main effect of Object or of the Object · Stimulus
interaction). Therefore, the analysis involved only the left precentral,
middle cingulate, left and right supramarginal clusters.
We found that the activation of the middle cingulum was positively
correlated with the unpleasantness of the pain attributed to the model
(r = 0.60, P = 0.04) and to the self (r = 0.63, P = 0.028), and with the
fantasy scale (r = 0.71, P = 0.009) (Fig. 3, bottom part). The

ª The Authors (2008). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience, 28, 1222–1230
 Seeing the pain of others 1227

Fig. 3. Correlation between percentage BOLD signal change observed within the clusters activated during observation of a needle penetrating the hand vs. static
hand and individual differences in pain rating and trait empathy as measured by Interpersonal Reactivity Index. The lines represent the linear best fit; r refers to the
coefficient of correlation. All correlations are significant at the P < 0.05 level. MCC, middle cingulated cortex; SMG, supramarginal gyrus.

Table 2. Correlation between the percentage BOLD signal change in the four clusters where activation was specifically related to observation of movies of needle
in hand and subjective scores concerning trait ⁄ state empathy

Precentral_LH MCC Left SMG Right SMG

Cortical regions r-value P-value r-value P-value r-value P-value r-value P-value

Measures of trait empathy

Empathic concern 0.29 0.36 0.51 0.09 )0.31 0.32 )0.12 0.70
Fantasy scale 0.26 0.43 0.71* 0.009* )0.18 0.57 )0.19 0.55
Personal distress 0.23 0.47 0.41 0.19 )0.56 0.06 )0.32 0.31
Perspective taking 0.46 0.13 )0.17 0.59 )0.73* 0.008* )0.60* 0.038*
Measures of state empathy, self-oriented
Unpleasantness )0.16 0.62 0.63* 0.028* 0.28 0.38 )0.35 0.26
Sensory pain rating )0.32 0.31 0.00 1 0.07 0.82 )0.48 0.12
Measures of state empathy, other-oriented
Pain unpleasantness rating 0.05 0.87 0.60* 0.04* 0.07 0.84 )0.17 0.59
Pain intensity rating 0.07 0.83 0.36 0.25 0.27 0.39 )0.15 0.65

*Significant r-values and P-values. LH, left hemisphere; MCC, middle cingulated cortex; and SMG, supramarginal gyrus.

activation of the supramarginal gyrus was instead negatively corre-
lated, in both hemispheres, with the perspective taking subscale of the
Interpersonal Reactivity Index (left hemisphere: r = )0.73; P = 0.008;
right hemisphere: r = )0.60; P = 0.038) (Fig. 3, top).
To highlight the specificity of the significant correlations, Table 2
reports all of the correlations performed on the four clusters.
Discussion
In the present fMRI study healthy subjects observed needles deeply
penetrating the hand of a stranger model that induced a strong
involvement of the observer in the painful scenario. The absence of
any emotional or social bond between onlooker and model and the
direct vision of potentially very painful stimuli may have evoked a
type of ‘simulative’ empathic pain linked more to the sense of the
physiological condition of one’s own material body (Craig, 2002,
2003) than to emotional resonance with others’ pain or abstract
comprehension of it. This might have induced a specific sensorimotor
mapping of others’ pain. A clear increase of neural activity contingent
upon pain observation was found in frontal and parietal structures
linked to first-hand pain experience.
An increase of neural activity in the middle cingulate cortex was
also found. Although the cingulate cortex is part of the affective node
of the pain matrix, the specificity of the activation found in our study

ª The Authors (2008). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience, 28, 1222–1230
1228 M. Costantini et al.
may be more related to behavioural reactions to pain than to the
analysis of its affective qualities. Moreover, the present study explored
the neural systems recruited during the observation of needles
penetrating a non-corporeal object that, in principle, should not lead
to any pain embodiment.
Comparisons of the BOLD signal with respect to the baseline in
conditions where painful or non-noxious stimuli were delivered to
body parts or non-corporeal objects brought about significant changes
of neural activity in left precentral, right cingulate, bilateral parietal
and temporo-occipital areas. A specific increase of neural activity
contingent upon observation of needles penetrating a hand was found
in the right cingulate, left and right supramarginal gyrus, and left
precentral regions. Interestingly, these areas are probably involved in
mapping affective and sensory qualities as well as behavioural
reactions to the personal experience of pain (Ingvar, 1999; Peyron
et al., 2000; Rainville, 2002; Farrell et al., 2006). Neural activity in an
additional set of areas, i.e. left and right intraparietal sulcus and left
and right temporo-occipital regions, was higher during observation of
needles, no matter whether they penetrated a hand or a tomato.
Therefore, the suggestion is made that these regions are not
specifically linked to a vicarious processing of others’ pain but rather
to the representation of potentially dangerous and aversive stimuli.
Pain of a model in the brain of an onlooker
Classically, definitions of empathy in psychological research have
emphasized the emotional aspects of the inter-individual sharing of
experiences (Mehrabian & Epstein, 1972). More recent accounts of
empathy in social psychology (Davis, 1996) and cognitive neurosci-
ence (de Vignemont & Singer, 2006) research have underscored its
complexity and multidimensionality. Indeed, empathy comprises not
only emotional but also cognitive and interoceptive components that
allow a profound experiential understanding of others’ mental states.
This is also true in the case of empathy for pain. Seeing someone get
hurt may not produce only compassion; indeed, it may also make us
shiver, wince, cringe or even feel a twinge similar to what we believe
the model is feeling. The notion that empathy for pain may imply the
simulation of sensory as well as emotional qualities of others’ pain
may seem at odds with the first fMRI studies converging to indicate
that only the affective component of the pain matrix is involved in
empathy for pain and that only emotional representations of pain are
shared between self and others (Morrison et al., 2004; Singer et al.,
2004, 2006; Botvinick et al., 2005; Jackson et al., 2005, 2006).
Indeed, this affective recruitment seemed to occur despite several
differences in the experimental paradigms, ranging from top–down
(presence or absence of affective bonds between observer and model)
to bottom–up variables (imagined pain, vision of impending painful
stimuli or of facial expressions of pain). Our previous TMS (Avenanti
et al., 2005, 2006; Minio-Paluello et al., 2006), somatosensory evoked
potentials (Bufalari et al., 2007) and laser-evoked potentials (Valeriani
et al., 2008) studies, however, highlighted the possible sensorimotor
side of empathy for pain and suggested that observers and victims of
pain may exhibit the same physical reactions. More importantly,
subsequent fMRI studies showed changes of the BOLD signal in both
the affective and sensorimotor pain matrix during the observation of
pain exacerbation in the faces of patients with chronic pain (Saarela
et al., 2007). One may note that studies tend to attribute any area
activated during the vicarious experience of others’ pain to the pain
matrix. However, it has been recently suggested that the experience of
pain does not derive only from activation of the pain matrix but also
from its interaction with a large variety of brain regions (Tracey &
Mantyh, 2007). This is particularly true in chronic pain where even
ª The Authors (2008). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd
activity in the default-mode network is disrupted (Baliki et al., 2008).
In this broader perspective, the four regions that in this study seemed
linked to the vicarious experience of others’ pain, i.e. right cingulate,
left precentral areas and left and right supramarginal gyri, contribute
more or less directly to the first-hand experience of pain. The cingulate
cortex is one of the key activity areas in pain processing (Apkarian
et al., 2005; Tracey & Mantyh, 2007). Studies indicate that the
premotor cortex is also activated when painful stimuli are delivered to
the upper limb (Farrell et al., 2005). Finally, the parietal cortex is
activated during pain perception stimulation (Duncan & Albanese,
2003; Porro et al., 2003) as well as during pain anticipation (Porro
et al., 2002; Berns et al., 2006). Therefore, our data suggest that
specific aspects of the inter-subjective representation of others’ pain
may be inherently linked to activity in areas that are related to personal
experience of pain. Moreover, the results suggest that empathy for
pain induced by the direct vision of ‘flesh and bone’ stimuli triggers
the automatic mapping of the noxious stimulus onto the observer’s
body in both sensorimotor and affective pain-processing areas.
Influence of state empathy and trait personality scores on
mirroring others’ pain
A complex pattern of positive and negative correlations between
neural activation in the areas specifically activated during observation
of pain in another individual and subjective measures of state and trait
empathy was found. The increase of neural activity in the middle
cingulate cortex was positively correlated with the unpleasantness of
the pain attributed to the model and with self-oriented unpleasantness.
The cingulate area is activated during the real experience of cutaneous
and muscle pain (Vogt, 2005). Relevant to the present result is that,
whereas the anterior cingulum is more concerned with emotional and
visceral integration of pain, the middle cingulum is more involved in
response selection, fear avoidance and skeletomotor reactions to the
pain stimulus (Vogt, 2005). In view of this, the suggestion is made that
the cingulate activity induced by the direct vision of ‘flesh and bone’
stimuli delivered to others is linked to the simulated implementation of
emotional and physical reactions to the observed pain. This is in
keeping with a recent study indicating that the middle cingulate cortex
has a role in linking pain observation with motor processing (Morrison
et al., 2007). Neural activity in the cingulate cortex also positively
correlated with the Interpersonal Reactivity Index fantasy scale, which
assesses an individual’s propensity to become imaginatively involved
with fictional characters. Although social psychology and cognitive
neuroscience still lack a common lexicon, it is held that the fantasy
scale is an index of cognitive empathy. Studies indicate that
individuals with high cognitive empathy exhibit high levels of
automatic mimicry of postures, mannerism and facial expression
during interpersonal communications (Chartrand & Bargh, 1999). Our
result may extend this notion by showing that the ability to
imaginatively transpose into the feelings and inner states of others
may modulate the reactivity to the direct viewing of others’ pain.
Interestingly, a specific link between reactivity to others’ pain and
cognitive empathy has been also found in a recent TMS study on the
lack of empathy for pain in individuals with Asperger syndrome
(Minio-Paluello et al., 2008).
The other set of correlations found in the present study involves
neural activity in the left and right supramarginal cortex in the parietal
lobe that turned out to be negatively correlated with the perspective
taking subscale of the interpersonal reactivity index. Interestingly,
parietal regions are not only involved in pain processing (Dong et al.,
1994, Dong et al., 1996; Hsieh et al., 1995; Svensson et al., 1997;
Casey et al., 1994, 1996; Oshiro et al., 2007) but also in a number of
European Journal of Neuroscience, 28, 1222–1230

cognitive tasks where different emotional and conceptual perspectives
have to be taken (Ruby & Decety, 2003, 2004; Lamm et al., 2007a). The
negative correlation reported above indicates that individuals who are
less inclined to take the perspective of others present higher activity in
the left and right parietal areas. This seemingly counterintuitive result
may be explained by the need to reduce the drawback of assuming the
painful perspective of others and taking the burden of others’ pain. In
this view, our result may indicate that individuals with a high tendency
to take the perspective of others attempt to control the risk of actually
feeling pain (sensorimotor and emotional contagion) by reducing neural
activity in sensorimotor structures involved in pain processing.
All in all, the complex pattern of correlations found in the present
study supports the view that empathy for pain is not a unitary
phenomenon and that sensory and affective representations of others’
pain may be shared in both sensorimotor and affective nodes of the pain
matrix. This in keeping with recent fMRI studies (Gu & Han, 2007;
Lamm et al., 2007a; Moriguchi et al., 2007; Benuzzi et al., 2008). In
the study of Saarela et al. (2007), for example, emotional empathy
scores correlated with increased neural activity in the left anterior
insula ⁄ inferior frontal region. Moreover, in the above study, the
intensity of the pain attributed to the model correlated with increased
activity in the anterior cingulate, inferior parietal cortex and anterior
insula bilaterally, thus hinting at a complex interplay between a number
of brain regions that contribute to the experience of pain even beyond
the traditional concept of the pain matrix (Tracey & Mantyh, 2007).
Moreover, our study suggests that the observational derivation of
qualities of others’ pain is influenced by both state and trait measures of
interpersonal reactivity. Importantly, deriving this information through
observation may allow the social learning of reactions to pain.
Neural correlates of visual processing of aversive stimuli
In addition to the four regions specifically linked to processing the
pain of a human model, we found four additional posterior parietal and
temporo-occipital regions activated during observation of painful
stimuli delivered to both human and non-human objects. These
activations can hardly be attributed specifically to empathic reactivity
to others but may code a number of additional properties (e.g.
attentional salience, fear and aversiveness) of the observed stimuli.
Distinct activation patterns induced by observation and imagination of
painful and fear stimuli were recently reported in an fMRI study
(Ogino et al., 2007). This study reported that, whereas the anterior
cingulate cortex, right anterior insula, cerebellum, posterior parietal
cortex and secondary somatosensory cortex region were active during
pain imagination, the anterior cingulate cortex and amygdala are
associated with the viewing of images evoking fear (Ogino et al.,
2007). Although our subjects were screened for the presence of needle
phobia and none of the participants spontaneously reported fear during
needle observation, no specific question concerning the fear evoked by
the stimuli was asked. Therefore, no clear inference can be drawn here
and only future studies can clarify this issue.
It is worth noting, however, that cortical regions largely overlapping
with those activated by needle in hand and tomato in the present study
are involved in the visual processing of aversive visual stimuli
delivered in the peripersonal space (Lloyd et al., 2006). Moreover,
observation of pictures showing potential threats to another individual
brought about activation of a set of visuo-spatial areas including
temporal-occipital and parietal areas (Lloyd & Morrison, 2008).
Therefore, the suggestion is made that these regions may be related to
the detection of potentially dangerous and aversive stimuli in the
peripersonal space.
ª The Authors (2008). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience, 28, 1222–1230
Seeing the pain of others 1229
Conclusion
Our study underscores the complexity of empathy and its neural
basis by suggesting that cortical areas in addition to those of the
classic pain matrix may contribute to empathic mapping of others’
pain. Moreover, different types of empathy for pain are mapped in
different neural structures. Symbolic forms of empathy for pain,
such as imagining others’ pain, may be mapped in affective nodes
of the pain matrix. For example, it may be noted that, unlike many
fMRI studies of empathy for pain based on more emotional stimuli
(e.g. Singer et al., 2004, 2006; Saarela et al., 2007), we did not find
any insular activation, a region probably mapping emotional
qualities of others’ pain. In this vein, observation of stimuli that
are adept at eliciting a strong ‘flesh and bone’ involvement in the
painful scenario brings about their mapping in regions coding
sensorimotor reactions to them. Thus, the social dimension of pain
in humans may extend from emotional to very basic sensorimotor
levels of neural processing. The basic level of empathy tested in our
study may occur prior to the establishment of any social or affective
bond with other individuals and may be important for the social
learning of sensorimotor reactions to pain. Finally, as an additional
point of novelty, we highlight that bilateral parietal and temporo-
occipital areas react to aversive stimuli delivered to body and non-
body objects.
Acknowledgements
We are grateful to Dr Antonio Ferretti, Dr Massimo Caulo and Prof. Armando
Tartaro for their help in collecting data. This research was supported by grants
from Ministero Italiano dell’Università e della Ricerca, Fondo Italiano Ricerca
di Base, Italy.
Abbreviations
fMRI, functional magnetic resonance imaging; TMS, transcranial magnetic
stimulation.
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