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The Vicarious Brain
Christian Keysers Valeria Gazzola
Netherlands Institute for Neurosciences and University of Groningen
Whether one looks at traditional hunter gatherers or modern scientists, social skills
becomes key to success. In the modern world, the capacity to learn from others, to sense
where the Zeitgeist is going, to motivate and lead a team and to convince others at
conferences and through papers are often the determining factors of professional scientific
success. Good hunter-gatherers need to learn from the elders how to hunt and where to find
food. They need to work with a romantic partner to provide food and safety to their children.
The ability to charm and seem trustworthy is key to reproductive success. During
hominization, our brain was therefore under great pressure to develop mechanisms that
enable humans to connect with the minds of other humans, to learn from, interact and
communicate with them.
In this chapter, we will explore one specific family of neuronal mechanisms that seem
deeply engrained in the architecture of our brain and that make us intuitively able to connect
with the minds of other individuals. We will speak of a family of mechanisms because
similar mechanisms seem to exist in at least three domains of human experience: actions,
sensations and emotions. In the first section, we will review evidence that viewing the actions
of others triggers neural representations of ones own actions as if performing similar actions.
We will call these visual activations ‘vicarious motor activations’, where vicarious reflects
the fact our actions are triggered as if we were in the stead of the person we observe. In the
second section, we will show that viewing others in situations that would make us feel
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somatosensory sensations vicariously activates brain regions normally involved in feeling our
own, corresponding somatosensory sensations. In the third section, we will show how certain
regions involved in feeling emotions get vicariously activated while viewing the emotions of
others. We will briefly discuss evidence for the evolutionary continuity of these emotional
systems by looking at evidence for empathy in rodents. We will then tie these sections
together, to show how combining vicarious motor, somatosensory and emotional activations
allows one to empathically get under other people’s skin, and feel as they would, sharing
their bodily experiences. We will show, that this system does not allow us to truly feel what
others feels, but rather projects our own states onto others. We will propose that Hebbian
learning could explain how the brain develops the capacity to vicariously activate its own
states while witnessing those of others. We will conclude by suggesting that this system
could interact with regions involved in theory of mind, and show that information transfer
between individuals can be directly measured.
Vicarious Motor Activations
Mirror Neurons in Macaque Monkeys
The first evidence for vicarious activations in the primate brain stems from the discovery of
mirror neurons in monkeys[1]. These neurons, originally found in the premotor region F5 of
the macaque brain respond both when the monkey performs a goal directed action (e.g.
grasping) and when observing another individual perform a similar action[2]. Each neuron in
F5 has a restricted set of actions that it seems to be programming, with a particular neuron
responding when the monkey grasps an object with the hand, and another that may respond
when the monkey grasps with the hand or the mouth. The set of effective motor actions
determines a motor tuning curve. Electro-stimulation of area F5 in monkeys triggers the
execution of complex motor behaviors, e.g. grasping and taking to the mouth, evidencing that
this region is indeed involved in motor control of complex actions[3]. Interestingly, about
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10% of the neurons in F5 also respond when the monkey sees or hears similar actions be
performed by others[1, 4-7]. The set of observed actions that triggers activity in an F5 neuron
can be called its sensory tuning curve. In mirror neurons, the sensory and motor tuning curve
must overlap, that means, that there is at least one action that is associated with a discharge in
the mirror neuron both when the monkey performs the action (without being able to see or
hear itself do so) and when the monkey sees someone else perform a similar action. For many
of these neurons, the sound of the same action will also trigger a significant response,
showing that some mirror neurons can represent an action independently of whether it is
performed, heard or seen[5, 6]. How tightly the sensory and motor tuning curve correspond
differs from mirror neuron to mirror neuron. A minority of mirror neurons (about 30%),
seems to have very similar tuning curve during execution and observation, and are called
‘strictly congruent’[1, 7]. For the majority of mirror neurons, however, the correspondence is
less tight, and they are called ‘broadly congruent’[1, 7]. Typically, such neurons respond to
the observation of more actions than they seem to trigger execution for. A broadly congruent
mirror neuron might for instance respond only during the execution of a precision grasp of a
small object with the hand, but not to the execution of grasping with the mouth. During
observation, however, it might respond to both a precision grasp with the hand, and the sight
of grasping with the mouth. Strikingly, the effective observed actions in broadly congruent
mirror neurons are often actions that have the same goal as the effective executed action (e.g.
grasping, i.e. getting the object).
The combination of broadly and strictly congruent mirror neurons ensures that the
premotor cortex of an observing monkey has information about both the goal and the means
of other people’s actions: the goal, through both the activity of broadly and strictly congruent
mirror neurons, and the specific means through the activity of strictly congruent mirror
neurons[8]. Direct evidence for the fact that mirror neurons code information about what
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action another individual is performing comes from a study in which we used simple
classifiers to show that the firing pattern of a mirror neuron can discriminate which of two
actions was performed with over 90% accuracy, independently of whether the action was
performed by the monkey itself, or by someone else (heard or seen)[5].
Later studies have shown that neurons in the inferior parietal lobe (region PFG and
IPS, Figure 1 left) have similar properties[4, 7, 9]. In addition, neurons in the dorsal premotor
cortex of the monkey seem to respond both when the monkey uses a joystick to move a
cursor to a target position and when another monkey do so, by simply witnessing the
movement of the cursor[10]. Also, some neurons in parietal region LIP respond both when a
monkey moves its own eyes (and electro-stimulation of that region can trigger eye
movements), and when the monkey sees another monkey perform similar eye
movements[11]. Most of the brain, however, has not yet been explored for the presence of
mirror neurons, and it is therefore possible that mirror neurons for hand actions or other
motor programs might exist elsewhere in the monkey’s brain[12]. Mirror neurons also exist
in song-birds, in which neurons of the telecephalic nucleus HVC respond both when the bird
itself sings and when it hears other birds sing[13] and similar neurons also exist in the bird’s
auditory association region, Field L[14].
Detecting Vicarious Activations in Humans
A number of techniques have been used to examine if humans have brain activity that
suggests the presence of mirror neurons. The most prominent amongst these techniques are
fMRI, EEG and TMS. A smaller number of studies have also used neurological lesions and
single cell recordings in intractable epileptic patients.
Traditional FMRI. the most prominent techniques in the study of a potential human
mirror neuron system (MNS) is probably fMRI (and initially PET), which allows to measure
brain activity when participants perform actions and while they witness others perform
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similar actions. In a recent study, for instance, we used fMRI to scan 16 participants while
viewing others perform an action and while performing similar actions. To avoid blurring,
and potentially creating spurious overlaps between regions involved in action execution and
observation we analysed the data without the usual smoothing and group analyses[16].
Results indicated a broad network of voxels in which participants showed vicarious motor
activations, that is, voxels activated while they perform an action and while viewing the
actions of others. This network included the ventral premotor cortex (vPM) and anterior
inferior parietal lobule (region PFG), regions thought to correspond to areas F5 and PFG in
the monkey, where mirror neurons had been recorded from. However, it also included a
number of additional regions. The primary somatosensory cortex, in particular its most
posterior cytoarchitectonic region called BA2 (for Brodmann Area 2), was the region where
most participants showed vicarious activations. We will come back to this finding in the next
section. Also the dorsal premotor (dPM), in which mirror like neurons had been recorded
from in monkey[10] turned out to show a very significant number of voxels with vicarious
activations. Additionally, the supplementary motor area (SMA) was found to have that
property, and the cerebellum (See Figure 1 right). This lead us to suggest that mirror neurons
might exist in more regions than previously expected[12]. Of course, the fact that a voxel is
activated by both action observation and action execution is compatible with but no guarantee
for the presence of mirror neurons in its midst[16]. With each voxel containing over a million
neurons, it could contain some that only respond during execution and others that only
respond during observation, with none responding to both[16]. Also, fMRI has been shown to
be sensitive to synaptic activity even in the absence of robust changes in firing rate[17]. This
means that activity of a voxel in two conditions could be due to modulatory input that is
unable to trigger neural firing by itself but suffices to increase BOLD activity, in one or both
the conditions. Other methods, reviewed below, help us disentangle some of these
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alternatives. Our suggestion, that vicarious motor activations extend beyond the vPM and
PFG was initially met with skepticism. However, two recent meta-analysis of many fMRI
papers in which the actions of others were observed came to a similar conclusion[15, 18].
Pattern classification fMRI. Pattern Classification fMRI uses traditional fMRI data
but analyzes the data from the perspective that the nervous system represents information in
population codes, over millions of neurons spread over multiple fMRI voxels[19]. Embracing
this vision, we asked if there is evidence that the pattern of differences in activity that
distinguishes two actions during execution is the same as that distinguishing these two
actions during perception. We used data from our original action execution and action
listening experiment [20], but now trained a pattern classifier to use activity patterns over all
voxels in three brain regions (premotor, somatosensory and inferior parietal brain regions) to
discriminate whether participants in the scanner heard hand or mouth actions. In all three
regions, the pattern classifier learned to distinguish these two types of action sounds. We then
stopped training, and queried the pattern classifier with trials in which the participants
executed these two types of actions in the scanner. The results showed that the pattern
classifier could correctly discriminate action execution trials using rules learned during action
perception above chance (p<0.05) in all three regions. Shortly after our experiment,
Oosterhof et al. [21] showed that a similar cross-modal classification can be done using
movies of different types of actions in the parietal cortex. These findings are important in two
ways. First, they show that listening to or observing the actions of others not only activates
premotor, somatosensory and posterior-parietal regions, but that the spatial pattern of this
activity also caries information about what action someone else is performing, suggesting that
vicarious motor activations could contribute to the perception of other people’s actions.
Second, by showing that a classifier trained on motor execution trials can distinguish action
perception trials shows that the information is stored in a spatial code that is common to
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action perception and execution. This common coding is reminiscent both of the behavior of
individual mirror neurons in the monkey brain[5] and of the influential common coding
theory of Prinz and collaborators [22].
Information flow across brains. One of the core prediction of mirror neurons in
monkeys, is that they would allow the brain of an observer to resonate with the brain activity
of an observed individual, i.e. that brain activity would go up and down in the observers in
ways that mirror the temporal sequence of the observed actions. Recently, by scanning brain
activity of both a person making gestures and the person viewing these gestures, we could
visualize how the somatosensory and premotor regions of the observer indeed start to
resonate over time with those of the gesturer[23]. By comparing brain activity in a story-teller
with that in a story listener, similar findings could be observed for verbal communication[24].
This findings have lead to the emergence of a new approach to neuroimaging that analyses
data in terms of coupling across brains instead of responses of a brain to a stimulus[25].
Repetition suppression fMRI. To address the question of whether the same neurons
are activated within a voxel in action execution and perception, some have turned to a
method termed repetition suppression fMRI (rsMRI). The rationale behind this method is that
if we present stimulus A, we measure a BOLD response of a certain magnitude in a voxel. If
this stimulus is preceded by another stimulus, A’, that activates the same neurons in the
voxel, the neuron might become fatigued, and respond less strongly to A. If it was preceded
by a stimulus B, that recruits a different set of neurons, this repetition suppression should not
occur. Hence, a number of groups presented participants with movies of different actions and
had them do similar actions, manipulating the order so that the observation of an action was
either preceded by the execution of the same or a different action, and vice versa. The ventral
premotor cortex, the dorsal premotor cortex and inferior parietal lobe show reduced activity
to the execution of an action that follows the observation of the same action [26, 27] and vice
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versa[26, 28]. These results are therefore compatible with these brain regions containing
mirror neurons. However, rsMRI is plagued with numerous problems, that caution the
interpretation of these results (see [29] for a dispassionate review). First, and foremost, the
physiological basis of rsMRI is not understood. With fMRI being sensitive to synaptic
metabolism[17], repetition suppression could reflect repeated activation of the same mirror
neurons within the voxel showing suppression, as often assumed, or it might reflect changes
in synaptic input to the voxel originating from mirror neurons elsewhere. Accordingly, rsMRI
is certainly not a panacea to localize mirror neurons. In our own recordings of mirror neurons
in monkeys(e.g. [5]), we examined if mirror neurons show repetition suppression, and found
their firing rate not to. Therefore, if voxels show rsMRI, this effect is unlikely to reflect
repetition suppression in neural firing rates, and some vascular or synaptic effect must be
responsible for the rsMRI, making it likely that rsMRI may mislocalize mirror neurons, as it
does for other types of neurons[29]. Second, if a neuron receives separate synaptic input from
brain regions controlling actions and responding to sensory stimuli, the neuron might be
mirror and yet have none of its synaptic input be shared between the two modalities and thus
provide no basis for synaptic rsMRI effects. Third, while traditional fMRI responses already
rely on a small fraction of the MRI signal (<1% in most cognitive tasks), rsMRI works on an
even smaller fraction of that already small fMRI signal. Accordingly, rsMRI has very low
statistical power, and most studies (n<20) are underpowered to detect such small effects,
hence it is not surprising that rsMRI effects are unreliable and often fail to replicate, and
rsMRI papers therefore should refrain from interpreting a lack of significant repetition
suppression as evidence for a lack of mirror neurons, but these basic statistical considerations
have sometimes not been fully understood[27]. All in all, the use of rsMRI has therefore led
to findings compatible with the presence of mirror neurons in humans, but it is difficult to
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interpret these results due to our poor understanding of the physiology of that method and its
limited statistical power.
Transcranial magnetic stimulation (TMS). TMS has been used in two ways to
explore the existence of vicarious motor activations in humans. When single pulses of TMS
(spTMS) are given over the primary motor cortex (MI), they trigger muscle activity in the
corresponding body parts. These motor evoked potentials (MEPs) can then be quantified
using myographic recordings from relevant muscles. If some input to MI were to change the
excitability of that region, for instance because the sight of an action triggers motor programs
to perform that action, the same TMS pulse would trigger a larger MEP in muscles involved
in performing that action. A growing number of studies show that excitability in MI is
increased when listening to or viewing the actions of others specifically for the muscles
involved in the observed actions (see [30] for an excellent review of the topic). Interestingly,
if spTMS is applied at various points in time during the observation of a grasping action, the
amount of MEP facilitation in the observer is correlated with the state of the corresponding
muscles in the observed agent[31]. These findings add to the existing fMRI literature in
showing that humans trigger motor programs in a way that mirrors the timing of other
people’s actions, and thereby complement the recent neuroimaging findings suggesting a
similar resonance[23, 24]. However, they do not tell us where in the brain action perception
and execution are matched, but rather measure the distal impact this common coding has on
the output stage of the motor system. To explore which brain regions are necessary for action
observation to recruit motor programs, TMS can also be used to interfere with the functioning
of particular brain regions and see the impact this has on the perception of the actions and on
MEP facilitation. Results indicate that the ventral premotor cortex and the somatosensory
cortex seem to be necessary sources for visual MEP facilitation[32], and that the perception
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of actions is impaired after interference with premotor regions [33], and as we will show in
this presentation, somatosensory regions.
Mu-suppression. EEG and MEG measure, through the scalp, currents that are
generated by synchronous activity of populations of neurons. Two rhythms have been
associated with the motor system: the mu (8-12Hz) and beta (~20Hz) rhythm. Both rhythms
have more power while the subject is at rest than when a participant performs an action,
making them similar to the alpha rhythm in the visual system that is strongest when
participants close their eyes. The power in these frequency bands is thus an indicator of how
active the sensory-motor system is. Interesting, perceiving the actions of others is linked with
changes in the power-spectrum of the EEG and MEG signal that resemble those associated
with executing similar actions, suggesting that viewing the actions of others triggers activity
(and thus depresses mu and beta power) in the sensorimotor system. This was first observed
in 1954, four decades before the discovery of mirror neurons in the monkey, by Gastaut and
Bert in a surprisingly modern experiment: “[the rolandic mu-rhythm] is blocked when the
subject performs a movement […]. It also disappears when the subject identifies himself with
an active person represented on the screen. […] During a sequence of film showing a boxing
match. […] less than a second after the appearance of the boxers all type of rolandic activity
disappears in spite of the fact that the subject seems completely relaxed”[34, p439]. Once
mirror neurons were described, this phenomenon received renewed interest, with a number of
experiments now confirming the visual suppression of mu power in EEG [35-39]. Most
authors interpreted these findings as suggesting that mu-suppression reflected the distal effect
on MI of mirror neuron activity in the ventral premotor cortex, where mirror neurons had
been first described in the monkey. To test this notion, we simultaneously measured mu-
power and fMRI BOLD activity while participants viewed and executed different actions,
and found that dorsal premotor and SI activation were actually the most likely source of mu-
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suppression[40]. Although these regions have been regularly associated with vicarious motor
activations, the ventral premotor cortex was not tightly correlated with trial-by-trial mu-
suppression. This finding is encouraging in that it shows that EEG, which is more suitable
than fMRI to measure brain activity in young individuals, is a valid measurement of vicarious
motor activations, but refines current thinking by showing that it does not necessarily
measure ventral premotor activation.
Single cell recordings. The only study so far to look at mirror neurons in humans
directly by using single cell recording was performed by Mukamel et al. [41]. Because the
recordings were performed to localize epilepsy, they could not choose the location of
electrodes, and had to explore the medial cortical surface around SMA/preSMA and the
medial temporal lobe. Due to the clinical constrains, they only had limited time to test each
neuron, and therefore could not specify the selectivity of neurons in detail. However, in SMA
and in the medial temporal lobe, they found a small number of neurons that responded
specifically when participants performed one of multiple actions, and when observing the
same action, thereby providing the most direct evidence for mirror neurons in humans, and
confirmed our claim, driven by fMRI findings, that the vicarious motor activations extend
beyond the ventral premotor and posterior parietal lobe to encompass regions such as the
SMA[16]. Interestingly, some neurons in the SMA behaved like anti-mirror neurons,
showing activation during action execution, but inhibition during action observation. Such
neurons could serve to suppress automatic imitation of observed actions.
Neurological lesions. While no doubt remains about the existence of mirror neurons
in humans, monkeys and birds, the exact function of these neurons in the brain remains less
clear. Recently, a number of studies therefore explored the idea that mirror neurons could
help us perceive the actions of others by testing whether patients with lesions in regions
associated with vicarious motor activations would be impaired in the perception (visual or
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auditory) of actions of other people. Participants that suffer from limb apraxia have
difficulties in deciding whether a hand gesture they observe is meaningful or meaningless,
with performance in this perceptual task being correlated with their capacity to imitate
intransitive gestures [42]. Lesion analysis showed that patients with limb apraxia who
showed more action recognition difficulties were more likely to have lesions in ventral
premotor cortex. The fact that many patients with apraxia and lesions in the MNS were still
able to perceive some of the gestures correctly shows that the MNS is not the only system
that can help recognize actions, but the significant deficits observed in the majority of
patients shows that it can significantly contribute to action recognition. In addition,
participants with apraxia also have difficulties in recognizing the sound of other people’s
actions, with those suffering from apraxia of the mouth more impaired in recognizing mouth
action sounds, and those suffering from apraxia of the limb more impaired in recognizing
hand action sounds [43], in agreement with the somatotopic organization of the auditory
MNS [20]. The ventral premotor cortex is also involved in mirroring a very specific type of
action: facial expressions [44], and lesions to this area impair the recognition of facial
expressions [45].
Vicarious Somatosensation
Somatosensation involves the processing of tactile, proprioceptive and nociceptive
information. Traditionally, in humans and monkeys, the term ‘somatosensory cortices’ proper
refers to the anterior parietal cortex and the upper bank (operculum) of the lateral sulcus that
process tactile, proprioceptive and nociceptive information. The term ‘somatosensory
system’, on the other hand, refers to all the brain regions involved in processing
somatosensory information, and refers to the somatosensory cortices proper plus the insula
and the rostral cingulate cortex that are thought to process the affective value of
somatosensory stimuli[46], although it becomes increasingly apparent, that the
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somatosensory cortices proper also play an important role in processing affective value,
particularly when it comes to gentle social touch.
The anterior parietal cortex consists of four parallel sectors: the classical
cytoarchitectonic areas 3a, 3b, 1 and 2 of Brodmann. In humans, Brodmann Area (BA) 3a
and 3b roughly correspond to the posterior bank of the central sulcus, BA 1 to the crown of
the postcentral gyrus and BA 2 to the anterior bank of the postcentral gyrus (Fig. 1a,b). BA
3a and 3b are sometimes grouped as BA3. Each of these four areas is known to constitute a
separate representation with different connections and functions (see ref [46] for a review).
Accordingly, the term ‘SI’ is now used to refer to BA3a+3b+1+2 when it is unclear to which
of the subregions a statement applies or when it applies to all four.
BA 3a receives proprioceptive information and has close anatomical connections with
the motor cortex. BA 3b is the primary area for tactile processing, and it receives its major
activating inputs from the ventroposterior nucleus (VP) of the thalamus. BA 3b also receives
input from nociceptive neurons in the spinal cord and brain stem[47]. BA 1 receives strong
activating inputs from BA 3b, and thus is thought to be involved in a secondary cortical stage
of tactile processing. BA 2 receives inputs from BA3a, BA 3b and 1 and therefore constitutes
a third level of cortical processing of tactile and proprioceptive information[48]. This tactile
information is combined with proprioceptive inputs from the thalamic nucleus VPS. Thus,
neurons in BA 2 are especially responsive when objects are actively explored or manipulated
with the hands so that tactile and proprioceptive afferent information is combined in a
process we will term haptic[49]. The connections between areas of SI are reciprocal.
Importantly, BA 2 also has direct, reciprocal connections with regions of the fundus of the
intraparietal sulcus (area VIP) and the inferior parietal lobule (areas PF/PFG in particular)
which combine visual, auditory and somatosensory information[48, 50-52]. Some cells in
VIP respond both when a monkey is touched and when it sees someone else being touched in
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a similar way[53] whereas some neurons in PF/PFG respond both when the monkey performs
a goal-directed action and when it sees another individual perform a similar action[7].
Moreover, these posterior parietal regions are thought to constitute the main source of visual
and auditory information to mirror neurons in the premotor cortex[54]. The fact that these
regions also project to BA2 makes it plausible that BA2 could demonstrate vicarious
activations in response to goal-directed actions of others. From SI, somatosensory
information is sent to SII; these connections are reciprocal, allowing areas involved in early
processing stages to be influenced by areas involved in later processing stages.
SII, which lies on the parietal operculum (OP), has now been divided into two sub-
regions termed S2 and PV (the parietal ventral area) in both monkeys and humans[55], which
correspond to distinct architectonic fields, OP1 and OP4, respectively[56]. S2 and PV receive
inputs from all four areas of SI and are therefore involved in a third or forth level of
processing. S2 and PV have similar afferent and efferent cortical connections[57] with
cortical regions of the operculum and with a number of brain regions with cells that respond
to visual and auditory input (e.g. PF/PFG and VIP[51, 52], both of which also provide input
to BA2), secondary auditory areas that are also responsive to somatosensory stimuli[58], and
the insula[59].
For nociception, classically, SI and SII are thought to process the sensory
discriminative aspects (i.e. the intensity and location) of pain[60]. This occurs in parallel with
the more affective/motivational processing of nociceptive input that is thought to take place
in the insula and the rostral cingulate gyrus[60]. The posterior insula receives thalamic input
associated with the spinothalamic pathway[61], and cortical inputs from adjoining and nearby
cortical areas. Different sectors of the posterior insula seem to be involved in the appreciation
of pain, temperature, itch, and pleasant touch[62], but do not receive pronounced auditory or
visual input[59]. This information is then relayed to more anterior sectors of the insula, where
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it is integrated with input from the frontal lobe, all sensory modalities and limbic
structures[59, 63]. The rostral cingulate cortex also receives nociceptive input from more
lateral nuclei in the thalamus (VMpo, MDvc, Pf and CL) and integrates this information with
highly processed information from various cortical areas[60].
Vicarious Tactile Activations
A number of fMRI studies now show that somatosensory cortices might also be vicariously
activated while viewing others be touched. In the first such experiment, we caressed the legs
of participants in a scanner after the same participants had watched movie clips of either
other people’s legs being touched by a rod or, as control stimuli, movies of the same rod
moving too far away from the same legs to touch them. Being touched activated the leg
representations in both SI and SII. Importantly, viewing other people being touched
compared to the control condition also activated SII (but not SI)[64]. SII was even activated
when participants watched objects (e.g. rolls of paper) being touched compared to movies of
the objects not being touched[64]. Other studies also showed SII activity in participants
seeing the hands[65, 66] or the neck and face[67] of other people being touched in movie
clips. One study also replicated the SII activation in response to seeing objects being touched
[65] but another did not[67]. That SII responds to the sight of humans and, sometimes,
objects being touched, and the fact the neurons in SII have very large receptive fields[68],
suggest that vicarious activation in SII could convey a simulation of the quality of touch one
would feel if one were touched in a similar way, rather than the precise body location on
which the touch occurred. Interestingly, watching tactile stimulation of more erogenous zones
of the body in pornographical movies also activates SII vicariously[69-71].
In contrast to SII, BA3 was never activated during the observation of touch and BA2
and BA1 were only activated if the stimuli showed a human hand delivering the touch[67] or
when the task focused attention on the action of touching[66], and it is likely that this
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activation vicariously represent the hand delivering the touch rather than the sensations of the
person being touched, for the activations fall in the hand region even when the stimuli
showed a face being touched[67], and because SI is more activated when seeing a hand
compared to an object touch a body part [65]. Bufalari et al.[72] electro-stimulated the
median nerve of their participants to provide a precisely timed somatosensory input, and
measured the resulting sensory evoked potentials (SEP) on the scalp. Somatosensory evoked
potentials, measured with EEG from participants watching movie clips of a hand being
touched by a cotton swab showed that components associated with BA3 were not influenced
by this visual stimulus, whereas later components (e.g. the P45) sometimes associated with
SII, were[72].
The fact that BA3a and 3b are only recruited when we ourselves are being touched
could account for why participants that see other people be touched can vicariously activate
SII, as if they would be touched themselves, without being confused about who is actually
being touched. About 1% of people however experience a vivid sensation of touch on their
own body when they see the body of others being touched[73]. This effect is so automatic
that these so-called ‘mirror touch synaesthetes’ often misreport the location on which they are
touched if they simultaneously see another person being touched[73, 74]. Blakemore et al.
measured brain activity in one such synaesthete and found that she differed from controls in
that she activated her SI (probably including BA3) and SII more strongly than controls when
seeing movies of other people being touched[67]. This suggests that the degree of vicarious
activations in somatosensory brain regions, and in particular the involvement of BA3, can
determine the vividness with which one empathically shares what other people go through.
Vicarious Haptics and Proprioceptive Activations
In humans, lesions to SI lead to devastating impairments in motor control[75]. Does SI also
help us perceive the actions of others? Historically, mirror neurons have been reported in
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regions involved in motor planning: the ventral premotor cortex[1, 5, 6, 9, 76, 77] and the
posterior parietal cortex (area PF/PFG[4, 7] and the anterior intraparietal sulcus[9]).
Consequently, most theoretical papers focus on the motor (as opposed to the somatosensory)
side of action simulation[78-84]. However, the finding that half the neurons in the ventral
premotor cortex also respond to somatosensory stimulation[85] suggests that the mirror
neuron system may have tight functional links with the somatosensory cortices. As
mentioned above, our experiment mapping vicarious motor activations (i.e. voxels that were
active during observation and execution of goal-directed actions) without smoothing the data
revealed such activations also in somatosensory cortex, BA2 in particular, with this regions
containing more vicariously activated voxels and in more participants than did the ventral
premotor cortex. SII also contained vicarious activations (albeit fewer than BA2). Reviewing
all six studies examining action observation and execution using fMRI [86]confirmed that
BA2 is consistently active during action observation — as consistently as the ventral
premotor cortex. A quantitative metaanalysis of action observation experiments confirmed
this result[15]. In contrast to BA2, more-anterior sectors of SI are rarely and only weakly
recruited during the observation of other people’s actions. Compared with the observation of
passive touch, SII is more weakly recruited during action observation. Hearing the sound of
other people’s actions also strongly activates BA2 and, to a lesser extent, SII[87, 88].
Seeing hand movements with more joint stretching activates BA2 more strongly[89],
and deactivating BA2 using TMS reduces motor evoked potentials in the hand when seeing
such extreme joint stretching[32]. BA2 is more active when viewing hands manipulate
objects (e.g. grasping a cup) compared to actions that do not involve objects[90, 91].
Additionally, viewing someone move a heavier object activates BA2 more strongly than
viewing someone move a lighter object [92]. Together, and in accordance with the
convergence of tactile and proprioceptive input in BA2, BA2 might be particularly involved
18
in vicariously representing the haptic combination of tactile and proprioceptive signals that
would arise if the participant manipulated the object in the observed way (Fig. 2b). This
vicarious representation of haptic aspects of actions in BA2 then adds to the vicarious
representations of passive touch in SII.
A limitation of fMRI studies is that the activity of a particular brain region during
both the execution and the perception of an action does not guarantee that both scenarios
involve activity in neurons representing the same information (e.g. a particular haptic
sensation or motor program). However, the somatotopic organization of SI allows one to link
the location of activity (measurable with fMRI) to the representation of a particular body part.
One can therefore be confident that the observation of hand actions indeed specifically
triggers the representation of hand actions in BA2. Additionally, executing hand and mouth
actions causes activity in dorsal and ventral SI, respectively, and perceiving mouth and hand
actions triggers vicarious activity in the corresponding locations[87]. Multi-voxel pattern
classification of activity data in SI during action perception can identify the body part that
was used for an action performed by another individual[93]. Additionally, seeing people
touch different objects generates differentiable patterns of activity in SI[94]. Together, these
data suggests that vicarious BA2 activity could provide fine-grained, somatotopically specific
representations of other people’s actions.
The simulation of actions would thus involve both simulating the motor output that
would be necessary for performing the observed action (as represented in the classic
premotor and posterior parietal mirror neuron containing regions) and simulating the haptic
somatosensory input that would accompany performing those actions. To test the
contribution of vicarious SI activations to the haptic aspects of other people’s actions, we
showed participants hands lifting boxes of different weights, and asked them to judge the
weight of these boxes. Participants were less accurate at this task if TMS was used to
19
interfere with brain activity in SI (Paper under review), and interference with activity in
premotor cortex has a similar effect[33]. Such a link between the motor and somatosensory
system during action observation would be in holding with, and might employ the same
neural mechanisms as, that during action execution, where the expectation of touch is a
fundamental component of forward models in goal-directed motor control[95, 96].
Facial expressions are a special type of action. Experiments that have examined the
neural structures involved both in the observation and the execution of dynamic facial
expressions concur that, akin to observing hand actions, observing the facial expressions of
others also vicariously activates ventral sectors of BA2 and/or SII that are involved in sensing
self-produced facial expressions[97-99]. Real and virtual (TMS) lesions in these
somatosensory face representations also impair the recognition of facial expressions[45, 100],
suggesting that vicarious somatosensory representations of what it feels like to move the face
in the observed way contribute to the recognition of other people’s facial expressions.
Vicarious Nociceptive Activations
If we see our partner’s face expressing intense pain, we feel deeply distressed. If we see her
cut her finger with a sharp kitchen knife, we not only feel distress, we often feel compelled to
grasp our own finger. About a third of people feel pain on the corresponding part of their own
body when they see certain injuries of other people[101]. Neuroimaging research is now
starting to shed light on this multifaceted nature of empathic pain. In brief, this research
shows that if all we know is that another person is in pain, we vicariously recruit brain
regions involved in the affective experience of pain: the anterior insula and rostral cingulate
cortex[102-107]. Whenever our attention is directed to the somatic cause of the pain of
others, somatosensory cortices also become vicariously activated in most experiments [108-
115].
20
When observing photographs of injuries (e.g. an athlete braking his leg), about one
third of the population reports feeling pain on the corresponding part of their own body. The
remainder reports negative feelings without a sense of somatic pain. fMRI showed that SI/SII
vicarious activity was significantly triggered by such images only in those participant
experiencing localized vicarious pain[101]. This provides further support that vicarious SI
and SII activity adds a somatic dimension to social perception.
Although it is difficult to determine from the limited details available from published
activation tables which parts of SI are recruited by the observation of other people’s body-
parts being harmed, of the eight fMRI studies that examined the observation of hands or feet
in painful situations, six explicitly report vicarious activations in coordinates that correspond
to BA2 or BA1[108-111, 113, 114], whereas only one explicitly mentions activation in
BA3[110]. It therefore seems that, as for touch and action, vicarious activity for somatic pain
is restricted to the higher levels of somatosensory processing (i.e. regions that receive direct
auditory or visual input), whereas BA3 remains ‘private’, only being activated by the first-
hand experience of pain. This difference could again account for why seeing the pain of
others can be touching in a localized way without causing confusion about who was being
hurt (i.e. the observer or the observed person).
Taken together these data indicate that we can share the pain of others in two ways. If
all we know is that the observed person is in pain, we share the affective aspects of his/her
distress through vicarious activity in the anterior insula and rostral cingulate cortex. If, on the
other hand, we focus on the somatic causes of that pain, we additionally share its somatic
consequences by vicarious recruiting BA1/2 and/or SII.
Vicarious Emotional Activity
Brain regions associated with emotions have also been found to be vicariously
activated while participants perceive the emotional states of others. Viewing facial
21
expressions that signal emotions, be it disgust [116, 117], happiness [97, 116] or a
combination of different emotions [118], activates regions of the anterior Insula and adjacent
Frontal Operculum (jointly referred to as IFO) involved in experiencing similar emotions as
triggered by gustatory [116] or olfactory [117] stimuli. These findings dovetail with findings
that the vision of stimuli that suggest other people’s pain (e.g. facial expressions of pain,
symbols indicating that someone else is in pain or body parts in painful situations), trigger
activity in this same region[119]. Together these findings suggest, that representations of
emotional bodily states in the IFO can be triggered by many sources of information that
signal that another individual is experiencing similar emotional states.
Emotional empathy seems not to be restricted to primates. In the late 1950s, Church
exposed rats to other rats receiving electroshocks, and found that the rats would press a level
for reward less frequently in conditions were they were exposed to other rats distress,
showing that they were somehow affected by the distress[120], and the authors interpreted
their findings as suggesting that the witness rats actually experienced fear, vicariously
triggered by the distress of the other rat, that interfered with their operant behavior. Recently,
we came to a similar conclusion. We split rats into four groups, that had either experienced
electroshocks in the past, or not, and that now witness another rat receive an electroshock, or
not. We found that rats previously exposed to electroshocks showed (vicarious) freezing
behavior, a sign of fear, when they witnessed another rat experience an electroshock[121].
This behavior was not simply triggered by distress vocalizations (the playback of which
failed to trigger a similar effect), but relied on perceiving the complex behavior of a rat that
reacts to electroshocks. None of the other groups showed such elevated freezing. This
suggests that prior experience is a necessary condition for vicarious fear in rats, and shows
that vicarious emotional representations already exist in rodents. In the early 1960s, Rice and
Gainer further showed that a rat would vigorously press a level to release another rat from a
22
distressing suspender, showing evidence that vicarious distress might motivate prosocial
behavior in rodents as well[122]. This finding was recently confirmed by a study showing
that rats will work to open restraining tubes to release another rat[122], and are even willing
to give up small quantities of highly palatable food to help the other rat.
Unlike the actions of other individuals, which can be directly perceived by others, we
cannot directly see the emotions of others but have to deduce their emotions from their
actions (e.g. facial expressions), visible causes (e.g. a syringe penetrating a hand), or more
arbitrary cues such as language (e.g. ‘I’m very sad today’). Anatomically, the IFO receives
input from the prefrontal cortex, the motor system and all sensory modalities. Functional
connectivity analyses now increasingly try to disentangle which of these sources of input
trigger vicarious activity in the IFO in specific cases. While viewing facial expressions,
premotor brain regions involved in producing similar facial expressions [44, 97, 118] seems
to play an important role in triggering activity in the IFO [123]. While deducing pain from
viewing bodily causes, the superior temporal sulcus seems to play a dominant role[124].
Reading about emotions finally, Broca’s area, the temporal pole and the SMA play critical
roles[125]. Neurological studies confirm that disrupting activity in the IFO or the premotor
cortex impairs the recognition of other people’s emotions from facial expressions [45, 126,
127] but further suggest that impairing the primary and secondary somatosensory
representations of the face that become active while feeling the consequences of our own
facial expressions [44, 97] also impairs facial affect recognition. Together, these data suggest
that the IFO may work in concert with brain regions involved in the mirror neuron system
and vicarious somatosensory activations to trigger representations of emotions that match
those of the people around us.
In the above reviewed work, participants often view the emotions of people they have
never met, and activate representations of their own emotions. This suggests that the brain
23
spontaneously triggers vicarious representations when seeing the emotions of others. The
strength of these vicarious representations correlates with how empathic participants report
being in life[102, 116], suggesting that these vicarious activations could be a neural correlate
of what people call empathy. Importantly, a number of factors can however reduce this
spontaneously occurring vicarious activations. If one knows that the other person has been
unfair [103], belongs to another race[128] or supports a rivaling foot-ball team[129],
vicarious activations are reduced.
Vicarious Motor, Somatosensory and Emotional Activations and Cognition
Together, the abovementioned evidence therefore suggests that humans, monkeys and
birds show evidence of vicariously activating their own actions when they see or hear those
of others. At least humans additionally activate representations of their own sensations and
emotions when they see perceive those of others. Together, this shows that when we perceive
what others do, or what they experience, we not only recruit visual and auditory brain regions
that encode what we see and hear: we additionally trigger representations of how we would
perform similar actions or feel similar sensations and emotions. In a way we slip under the
skin of the people we witness, and share their actions, sensations and emotions. Lesions in
brain regions that show such vicarious activations impair our capacity to optimally feel what
others do and feel, suggesting that these vicarious representations are an important
mechanism of social cognition. Of course, we cannot magically sense what goes on in others.
Instead, vicarious activations are a projection of what we would do or feel, onto others. The
projective nature of this process becomes particularly striking when looking at cases in which
participants view robotic actions. Our humans participants knew that the robot in the videos
is not endowed with a premotor cortex or somatosensory regions resembling that of humans.
Hence, an accurate representation of what goes on in the robot’s CPU should not involve the
recruitment of premotor or somatosensory brain regions in the viewer. If viewers project their
24
own intentional actions and sensations, on the other hand, one would expect to measure brain
activation in the viewer encompassing premotor and somatosensory regions, and this activity
should be as strong as when viewing humans do similar actions. The evidence fully supported
the projection hypothesis, with premotor and somatosensory activity being as strong when
viewing robots and humans perform actions[130]. Further evidence for projection stems from
the fact that people born without hands and arms activate representations involved in
controlling their foot and mouth when viewing the hand actions of others[131]. Hence,
vicarious activations should be considered a heuristic, in which we use the only motor
programs, somatosensory representations and emotions we have ever experienced, namely
our own, to perceive those of others[132]. Recent work evidencing information flow from
regions involved in various motor activations onto visual brain regions further suggests that
vicarious motor representations may serve to predict the future actions of others through the
forward models so important for motor control[133].
How do vicarious activations develop? Since an actor is also spectator and auditor of
her own actions, during hand actions for instance, parietal and pre-motor neurons controlling
the action fire at the same time as neurons in the visual and auditory cortex that respond to
the observation and sound of this specific hand action (some of which irrespective of the
view point). These sensory and motor neurons that fire together would wire together, i.e.
strengthen their connections through Hebbian synaptic potentiation [54] (see also Heyes et al.
[134] for a similar model based on association learning). After repeated self-
observation/audition, the motor neurons in the premotor and parietal regions would now
receive such strong synaptic input from sensory neurons responding to the sight and sound of
the action, that they would become mirror. The same pairing between execution and
observation would also occur in cases in which an individual is imitated by another [134-
136]. For instance, a child cannot observe its own facial expressions, but the adult who
25
imitates the child's expression would serve as a mirror, triggering in the child's STS an
activity pattern, representing what the expression sounds and looks like, that becomes
associated with the pre-motor cortex activity producing the expression that was imitated
[136]. Hebbian learning could explain the emergence of the MNS in infants and its plasticity
in adulthood. This perspective does not preclude the possibility that some genetic factors may
guide its development. Genetic factors could for instance canalize [137] Hebbian learning by
equipping the baby with a tendency to perform spontaneous and cyclic movements and to
look preferentially at biological motion congruent with its actions to provide the right activity
patterns for Hebbian learning to occur. What is important in this perspective is that the MNS
is no longer a specific social adaptation, that evolved to permit action understanding, but is a
simple consequence of sensory-motor learning that has to occur for an individual to be able to
visually control his own actions [135, 136, 138]. Note that due to sensorimotor latencies,
there is a systematic time-lag between motor activity and sensory consequences that endow
this Hebbian learning with predictive properties.
In contrast to early works that contrast embodied and cognitive views of social
cognition, researchers increasingly embrace the fact that vicarious activations in the motor,
somatosensory and emotional system interact and sometimes depend on other, more
cognitive brain systems involved in attention, mentalizing and cognitive control: (a)
Directing attention towards or away from actions modulates activity in vicarious motor
representations[139]. (b) Asking participants to reflect about the intentions behind observed
actions triggers activity in mentalizing, in addition to motor, brain regions[8, 140], suggesting
that motor simulation could provide an input to ‘mentalizing’ brain regions[141]. (c) If
people are asked to switch from doing the same to doing the opposite of another individual to
achieve a common goal, cognitive control brain regions activate alongside mirror
regions[142]. These regions are probably necessary to determine, based on current goals,
26
whether mirror representations of the observed actions will be executed or whether
representations of complementary actions get to be executed. In addition, empathy with the
emotions of others can be modulated by prior knowledge about the fairness of the victim,
cognitive appraisal and perspective taking (see [143] for a review). Finally, in a recent
experiment analyzing the information flow between two communicating brains, we could see
that regions involved in vicarious motor activations and those involved in mentalizing
cooperate to represent information about the state of the sender’s brain[23].
Conclusions
In summary, the last years have seen an explosion of evidence to suggest that
vicarious activations are not restricted to monkeys, actions, or the premotor cortex: (a)
humans and birds have mirror neurons, (b) many other brain regions involved in motor
execution seem to be vicariously activated during the observation of other people’s actions,
and (c) in addition to motor representations, our brain also seems to vicariously trigger
somatosensory and emotional representations while viewing others being touched, perform
actions, or experience emotions. Instead of a vision in which the ventral premotor cortex is a
singular brain region endowed with a unique mirror property that would single-handedly shed
light onto the inner lives of others, these findings draw a less monochromatic picture:
vicarious activity can be measured in many brain regions - including motor, somatosensory
and emotional cortices. The flexible interplay of these circuits with brain regions associated
with attention, cognitive control, and mentalizing may be what allows us to feel and
empathize with the inner lives of others. In support of this idea, lesions in somatosensory,
insular and premotor regions all seem to impair our capacity to feel the emotions of others
[45, 126, 127]. Understanding the precise function of each of the many vicariously
recruitable brain regions in social perception however remains an important challenge for
future research.
27
Notes
The research was supported by a VENI grant to VG and NIHC grants to CK.
References
1. Gallese, V., Fadiga, L., Fogassi, L., and Rizzolatti, G. (1996). Action recognition in the
premotor cortex. Brain 119 ( Pt 2), 593-609.
2. Keysers, C. (2009). Mirror neurons. Current Biology 19, R971-R973.
3. Graziano, M.S., Taylor, C.S., and Moore, T. (2002). Complex movements evoked by
microstimulation of precentral cortex. Neuron 34, 841-851.
4. Fogassi, L., Ferrari, P.F., Gesierich, B., Rozzi, S., Chersi, F., and Rizzolatti, G. (2005).
Parietal lobe: from action organization to intention understanding. Science 308, 662-
667.
5. Keysers, C., Kohler, E., Umilta, M.A., Nanetti, L., Fogassi, L., and Gallese, V. (2003).
Audiovisual mirror neurons and action recognition. Exp Brain Res 153, 628-636.
6. Kohler, E., Keysers, C., Umilta, M.A., Fogassi, L., Gallese, V., and Rizzolatti, G.
(2002). Hearing sounds, understanding actions: action representation in mirror neurons.
Science 297, 846-848.
7. Rozzi, S., Ferrari, P.F., Bonini, L., Rizzolatti, G., and Fogassi, L. (2008). Functional
organization of inferior parietal lobule convexity in the macaque monkey:
electrophysiological characterization of motor, sensory and mirror responses and their
correlation with cytoarchitectonic areas. Eur J Neurosci 28, 1569-1588.
8. Thioux, M., Gazzola, V., and Keysers, C. (2008). Action understanding: how, what and
why. Curr Biol 18, R431-434.
28
9. Fujii, N., Hihara, S., and Iriki, A. (2008). Social cognition in premotor and parietal
cortex. Soc Neurosci 3, 250-260.
10. Cisek, P., and Kalaska, J.F. (2004). Neural correlates of mental rehearsal in dorsal
premotor cortex. Nature 431, 993-996.
11. Shepherd, S.V., Klein, J.T., Deaner, R.O., and Platt, M.L. (2009). Mirroring of
attention by neurons in macaque parietal cortex. Proc Natl Acad Sci U S A 106, 9489-
9494.
12. Keysers, C., and Gazzola, V. (2009). Expanding the mirror: vicarious activity for
actions, emotions, and sensations. Curr Opin Neurobiol 19, 666-671.
13. Prather, J.F., Peters, S., Nowicki, S., and Mooney, R. (2008). Precise auditory-vocal
mirroring in neurons for learned vocal communication. Nature 451, 305-310.
14. Keller, G.B., and Hahnloser, R.H. (2009). Neural processing of auditory feedback
during vocal practice in a songbird. Nature 457, 187-190.
15. Caspers, S., Zilles, K., Laird, A.R., and Eickhoff, S.B. (2010). ALE meta-analysis of
action observation and imitation in the human brain. Neuroimage 50, 1148-1167.
16. Gazzola, V., and Keysers, C. (2009). The observation and execution of actions share
motor and somatosensory voxels in all tested subjects: single-subject analyses of
unsmoothed fMRI data. Cereb Cortex 19, 1239-1255.
17. Goense, J., Whittingstall, K., and Logothetis, N.K. (2012). Neural and BOLD responses
across the brain. Wiley Interdisciplinary Reviews-Cognitive Science 3, 75-86.
18. Molenberghs, P., Cunnington, R., and Mattingley, J.B. (2012). Brain regions with
mirror properties: a meta-analysis of 125 human fMRI studies. Neuroscience and
biobehavioral reviews 36, 341-349.
19. Etzel, J.A., Gazzola, V., and Keysers, C. (2009). An introduction to anatomical ROI-
based fMRI classification analysis. Brain Research 1282, 114-125.
29
20. Gazzola, V., Aziz-Zadeh, L., and Keysers, C. (2006). Empathy and the Somatotopic
Auditory Mirror System in Human. Current Biology 16, 1824-1829.
21. Oosterhof, N.N., Wiggett, A.J., Diedrichsen, J., Tipper, S.P., and Downing, P.E.
(2010). Surface-based information mapping reveals crossmodal vision-action
representations in human parietal and occipitotemporal cortex. J Neurophysiol 104,
1077-1089.
22. Prinz, W. (1997). Perception and action planning. Eur. J. Cogn. Psychol. 9, 129-154.
23. Schippers, M.B., Roebroeck, A., Renken, R., Nanetti, L., and Keysers, C. (2010).
Mapping the information flow from one brain to another during gestural
communication. Proc Natl Acad Sci U S A 107, 9388-9393.
24. Stephens, G.J., Silbert, L.J., and Hasson, U. (2010). Speaker-listener neural coupling
underlies successful communication. Proc Natl Acad Sci U S A 107, 14425-14430.
25. Hasson, U., Ghazanfar, A.A., Galantucci, B., Garrod, S., and Keysers, C. (2012). Brain-
to-brain coupling: a mechanism for creating and sharing a social world. Trends Cogn
Sci 16, 114-121.
26. Kilner, J.M., Neal, A., Weiskopf, N., Friston, K.J., and Frith, C.D. (2009). Evidence of
mirror neurons in human inferior frontal gyrus. J Neurosci 29, 10153-10159.
27. Lingnau, A., Gesierich, B., and Caramazza, A. (2009). Asymmetric fMRI adaptation
reveals no evidence for mirror neurons in humans. Proc Natl Acad Sci U S A 106,
9925-9930.
28. Chong, T.T., Cunnington, R., Williams, M.A., Kanwisher, N., and Mattingley, J.B.
(2008). fMRI adaptation reveals mirror neurons in human inferior parietal cortex. Curr
Biol 18, 1576-1580.
29. Bartels, A., Logothetis, N.K., and Moutoussis, K. (2008). fMRI and its interpretations:
an illustration on directional selectivity in area V5/MT. Trends Neurosci 31, 444-453.
30
30. Fadiga, L., Craighero, L., and Olivier, E. (2005). Human motor cortex excitability
during the perception of others' action. Curr Opin Neurobiol 15, 213-218.
31. Gangitano, M., Mottaghy, F.M., and Pascual-Leone, A. (2001). Phase-specific
modulation of cortical motor output during movement observation. Neuroreport 12,
1489-1492.
32. Avenanti, A., Bolognini, N., Maravita, A., and Aglioti, S.M. (2007). Somatic and motor
components of action simulation. Curr Biol 17, 2129-2135.
33. Pobric, G., and Hamilton, A.F. (2006). Action understanding requires the left inferior
frontal cortex. Curr Biol 16, 524-529.
34. Gastaut, H.J., and Bert, J. (1954). Eeg Changes during Cinematographic Presentation -
(Moving Picture Activation of the Eeg). Electroencephalography and Clinical
Neurophysiology 6, 433-444.
35. Cochin, S., Barthelemy, C., Lejeune, B., Roux, S., and Martineau, J. (1998). Perception
of motion and qEEG activity in human adults. Electroencephalogr Clin Neurophysiol
107, 287-295.
36. Cochin, S., Barthelemy, C., Roux, S., and Martineau, J. (1999). Observation and
execution of movement: similarities demonstrated by quantified
electroencephalography. Eur J Neurosci 11, 1839-1842.
37. Muthukumaraswamy, S.D., and Johnson, B.W. (2004). Primary motor cortex activation
during action observation revealed by wavelet analysis of the EEG. Clin Neurophysiol
115, 1760-1766.
38. Muthukumaraswamy, S.D., and Johnson, B.W. (2004). Changes in rolandic mu rhythm
during observation of a precision grip. Psychophysiology 41, 152-156.
31
39. Muthukumaraswamy, S.D., Johnson, B.W., and McNair, N.A. (2004). Mu rhythm
modulation during observation of an object-directed grasp. Brain Res Cogn Brain Res
19, 195-201.
40. Arnstein, D., Cui, F., Keysers, C., Maurits, N.M., and Gazzola, V. (2011). mu-
suppression during action observation and execution correlates with BOLD in dorsal
premotor, inferior parietal, and SI cortices. J Neurosci 31, 14243-14249.
41. Mukamel, R., Ekstrom, A.D., Kaplan, J., Iacoboni, M., and Fried, I. (2010). Single-
neuron responses in humans during execution and observation of actions. Curr Biol 20,
750-756.
42. Pazzaglia, M., Smania, N., Corato, E., and Aglioti, S.M. (2008). Neural underpinnings
of gesture discrimination in patients with limb apraxia. J Neurosci 28, 3030-3041.
43. Pazzaglia, M., Pizzamiglio, L., Pes, E., and Aglioti, S.M. (2008). The sound of actions
in apraxia. Curr Biol 18, 1766-1772.
44. van der Gaag, C., Minderaa, R.B., and Keysers, C. (2007). Facial expressions: what the
mirror neuron system can and cannot tell us. Soc Neurosci 2, 179-222.
45. Adolphs, R., Damasio, H., Tranel, D., Cooper, G., and Damasio, A.R. (2000). A role
for somatosensory cortices in the visual recognition of emotion as revealed by three-
dimensional lesion mapping. J Neurosci 20, 2683-2690.
46. Kaas, J.H. (2004). Somatosensory System. In The Human Nervous System. 2nd ed., G.
Paxinos and J.K. Mai, eds. (London: Elsevier), pp. 1059-1092.
47. Craig, A.D. (2006). Retrograde analyses of spinothalamic projections in the macaque
monkey: input to ventral posterior nuclei. J Comp Neurol 499, 965-978.
48. Pons, T.P., and Kaas, J.H. (1986). Corticocortical connections of area 2 of
somatosensory cortex in macaque monkeys: a correlative anatomical and
electrophysiological study. J Comp Neurol 248, 313-335.
32
49. Lederman, S.J., and Klatzky, R.L. (2009). Haptic perception: a tutorial. Atten Percept
Psychophys 71, 1439-1459.
50. Maunsell, J.H., and van Essen, D.C. (1983). The connections of the middle temporal
visual area (MT) and their relationship to a cortical hierarchy in the macaque monkey. J
Neurosci 3, 2563-2586.
51. Lewis, J.W., and Van Essen, D.C. (2000). Corticocortical connections of visual,
sensorimotor, and multimodal processing areas in the parietal lobe of the macaque
monkey. J Comp Neurol 428, 112-137.
52. Rozzi, S., Calzavara, R., Belmalih, A., Borra, E., Gregoriou, G.G., Matelli, M., and
Luppino, G. (2006). Cortical connections of the inferior parietal cortical convexity of
the macaque monkey. Cereb Cortex 16, 1389-1417.
53. Ishida, H., Nakajima, K., Inase, M., and Murata, A. (2009). Shared Mapping of Own
and Others' Bodies in Visuotactile Bimodal Area of Monkey Parietal Cortex. J Cogn
Neurosci.
54. Keysers, C., and Perrett, D.I. (2004). Demystifying social cognition: a Hebbian
perspective. Trends Cogn Sci 8, 501-507.
55. Disbrow, E., Litinas, E., Recanzone, G.H., Slutsky, D.A., and Krubitzer, L.A. (2002).
Thalamocortical connections of the parietal ventral area (PV) and the second
somatosensory area (S2) in macaque monkeys. Thalamus and Related Systems 1, 289-
302.
56. Eickhoff, S.B., Grefkes, C., Zilles, K., and Fink, G.R. (2007). The somatotopic
organization of cytoarchitectonic areas on the human parietal operculum. Cereb Cortex
17, 1800-1811.
33
57. Disbrow, E., Litinas, E., Recanzone, G.H., Padberg, J., and Krubitzer, L. (2003).
Cortical connections of the second somatosensory area and the parietal ventral area in
macaque monkeys. J Comp Neurol 462, 382-399.
58. Hackett, T.A. (2007). Organization and correspondence of the auditory cortex of
humans and nonhuman primates. In Evolution of Nervous Systems, J.H. Kaas, ed.
(Oxford: Elsevier), pp. 109-119.
59. Mufson, E.J., and Mesulam, M.M. (1982). Insula of the old world monkey. II: Afferent
cortical input and comments on the claustrum. J Comp Neurol 212, 23-37.
60. Brooks, J., and Tracey, I. (2005). From nociception to pain perception: imaging the
spinal and supraspinal pathways. J Anat 207, 19-33.
61. Craig, A.D., and Zhang, E.T. (2006). Retrograde analyses of spinothalamic projections
in the macaque monkey: input to posterolateral thalamus. J Comp Neurol 499, 953-964.
62. Bjornsdotter, M., Loken, L., Olausson, H., Vallbo, A., and Wessberg, J. (2009).
Somatotopic organization of gentle touch processing in the posterior insular cortex. J
Neurosci 29, 9314-9320.
63. Augustine, J.R. (1996). Circuitry and functional aspects of the insular lobe in primates
including humans. Brain Res Brain Res Rev 22, 229-244.
64. Keysers, C., Wicker, B., Gazzola, V., Anton, J.L., Fogassi, L., and Gallese, V. (2004).
A touching sight: SII/PV activation during the observation and experience of touch.
Neuron 42, 335-346.
65. Ebisch, S.J., Perrucci, M.G., Ferretti, A., Del Gratta, C., Romani, G.L., and Gallese, V.
(2008). The sense of touch: embodied simulation in a visuotactile mirroring mechanism
for observed animate or inanimate touch. J Cogn Neurosci 20, 1611-1623.
34
66. Schaefer, M., Xu, B., Flor, H., and Cohen, L.G. (2009). Effects of different viewing
perspectives on somatosensory activations during observation of touch. Hum Brain
Mapp 30, 2722-2730.
67. Blakemore, S.J., Bristow, D., Bird, G., Frith, C., and Ward, J. (2005). Somatosensory
activations during the observation of touch and a case of vision-touch synaesthesia.
Brain 128, 1571-1583.
68. Krubitzer, L., Clarey, J., Tweedale, R., Elston, G., and Calford, M. (1995). A
redefinition of somatosensory areas in the lateral sulcus of macaque monkeys. J
Neurosci 15, 3821-3839.
69. Arnow, B.A., Millheiser, L., Garrett, A., Lake Polan, M., Glover, G.H., Hill, K.R.,
Lightbody, A., Watson, C., Banner, L., Smart, T., et al. (2009). Women with
hypoactive sexual desire disorder compared to normal females: a functional magnetic
resonance imaging study. Neuroscience 158, 484-502.
70. Ferretti, A., Caulo, M., Del Gratta, C., Di Matteo, R., Merla, A., Montorsi, F., Pizzella,
V., Pompa, P., Rigatti, P., Rossini, P.M., et al. (2005). Dynamics of male sexual
arousal: distinct components of brain activation revealed by fMRI. Neuroimage 26,
1086-1096.
71. Hamann, S., Herman, R.A., Nolan, C.L., and Wallen, K. (2004). Men and women differ
in amygdala response to visual sexual stimuli. Nat Neurosci 7, 411-416.
72. Bufalari, I., Aprile, T., Avenanti, A., Di Russo, F., and Aglioti, S.M. (2007). Empathy
for pain and touch in the human somatosensory cortex. Cereb Cortex 17, 2553-2561.
73. Banissy, M.J., Kadosh, R.C., Maus, G.W., Walsh, V., and Ward, J. (2009). Prevalence,
characteristics and a neurocognitive model of mirror-touch synaesthesia. Exp Brain
Res.
35
74. Banissy, M.J., and Ward, J. (2007). Mirror-touch synesthesia is linked with empathy.
Nat Neurosci 10, 815-816.
75. Freund, H.J. (2003). Somatosensory and motor disturbances in patients with parietal
lobe lesions. Adv Neurol 93, 179-193.
76. Caggiano, V., Fogassi, L., Rizzolatti, G., Thier, P., and Casile, A. (2009). Mirror
neurons differentially encode the peripersonal and extrapersonal space of monkeys.
Science 324, 403-406.
77. Umilta, M.A., Kohler, E., Gallese, V., Fogassi, L., Fadiga, L., Keysers, C., and
Rizzolatti, G. (2001). I know what you are doing. a neurophysiological study. Neuron
31, 155-165.
78. Fabbri-Destro, M., and Rizzolatti, G. (2008). Mirror neurons and mirror systems in
monkeys and humans. Physiology (Bethesda) 23, 171-179.
79. Iacoboni, M., and Dapretto, M. (2006). The mirror neuron system and the consequences
of its dysfunction. Nat Rev Neurosci 7, 942-951.
80. Rizzolatti, G., and Craighero, L. (2004). The mirror-neuron system. Annu Rev
Neurosci 27, 169-192.
81. Rizzolatti, G., and Fabbri-Destro, M. (2008). The mirror system and its role in social
cognition. Curr Opin Neurobiol 18, 179-184.
82. Rizzolatti, G., Ferrari, P.F., Rozzi, S., and Fogassi, L. (2006). The inferior parietal
lobule: where action becomes perception. Novartis Found Symp 270, 129-140;
discussion 140-125, 164-129.
83. Rizzolatti, G., and Sinigaglia, C. (2007). Mirror neurons and motor intentionality. Funct
Neurol 22, 205-210.
84. Etzel, J.A., Gazzola, V., and Keysers, C. (2009). An introduction to anatomical ROI-
based fMRI classification analysis. Brain Res 1282, 114-125.
36
85. Rizzolatti, G., Camarda, R., Fogassi, L., Gentilucci, M., Luppino, G., and Matelli, M.
(1988). Functional organization of inferior area 6 in the macaque monkey. II. Area F5
and the control of distal movements. Exp Brain Res 71, 491-507.
86. Keysers, C., Kaas, J.H., and Gazzola, V. (2010). Somatosensation in social perception.
Nat Rev Neurosci 11, 417-428.
87. Gazzola, V., Aziz-Zadeh, L., and Keysers, C. (2006). Empathy and the somatotopic
auditory mirror system in humans. Curr Biol 16, 1824-1829.
88. Ricciardi, E., Bonino, D., Sani, L., Vecchi, T., Guazzelli, M., Haxby, J.V., Fadiga, L.,
and Pietrini, P. (2009). Do We Really Need Vision? How Blind People "See" the
Actions of Others. Journal of Neuroscience 29, 9719-9724.
89. Costantini, M., Galati, G., Ferretti, A., Caulo, M., Tartaro, A., Romani, G.L., and
Aglioti, S.M. (2005). Neural systems underlying observation of humanly impossible
movements: an FMRI study. Cereb Cortex 15, 1761-1767.
90. Buccino, G., Binkofski, F., Fink, G.R., Fadiga, L., Fogassi, L., Gallese, V., Seitz, R.J.,
Zilles, K., Rizzolatti, G., and Freund, H.J. (2001). Action observation activates
premotor and parietal areas in a somatotopic manner: an fMRI study. Eur J Neurosci
13, 400-404.
91. Pierno, A.C., Tubaldi, F., Turella, L., Grossi, P., Barachino, L., Gallo, P., and Castiello,
U. (2009). Neurofunctional modulation of brain regions by the observation of pointing
and grasping actions. Cereb Cortex 19, 367-374.
92. Molnar-Szakacs, I., Kaplan, J., Greenfield, P.M., and Iacoboni, M. (2006). Observing
complex action sequences: The role of the fronto-parietal mirror neuron system.
Neuroimage 33, 923-935.
93. Etzel, J.A., Gazzola, V., and Keysers, C. (2008). Testing simulation theory with cross-
modal multivariate classification of fMRI data. PLoS ONE 3, e3690.
37
94. Meyer, K., Kaplan, J.T., Essex, R., Damasio, H., and Damasio, A. (2011). Seeing touch
is correlated with content-specific activity in primary somatosensory cortex. Cereb
Cortex 21, 2113-2121.
95. Flanagan, J.R., Vetter, P., Johansson, R.S., and Wolpert, D.M. (2003). Prediction
precedes control in motor learning. Curr Biol 13, 146-150.
96. Miall, R.C., and Wolpert, D.M. (1996). Forward models for physiological motor
control. Neural Netw. 9, 1265-1279.
97. Hennenlotter, A., Schroeder, U., Erhard, P., Castrop, F., Haslinger, B., Stoecker, D.,
Lange, K.W., and Ceballos-Baumann, A.O. (2005). A common neural basis for
receptive and expressive communication of pleasant facial affect. Neuroimage 26, 581-
591.
98. van der Gaag, C., Minderaa, R., and Keysers, C. (2007). Facial expressions: what the
mirror neuron system can and cannot tell us. Social Neuroscience 2, 179-222.
99. Leslie, K.R., Johnson-Frey, S.H., and Grafton, S.T. (2004). Functional imaging of face
and hand imitation: towards a motor theory of empathy. Neuroimage 21, 601-607.
100. Pitcher, D., Garrido, L., Walsh, V., and Duchaine, B.C. (2008). Transcranial magnetic
stimulation disrupts the perception and embodiment of facial expressions. J Neurosci
28, 8929-8933.
101. Osborn, J., and Derbyshire, S.W. Pain sensation evoked by observing injury in others.
Pain 148, 268-274.
102. Singer, T., Seymour, B., O'Doherty, J., Kaube, H., Dolan, R.J., and Frith, C.D. (2004).
Empathy for pain involves the affective but not sensory components of pain. Science
303, 1157-1162.
38
103. Singer, T., Seymour, B., O'Doherty, J.P., Stephan, K.E., Dolan, R.J., and Frith, C.D.
(2006). Empathic neural responses are modulated by the perceived fairness of others.
Nature 439, 466-469.
104. Botvinick, M., Jha, A.P., Bylsma, L.M., Fabian, S.A., Solomon, P.E., and Prkachin,
K.M. (2005). Viewing facial expressions of pain engages cortical areas involved in the
direct experience of pain. Neuroimage 25, 312-319.
105. Decety, J., Echols, S., and Correll, J. (2009). The Blame Game: The Effect of
Responsibility and Social Stigma on Empathy for Pain. J Cogn Neurosci.
106. Lamm, C., Batson, C.D., and Decety, J. (2007). The neural substrate of human
empathy: effects of perspective-taking and cognitive appraisal. J Cogn Neurosci 19, 42-
58.
107. Saarela, M.V., Hlushchuk, Y., Williams, A.C., Schurmann, M., Kalso, E., and Hari, R.
(2007). The compassionate brain: humans detect intensity of pain from another's face.
Cereb Cortex 17, 230-237.
108. Jackson, P.L., Meltzoff, A.N., and Decety, J. (2005). How do we perceive the pain of
others? A window into the neural processes involved in empathy. Neuroimage 24, 771-
779.
109. Jackson, P.L., Brunet, E., Meltzoff, A.N., and Decety, J. (2006). Empathy examined
through the neural mechanisms involved in imagining how I feel versus how you feel
pain. Neuropsychologia 44, 752-761.
110. Costantini, M., Galati, G., Romani, G.L., and Aglioti, S.M. (2008). Empathic neural
reactivity to noxious stimuli delivered to body parts and non-corporeal objects. Eur J
Neurosci 28, 1222-1230.
111. Lamm, C., and Decety, J. (2008). Is the extrastriate body area (EBA) sensitive to the
perception of pain in others? Cereb Cortex 18, 2369-2373.
39
112. Lamm, C., Meltzoff, A.N., and Decety, J. (2009). How Do We Empathize with
Someone Who Is Not Like Us? A Functional Magnetic Resonance Imaging Study. J
Cogn Neurosci.
113. Lamm, C., Nusbaum, H.C., Meltzoff, A.N., and Decety, J. (2007). What are you
feeling? Using functional magnetic resonance imaging to assess the modulation of
sensory and affective responses during empathy for pain. PLoS ONE 2, e1292.
114. Morrison, I., and Downing, P.E. (2007). Organization of felt and seen pain responses in
anterior cingulate cortex. Neuroimage 37, 642-651.
115. Morrison, I., Lloyd, D., di Pellegrino, G., and Roberts, N. (2004). Vicarious responses
to pain in anterior cingulate cortex: is empathy a multisensory issue? Cognitive,
affective & behavioral neuroscience 4, 270-278.
116. Jabbi, M., Swart, M., and Keysers, C. (2007). Empathy for positive and negative
emotions in the gustatory cortex. Neuroimage 34, 1744-1753.
117. Wicker, B., Keysers, C., Plailly, J., Royet, J.P., Gallese, V., and Rizzolatti, G. (2003).
Both of us disgusted in My insula: the common neural basis of seeing and feeling
disgust. Neuron 40, 655-664.
118. Carr, L., Iacoboni, M., Dubeau, M.C., Mazziotta, J.C., and Lenzi, G.L. (2003). Neural
mechanisms of empathy in humans: a relay from neural systems for imitation to limbic
areas. Proc Natl Acad Sci U S A 100, 5497-5502.
119. Lamm, C., Decety, J., and Singer, T. (2011). Meta-analytic evidence for common and
distinct neural networks associated with directly experienced pain and empathy for
pain. Neuroimage 54, 2492-2502.
120. Church, R.M. (1959). Emotional reactions of rats to the pain of others. J. Comp.
Physiol. Psychol. 52, 132-134.
40
121. Atsak, P., Orre, M., Bakker, P., Cerliani, L., Roozendaal, B., Gazzola, V., Moita, M.,
and Keysers, C. (2011). Experience modulates vicarious freezing in rats: a model for
empathy. PLoS One 6, e21855.
122. Rice, G.E., and Gainer, P. (1962). "Altruism" in the albino rat. J Comp Physiol Psychol
55, 123-125.
123. Jabbi, M., and Keysers, C. (2008). Inferior frontal gyrus activity triggers anterior insula
response to emotional facial expressions. Emotion 8, 775-780.
124. Zaki, J., Ochsner, K.N., Hanelin, J., Wager, T.D., and Mackey, S.C. (2007). Different
circuits for different pain: patterns of functional connectivity reveal distinct networks
for processing pain in self and others. Soc Neurosci 2, 276-291.
125. Jabbi, M., Bastiaansen, J., and Keysers, C. (2008). A common anterior insula
representation of disgust observation, experience and imagination shows divergent
functional connectivity pathways. PLoS ONE 3, e2939.
126. Adolphs, R., Tranel, D., and Damasio, A.R. (2003). Dissociable neural systems for
recognizing emotions. Brain Cogn 52, 61-69.
127. Calder, A.J., Keane, J., Manes, F., Antoun, N., and Young, A.W. (2000). Impaired
recognition and experience of disgust following brain injury. Nat Neurosci 3, 1077-
1078.
128. Avenanti, A., Sirigu, A., and Aglioti, S.M. (2010). Racial bias reduces empathic
sensorimotor resonance with other-race pain. Curr Biol 20, 1018-1022.
129. Hein, G., Silani, G., Preuschoff, K., Batson, C.D., and Singer, T. (2010). Neural
responses to ingroup and outgroup members' suffering predict individual differences in
costly helping. Neuron 68, 149-160.
41
130. Gazzola, V., Rizzolatti, G., Wicker, B., and Keysers, C. (2007). The anthropomorphic
brain: the mirror neuron system responds to human and robotic actions. Neuroimage
35, 1674-1684.
131. Gazzola, V., van der Worp, H., Mulder, T., Wicker, B., Rizzolatti, G., and Keysers, C.
(2007). Aplasics born without hands mirror the goal of hand actions with their feet.
Curr Biol 17, 1235-1240.
132. Keysers, C. (2011). The Empathic Brain.
133. Schippers, M.B., and Keysers, C. (2011). Mapping the flow of information within the
putative mirror neuron system during gesture observation. Neuroimage 57, 37-44.
134. Heyes, C. (2001). Causes and consequences of imitation. Trends Cogn Sci (Regul Ed)
5, 253-261.
135. Brass, M., and Heyes, C. (2005). Imitation: is cognitive neuroscience solving the
correspondence problem? Trends Cogn Sci (Regul Ed) 9, 489-495.
136. Del Giudice, M., Manera, V., and Keysers, C. (2009). Programmed to learn? The
ontogeny of mirror neurons. Dev Sci 12, 350-363.
137. Del Giudice, M., Manera, V., and Keysers, C. (2009). Programmed to learn? The
ontogeny of mirror neurons. Developmental Sci 12, 350-363.
138. Oztop, E., and Arbib, M.A. (2002). Schema design and implementation of the grasp-
related mirror neuron system. Biological Cybernetics 87, 116-140.
139. Shmuelof, L., and Zohary, E. (2005). Dissociation between ventral and dorsal fMRI
activation during object and action recognition. Neuron 47, 457-470.
140. de Lange, F.P., Spronk, M., Willems, R.M., Toni, I., and Bekkering, H. (2008).
Complementary systems for understanding action intentions. Curr Biol 18, 454-457.
141. Keysers, C., and Gazzola, V. (2007). Integrating simulation and theory of mind: from
self to social cognition. Trends Cogn Sci 11, 194-196.
42
142. Kokal, I., Gazzola, V., and Keysers, C. (2009). Acting Together in and beyond the
Mirror Neuron System. Neuroimage.
143. Hein, G., and Singer, T. (2008). I feel how you feel but not always: the empathic brain
and its modulation. Curr Opin Neurobiol 18, 153-158.
43
Figure 1: Brain regions in which mirror neurons have been recorded from in the macaque
monkey[1, 4-7, 9] (left) and regions showing vicarious motor activations in human fMRI[15,
16] (right), both rendered on partially inflated lateral surface reconstructions of the cortex.
Note that this lateral view hides vicarious motor activations in the cerebellum and the medial
SMA. Questions marks on the left remind us of how many brain regions have not yet been
systematically explored for mirror neurons in monkeys.
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