1

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

2

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

3

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

4

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

5

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

6

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

7

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

8

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

9

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

10

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-

11

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

12

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

13

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

14

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

15

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

16

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

17

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.