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Journal of Physiology - Paris 99 (2006) 396–405 www.elsevier.com/locate/jphysparis The role of ventral premotor cortex in action execution and action understanding Ferdinand Binkofski a a,* , Giovanni Buccino b Department of Neurology and Neuroimage Nord, University Hospital Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Lübeck, Germany b Dipartimento di Neuroscienze, Sezione di Fisiologia, Universita’ di Parma, Italy Abstract The human ventral premotor cortex overlaps, at least in part, with Broca’s region in the dominant cerebral hemisphere, that is known to mediate the production of language and contributes to language comprehension. This region is constituted of Brodmann’s areas 44 and 45 in the inferior frontal gyrus. We summarize the evidence that the motor related part of Broca’s region is localized in the opercular portion of the inferior frontal cortex, mainly in area 44 of Brodmann. According to our own data, there seems to be a homology between Brodmann area 44 in humans and the monkey area F5. The non-language related motor functions of Broca’s region comprise complex hand movements, associative sensorimotor learning and sensorimotor integration. Brodmann’s area 44 is also a part of a specialized parieto-premotor network and interacts significantly with the neighbouring premotor areas. In the ventral premotor area F5 of monkeys, the so called mirror neurons have been found which discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding not only to the observation of mouth actions, but also to sounds characteristic to actions have been found. In humans, through an fMRI study, it has been shown that the observation of actions performed with the hand, the mouth and the foot leads to the activation of different sectors of Broca’s area and premotor cortex, according to the effector involved in the observed action, following a somatotopic pattern which resembles the classical motor cortex homunculus. On the other hand the evidence is growing that human ventral premotor cortex, especially Brodmann’s area 44, is involved in polymodal action processing. These results strongly support the existence of an execution–observation matching system (mirror neuron system). It has been proposed that this system is involved in polymodal action recognition and might represent a precursor of language processing. Experimental evidence in favour of this hypothesis both in the monkey and humans is shortly reviewed. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Broca’s region; Ventral premotor cortex; Mirror neuron system; Action recognition; Motor resonance; Language processing 1. Introduction This review consists of two parts. In the first part the data coming from neurophysiological and brain imaging studies concerning the role of ventral premotor cortex in action execution both in monkeys and humans will be * Corresponding author. Address: Department of Neurology, University Hospital Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. Tel.: +49 451 500 2499; fax: +49 451 500 2489. E-mail address: [email protected] (F. Binkofski). 0928-4257/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2006.03.005 reviewed. In the second part, the features of a particular set of neurons, the so called mirror neurons, first described in area F5 will be discussed. A major problem when considering the role of ventral premotor cortex in action execution is the difficulty to compare monkey data with human data: in fact, classically the ventral premotor cortex of the monkey (area F5) is thought to be endowed with a motor representation of hand and mouth goal-directed actions, while the same sector in humans (Broca’s area) is thought to be devoted to speech production. Recent brain imaging studies have clearly shown a motor representation of hand actions also in Broca’s area, thus supporting the F. Binkofski, G. Buccino / Journal of Physiology - Paris 99 (2006) 396–405 notion of a homology between area F5 in the monkey and Broca’s area in humans. Mirror neurons discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding to the observation of mouth actions have also been found. In humans, by means of an fMRI study, it has been shown that the observation of actions performed with the hand, the mouth and the foot leads to the activation of different sectors of Broca’s area and premotor cortex, according to the effector involved in the observed action. These activations follow a somatotopic pattern which resembles the classical motor cortex homunculus. These results strongly support the existence of an observation–execution matching system in humans (mirror neuron system), similar to that found in the monkey. Whereas in monkeys mirror neurons responding to action related sounds have been discovered, the evidence is growing that in humans mirror neurons not only code action words, but also contributes to process action related sentences and this in a somatotopic manner. Thus, there is evidence that the mirror neuron system plays a fundamental role in action understanding both in humans and monkeys and might constitute a bridge between action and language processing. 2. The role of ventral premotor cortex in action execution 2.1. Motor functions of ventral premotor cortex (area F5) in the monkey Based on cytoarchitectural and histochemical data, a modern parcellation of the agranular frontal cortex has 397 been worked out in the macaque monkey (Matelli et al., 1985, 1991). Fig. 1 shows this parcellation. In the terminology proposed by Matelli and co-workers, area F1 corresponds basically to Brodmann’s area 4 (primary motor cortex), the other areas are mainly subdivisions of Brodmann’s area 6. Areas F2 and F7, which lie in the superior part of area 6, are referred to collectively as ‘‘dorsal premotor cortex’’, while areas F4 and F5, which lie in the inferior area 6, are often referred to as ‘‘ventral premotor cortex’’ (Matelli and Luppino, 2000). Neurophysiological studies showed that in area F5, which occupies the most rostral part of ventral premotor cortex in the macaque monkey, there is a motor representation of distal hand movements (Rizzolatti et al., 1981, 1988; Kurata and Tanji, 1986; Hepp-Reymond et al., 1994). The neurons of this area discharge during specific goal-directed hand movements such as grasping, holding and tearing. It has been proposed, that area F5 contains a ‘‘motor vocabulary’’ for hand actions (Rizzolatti et al., 1988; Murata et al., 1997). This area is directly connected with the primary motor cortex (F1) and receives rich input from the second somatosensory area (SII), from parietal area PF (7b), and from a parietal area located inside the intraparietal sulcus, the anterior intraparietal area (AIP) (Matsumura and Kubota, 1979; Muakkassa and Strick, 1979; Godschalk et al., 1984; Matelli et al., 1986; Luppino et al., 1999). The study of AIP showed that many of its neurons discharge during finger and hand movements, others respond to specific visual 3-D stimuli and, finally, others discharge both during active finger movements and in response to 3-D stimuli congruent in size and shape with the coded grasping movement (Taira et al., 1990; Sakata et al., 1995). Taken together, these data suggest that the Fig. 1. Schematic drawing of the parcellation of the ventral premotor cortex in monkeys (modified after Matelli and Luppino, 1996, with permission). Lateral view of the monkey brain showing the cytoarchitectonic parcellation of the motor cortex and the posterior parietal cortex (area VIP, buried inside IP, is not shown). The motor area F7, receiving its main input from the prefrontal lobe, is indicated in blue. Areas F2 and F7 are often referred to as dPM; areas F4 and F5 form the vPM. AI, inferior arcuate sulcus; AS, superior arcuate sulcus; C, central sulcus; DLPFd, dorsolateral prefrontal cortex dorsal part; DLPFv, dorsolateral prefrontal cortex ventral part; IP, intraparietal sulcus; L, lateral fissure; Lu, lunate sulcus; P, principal sulcus; SI, primary somatosensory cortex; ST, superior temporal sulcus. 398 F. Binkofski, G. Buccino / Journal of Physiology - Paris 99 (2006) 396–405 circuit connecting AIP and F5 plays a pivotal role in controlling the organization of hand/object interactions (Jeannerod et al., 1995). 2.2. Area F5 in the monkey and Broca’s region in humans In humans the ventral sector of the premotor cortex is formed by two areas: the ventral part of area 6a alpha and BA 44 (Vogt and Vogt, 1919). Brodmann’s areas 44 and 45, occupying the opercular and triangular parts of the inferior frontal gyrus, form the Broca’s region (Broca, 1864; Amunts et al., 1999). Brodmann’s areas 44 and 6 share a common basic cytoarchitectonic structure, the main characteristics of which are the poverty (BA 44) or lack (BA 6) of granular cells (see Campbell, 1905; von Economo, 1929) and the presence of large pyramid cells in the third layer. Classically, both ventral BA 6 and BA 44 were thought of as areas controlling oro-laryngeal movements, but with a different specialization and selectivity. The most lateral part of BA 6 was considered to be responsible for the motor control of oro-laryngeal movements, regardless of the movement purpose, while, in contrast, BA 44 was considered to be the main speech motor area. Because Broca’s region occurred only in the evolution of the human brain, the search for homologies between Broca’s region and ventral premotor areas of non-human primates is somehow difficult. It is interesting to note, however, that a homology between BA 44 and area F5 was already suggested by von Bonin and Bailey (1947) on the basis of their cytoarchitectonic studies. (In their terminology, F5 was called FCBm.) This view has been recently fully supported by Petrides and Pandya (1994); (see also Galaburda and Pandya, 1982; Preuss et al., 1996). A possible weakness of this homology (see Passingham, 1993) is the richness of the oro-laryngeal representation, including that of speech control, in human Broca’s area and, on the contrary, the presence of a motor representation of hand actions in monkey area F5. A series of recent neuroimaging studies, which will be shortly reviewed in this article, has clearly demonstrated that the role of Broca’s area 44 is not restricted to speech production and that in this area there is not only an oro-laryngeal motor representation, but also a motor representation of distal hand movements. Obviously, the relative cortical space for the two representations is not the same. However, the development of the cortex devoted to oro-laryngeal representations specifically in BA 44 is probably not a mere coincidence, but is due to the close evolutionary relation between action and speech (see Rizzolatti and Arbib, 1998). that are different from speech. Activation of the right inferior frontal cortex was found during overt and covert production of gestures (Bonda et al., 1995; Parsons et al., 1995; Decety et al., 1994), especially during mental rotations necessary for hand recognition (Parsons et al., 1995), during mental imagery of grasping movements (Decety et al., 1994; Grafton et al., 1996a,b), during preparation of finger movements on the basis of a copied movement (Krams et al., 1998), during imagery and performance of visually guided movements (Binkofski et al., 2000; Toni et al., 2001). The vPMC was also found to be of importance for motor tasks with high motor execution demands (Winstein et al., 1997). Ventral premotor cortex seems to play a crucial role in motor imagery as repeatedly shown in neuroimaging studies (Decety et al., 1994; Stephan et al., 1995; Binkofski et al., 2000). Common to all these tasks was the performance of complex motor acts with higher degree of sensorimotor control. The frontal opercular cortex of the right hemisphere was also shown to be critically involved in the learning of explicit and implicit motor sequences (Seitz and Roland, 1992; Rauch et al., 1995; Hazeltine et al., 1997). The frontal opercular region seems also to be involved in the initial learning of novel, arbitrary visuo-motor associations (Toni et al., 2001), while overlearned performance is likely to rely on dorsal premotor cortex (Toni et al., 2001, 2002). The specific role of area 44 in the execution of goal directed hand actions could also be demonstrated in another experiment in which volunteers were asked to manipulate complex objects, as compared to the manipulation of a sphere (Binkofski et al., 1999). The experiment consisted of two conditions: in one condition the participants were asked to merely manipulate complex objects and avoid covert naming of them, in the other condition the participants were explicitly asked to covertly name the explored objects. In the contrast between both conditions containing manipulation of complex objects and manipulation of a sphere ventral premotor activations were found. The comparison of the coordinates of the activated foci located around the opercular and triangular parts of the inferior frontal gyrus with the coordinates of the probability maps of BAs 44 and 45 (Amunts et al., 1999) demonstrated that the activation foci located in the pars triangularis related to covert naming of objects fitted entirely into BA 45. The foci activated during complex object manipulation without naming and located in vPMC fitted into the borders of BA 44. These results underline the notion that within Broca’s region the area 44 is relevant for both grasping and manipulation. 2.3. Involvement of human ventral premotor cortex in processing complex actions: evidence from neuroimaging 2.4. Combination of cytoarchitectonic and imaging data for identification of similarities between human area 44 and monkey area F5 New neuroimaging techniques helped to extend our understanding of functions of the frontal opercular cortex While investigating motor imagery under different conditions we found that the posterior, opercular part of the F. Binkofski, G. Buccino / Journal of Physiology - Paris 99 (2006) 396–405 human inferior frontal cortex became specifically engaged during imagery of abstract movements (Binkofski et al., 2000). This imagery of abstract movements was referred to conditions in which movement had to be imagined from a third person’s perspective. The imagery of one’s own movement was associated with activation of the left ventral opercular cortex, while the imagery of a moving target caused activation of the right ventral opercular cortex. After transformation of our data into the standardized reference brain atlas by Roland and Zilles (1994), we superimposed our activation data onto the cytoarchitectonic data of the Brodmann areas 44 and 45 (Amunts et al., 1999). The superimposition of our activation data with the probabilistic maps of areas 44 and 45 obtained from cytoarchitectonic data of 10 individual brains allows for exact localization of the activation foci within one of these areas. Here, we could clearly demonstrate that during imagery of one’s own limb motion, from an observer’s perspective, there was left-hemispheric activation of area 44, whereas during imagery of spatial target motion in extrapersonal space, significant activation of the right area 44 became apparent (Fig. 2). Moreover, we showed that the centre of gravity of area 44 was significantly caudal to area 45 and rostral to lower area 6 of premotor cortex. These data support the view that the left-hemispheric activation of Broca’s region reflected ‘‘pragmatic’’ motor processing, while the right-hemispheric activation of Broca’s homologue was related to explicit motor processing of motion. Interestingly, in our study the inferior frontal cortex was not activated by imagery of simple finger movements but of more advanced concepts of motion. Imagery of visually guided finger movements was associated with activation of more dorsal parts of lateral premotor cortex, possibly in the homologue to monkey area F4. We suggest that these frontal opercular activations in humans within the cytoarchitectonical borders of Brodmann’s area 44 may correspond to neuronal activations related to action perception and recognition as reported 399 for a set of neurones in the ventral premotor cortex in the area F5 of macaques (Rizzolatti et al., 1996a; Gallese et al., 1996). This notion is strongly supported in a review by Rizzolatti et al. (2002). 3. The mirror neuron system 3.1. The mirror neuron system in the monkey Neurophysiological studies have shown that a set of F5 neurons discharges both when the monkey performs specific goal-directed hand actions and when it observes another monkey or an experimenter performing the same or a similar action (Gallese et al., 1996; Rizzolatti et al., 1996a). These neurons are called mirror neurons. The congruence between the action coded by the neuron in motor terms and that triggering the same neuron visually may be very strict: in this case only the observation of an action identical to that coded motorically by the neuron can activate it. More often, this congruence is only broad; in this case, the observed and the executed action coded by the neuron share the goal of the action itself rather than the single movements constituting it. During action observation mirror neurons discharge only when a biological effector (a hand, for example) interacts with an object; if the action is executed with a tool the neuron is not active. Also mirror neurons are not active when the observed action is simply mimicked, that is not acted upon an object. Finally, mirror neurons do not discharge during the mere visual presentation of an object. Fig. 3 shows some examples of mirror neurons. The visual properties of mirror neurons resemble those of neurons found by Perrett et al. (1989) in the superior temporal sulcus region. These neurons, like mirror neurons, respond to the presentation of goal-directed hand actions, but also to walking, turning the head, moving the hand and bending the torso (for a review see Carey et al., 1997). Differently from mirror neurons described in area F5, neurons of STS region do not seem to have a motor counterpart. Fig. 2. Activation of the left area 44 during processing of internal motion (A) and of the right area 44 during processing of external motion (B). Superposition of activation foci (blue, from Binkofski et al., 2000) on the probablilistic cytoarchitectonic map of area 44. 400 F. Binkofski, G. Buccino / Journal of Physiology - Paris 99 (2006) 396–405 Fig. 3. Characteristic properties of mirror neurons. (a) Strong activation of a mirror neuron in the macaque ventral premotor area F5 during execution of a grasping movement by the macaque (right) and during the observation of a similar grasping movement performed by an experimenter (left). (b) During observation of a grasping movement performed with a tool remains the mirror neuron silent. Adapted from Gallese et al., 1996. Since their discovery, the hypothesis has been forwarded that mirror neurons may play an important role both in action recognition and in motor learning (Jeannerod, 1994). Evidence in favour of the fundamental role of mirror neurons in action understanding has been provided by an electrophysiological study (Umilta et al., 2001). In the experiment, two conditions were considered: in the first one (vision condition) the animal could see the whole sequence of a hand goal-directed action, in the second one (hidden condition) the final part of the action was hidden from the sight of the monkey by means of a screen. In this last condition, however, the animal was shown that an object, for example a piece of food, was placed behind the screen which prevented the observation of the final part of the executed action. The results showed that mirror neurons discharge not only during the observation of the whole action, but also when the final part of it is hidden. As a control, a mimicked action was presented in the same conditions. As expected, in this case, the neuron did not discharge, neither in the full vision condition nor in the hidden condition. Actions may be recognized also when presented acoustically, from their typical sound. Besides visual properties, a recent experiment has demonstrated that about 15% of mirror neurons also respond to the peculiar sound of an action. These neurons are called audio–visual mirror neurons (Koehler et al., 2002). Audio–visual mirror neurons could be used to recognize actions performed by other individuals even if only heard. It has been argued that these neurons code the action content, which may be triggered either visually or acoustically, thus representing a possible, fundamental step for the evolution of language. The studies reported so far concerned mirror neurons related to hand actions. More recently it has been demonstrated that in area F5 there are also mirror neurons which discharge during the execution and observation of mouth actions. Most of mouth mirror neurons become active during the execution and observation of mouth actions related to ingestive functions such as grasping, sucking or breaking food. Some of them respond during the execution and observation of oral communicative actions such as lipsmacking (Ferrari et al., 2003). 3.2. The mirror neuron system in humans There is increasing evidence that a mirror neuron system also exists in humans. Converging data supporting this notion come from experiments carried out with neurophysiological, behavioural and brain imaging techniques. An early, indirect evidence in favour of the existence of a mirror neuron system in humans has been provided by Fadiga et al. (1995) through a transcranial magnetic stimulation (TMS). During this experiment, single pulse TMS was delivered while subjects were observing an experimenter performing various distal hand actions in front of them. As control conditions, single pulse TMS was delivered during object observation, dimming detection and observation of arm movements. Motor evoked potentials were recorded from different hand muscles. Results showed that during hand action observation, but not in the other conditions, there was an increase of the amplitude of motor evoked potentials (MEPs) recorded from those hand muscles, normally recruited when the observed action is actually performed by the observer. These results were fully confirmed by Strafella and Paus (2000). Furthermore, using the same technique, Gangitano et al. (2001) found that during hand action observation, MEPs recorded from muscles involved in the actual execution of the observed action are modulated in a fashion strictly resembling the time-course of the observed action. Taken together, these TMS data support the notion of a mirror neuron system coupling action execution and action observation in terms of both the muscles involved and the temporal sequence of the action. In keeping with these results are those obtained by Cochin et al. (1999) using quantified electroencephalogra- F. Binkofski, G. Buccino / Journal of Physiology - Paris 99 (2006) 396–405 phy (qEEG). In this study l-rhythm activity was blocked, as compared to rest, during both the observation and execution of various hand actions. Results similar to those of Cochin et al. (1999) were obtained by Hari et al. (1998) using magnetoencephalography (MEG). In this study the authors found a suppression of 15–25 Hz activity, known to originate from the precentral motor cortex, during the execution and, although to a less extent, during the observation of object manipulation. All these studies provide further evidence that observation and execution of action share common neural substrates. Evidence in favour of the existence of a mirror neuron system derives also from neuropsychological studies, using behavioural paradigms. Brass et al. (2000) investigated how the observation of movements can affect movement execution in a stimulus–response compatibility paradigm. To this purpose they contrasted the role of symbolic cues as compared to the observation of finger movements in the execution of finger movements. Subjects were faster when the relevant cue for the response was the movement as compared to the condition in which a spatial or a symbolic cue was relevant for the response. Moreover the degree of similarity between the observed and executed movement leads to a further advantage in the execution of the observed movement. These results provide a strong evidence for an influence of the observed movement on the execution of that movement. Similar results were obtained by Craighero et al. (2002) in a study in which subjects were required to prepare to grasp as fast as possible a bar oriented either clockwise or counter clockwise, after presentation of a picture showing the right hand. Two experiments were carried out: in the first experiment the picture represented the final required position for the hand to grasp the bar, as seen through a mirror. In a second experiment, in addition to stimuli used in experiment one, another two pictures were presented, obtained by rotating the hand shown in the pictures used in Experiment 1 by 90°. In both experiments, responses of the subjects were faster when the hand orientation of the picture corresponded to that achieved by the hand at the end of action, when actually executed. Moreover the responses were globally faster when the stimuli were not rotated. In the studies reported here, the observation of an action facilitates the execution of that action. These results find a clear explanation in the existence of the mirror neuron system, where by definition the visual representation of an action and its motor counterpart are anatomically and functionally embedded. All the cited studies provide little, if any, insight on the localization of mirror neuron system in humans. This issue was addressed by a number of brain imaging studies. In an early experiment devoted to identify the brain areas active during action observation, using positron emission tomography (PET), Rizzolatti et al. (1996b) found an activation of Broca’s area and of the cortex of the middle temporal gyrus and of the superior temporal sulcus region, when comparing hand action observation with the observation 401 of an object. Although Broca’s area is classically considered an area devoted to speech production, given the homology between this area and area F5 in the monkey (see above), where mirror neurons were originally discovered, this study provided evidence on the anatomical localization of the mirror neuron system in humans, at least for hand actions. A recent fMRI study showed that in humans the mirror neuron system is complex and related to different body actions performed not only with the hand, but also with the foot and the mouth. Buccino et al. (2001) asked normal volunteers to observe video sequences presenting different actions performed with the mouth, the hand and the foot, respectively. The actions shown could be either transitive (the action was acted upon an object) or intransitive (the same action previously acted upon an object, was mimicked). The following actions were presented: biting an apple, grasping a cup and a ball, kicking a ball and pushing a brake. As a control, subjects were asked to observe a static frame of each action. The observation of both transitive and intransitive actions, compared to the observation of a static frame of the same action, led to the activation of different sectors in the premotor cortex and in Broca’s area, according to the effector involved in the observed action. The different sectors largely overlapped with those where classical studies (Penfield and Rasmussen, 1950) had shown a motor representation of the different effectors. Moreover, during the observation of transitive actions, distinct sectors in the inferior parietal lobule, including areas inside the intraparietal sulcus and adjacent to it, were active, according to the effector involved in the observed action. Fig. 4 shows the results of the experiment. On the whole, this study strongly supports the claim that, as in the actual execution of actions, different, somatotopically organized frontoparietal circuits (Jeannerod et al., 1995; Rizzolatti et al., 1998) are recruited during action observation. In this context, it is worth noting that mirror neurons, similar to those described in area F5, have also been described by Fogassi et al. (1998) and Gallese et al. (2002) in the inferior parietal lobule of the monkey (area PF). The study of Buccino et al. (2001) show an involvement of the mirror neuron system during a mere observation task, thus suggesting that this system is indeed operating whatever the cognitive strategy of the observer. As previously stated, in the monkey the mirror neuron system is activated also when the animal observes a nonconspecific (an experimenter, for example) performing the same or a similar action coded by the neuron motorically. In a recent study the issue was addressed whether we recognize action performed by non-conspecifics using the same neural structures involved in the recognition of action performed by our conspecifics (Buccino et al., 2004). In an fMRI experiment normal subjects were asked to carefully observe different mouth actions performed by a man, a monkey and a dog, respectively. Two kinds of mouth actions were visually presented: biting a piece of food 402 F. Binkofski, G. Buccino / Journal of Physiology - Paris 99 (2006) 396–405 and oral communicative actions (human silent speech, monkey lip-smacking, and dog silent barking). The results showed that during the observation of biting, there is a clear activation of the pars opercularis of the inferior frontal gyrus and of the inferior parietal lobule, with no regards for the species doing the action. During the observation of oral communicative mouth actions, a different pattern of activation was observed according to the individual of the species performing the action. During the observation of silent speech there was a clear activation of Broca’s area in both hemispheres, with a marked prevalence in the left one, during the observation of lip smacking there was only a bilateral small activation in the pars opercularis of Broca’s area, with no clear asymmetry between the two hemispheres. Finally, during the observation of barking no activation was found in the Broca’s area, but activation was present only in the right superior temporal sulcus region. The results of the experiment strongly suggest that action performed by other individuals, including non-conspecifics, may be recognized in two different ways: for actions like biting or silent speech reading, there is a motor resonance of the cortical circuits involved in the actual execution of the observed actions; in other words their recognition relies on the mirror neuron system. For actions like barking this resonance is lacking. In the first case there is a ‘‘personal’’ knowledge of the action observed, in the sense that it is mapped on the observer’s motor repertoire and therefore the observer has a direct, personal experience in motor terms of it (I recognize it because I am able to do the same action I am looking at); in the second case, although still recognized as a biological action, as demonstrated by the activation of the STS region, this personal knowledge is lacking because the observer has no direct experience of the observed action in motor terms (I can approximately imitate a dog barking, but, as a matter of fact, I am not able to do it) (Buccino et al., 2004). In a recent fMRI study we looked for areas activated by recognition of tools regardless in which modality they were presented to the subjects. By using conjunction analysis between three conditions containing recognition of tools presented visually, tactically and acoustically (each contrasted with respective modality specific baseline) we found a common activation of the bilateral infero-temporal and of bilateral ventral premotor cortex (Binkofski et al., 2004). Whereas the infero-temporal activation foci represent most probably polymodal object (tool) recognition, the activation of the bilateral ventral premotor cortex is bound to polymodal coding of pragmatic properties of objects and of potential actions on them. This result indicates that polymodal mirror neurons (Koehler et al., 2002) might also exist in human ventral premotor cortex (Fig. 5). As a whole, the studies reviewed so far show an involvement of ventral premotor cortex, including the opercular part of the inferior frontal gyrus in recognizing actions. A recent topic of debate is whether, in modern humans, the mirror neuron system plays also a role in understanding actions when they are presented through language. Some experimental evidence and some theoretical approaches strongly suggest a possible link between the mirror neuron system and language (for a review see Rizzolatti and Buccino, 2005; Arbib, 2005). Given the homology between the monkey’s premotor area F5 and Broca’s region, it has been suggested that the mirror neuron system represents the neural substrate from which human language evolved (Arbib, 2005; Rizzolatti and Arbib, 1998; Rizzolatti and Buccino, 2005). Up to now only few studies have addressed the issue of a potential involvement of the motor system during processing of action related sentences. A recent fMRI study, showed that listening to sentences expressing actions performed with the mouth, the hand and the foot causes activation of different sectors of the premotor cortex, depending on the effector used in the action-related sentence (Tettamanti et al., 2005). Interestingly, these distinct sectors coincide, albeit only approximately, with those active during the observation of hand, mouth and foot actions (Buccino et al., 2001). Another recent event-related fMRI study demonstrated that, during silent reading of words referring to face, arm or leg actions, different sectors of the premotor-motor areas are active, depending on the referential meaning of the read action words (Hauk et al., 2004). The authors interpreted the results as supportive of a dynamic view according to which words are processed in neural substrates reflecting their semantics. Further, a recent combined TMS and behavioral study showed that listening to hand action related sentences, as compared to foot action related and abstract content sentences, specifically modulated the activity of the hand, as revealed by MEPs recorded from hand muscles or by responses given with the hand (Buccino et al., 2005). Taken together, the results from brain imaging studies support those theories assuming that language understanding relies on ‘‘embodiment’’. According to these theories, the understanding of action-related sentences implies an internal simulation of the actions expressed by the action-related verb, mediated by the same motor representations that are involved in their actual execution (Gallese and Lakoff, 2005). In conclusion, converging data indicate that we can recognize a large variety of actions performed by other individuals, including those belonging to other species, just matching the observed actions on our own motor system. The neural substrate of this direct matching, through which we recognize actions done by other individuals, is the mirror neuron system. This system could also mediate the processing of actions, when presented through heard and read sentences expressing a motor content. The possibility to recognize actions, regardless of the modality through which they are presented endowed with the mirror neuron system, makes this system a possible neural substrate not only for social interactions, but also, as recently proposed, for empathy with other people and the attribution of intentions to others (Gallese, 2003). F. Binkofski, G. Buccino / Journal of Physiology - Paris 99 (2006) 396–405 403 Fig. 4. Somatotopy of movement observation. Activation of cortical areas during observation of mouth (red), hand (green) and foot (blue) movements performed without (a) and with (b) a participating object. 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