43 The Mirror Neuron System: A Motor-Based Mechanism for Action and Intention Understanding

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1 43 The Mirror Neuron System: A Motor-Based Mechanism for Action and Intention Understanding giacomo rizzolatti, leonardo fogassi, and vittorio gallese abstract In this chapter we provide evidence that the cortical motor system is involved in action and intention understanding. In the first part of the chapter, we show that at the core of the cortical motor system, formed by ventral premotor and inferior parietal cortex, there are vocabularies of motor acts, such as grasping, holding, and breaking. Neurons that form these vocabularies code the goal of motor acts independent of how the goal is achieved. Many of these motor neurons also respond to the observation of the same motor acts they motorically code (mirror neurons). In the second part, we show that mirror neurons are involved in both the understanding of motor acts done by others and the understanding of the intention behind the acts. In the last part of the chapter we show that the mirror system in humans also plays a role in action and intention understanding. We conclude by presenting data suggesting that some of the deficits present in the autistic syndrome could be caused by an impairment of the mirror system. Traditionally, it has been assumed that understanding actions done by others, and even more so their intentions, occurs by applying a kind of reasoning not much different from that used to solve a logical problem. According to this view, when witnessing the actions of others, we process the actions with our sensory system; this information is then elaborated by some sophisticated cognitive apparatus and compared with other similar, previously stored data. At the end of this process, we know what others are doing and why. Such complex cognitive operation likely occurs in many situations, for example, when the behavior of the observed person is difficult to interpret (Brass, Schmitt, Spengler, & Gergely, 2007). et the simplicity and lack of effort with which we usually understand what the others are doing suggest an alternative solution. The actions done by others, giacomo rizzolatti, leonardo fogassi, and vittorio gallese Dipartimento di Neuroscienze, Università di Parma, Parma, Italy. after being processed in the observer s visual system, are directly mapped on his or her motor representations without any need of cognitive mediation. Strong evidence in favor of the existence of a direct mechanism of understanding others actions by matching them on the observer s own motor system came from the discovery of mirror neurons (MNs), a class of visuomotor neurons that discharge both when a monkey performs goal-related motor acts (e.g., grasping) and when it observes or hears another individual (monkey or human) doing similar acts. Neurons with these properties are found in the rostral sector of the ventral premotor cortex (area F5) and in a sector of the posterior parietal cortex (essentially corresponding to area PFG) that is anatomically connected with area F5. Thus, premotor and parietal MNs form a cortical mirror neuron system that translates sensory information about biological actions into a motor format. There is evidence that in addition to the parietofrontal mirror neuron system, there are other mirror systems, at least in humans. One, most likely present also in monkeys, is involved in translating observed emotions into a visceromotor pattern that expresses the same emotions (see Gallese, Keysers, & Rizzolatti, 2004). In addition, humans are endowed with a mirror system for phonemes (Fadiga, Craighero, Buccino, & Rizzolatti, 2002) and one for coding non-goal-directed movements (Fadiga, Fogassi, Pavesi, & Rizzolatti, 1995). In the present chapter, we will focus on the parietofrontal mirror system for actions. We will first review the anatomical and functional properties of the mirror system in monkeys and humans and address the issue of how action is represented within primates cortical motor system. We will then discuss a neurophysiological model of how actions and the intentions that promote them are understood. Finally, we will discuss some implications of this model for our understanding of autism. rizzolatti et al.: the mirror neuron system 625 Gazzaniga_43_Ch43.indd 625 3/12/2009 5:42:43 PM

2 1 Mirror neuron system in monkeys Anatomy of the Mirror Neuron System MNs were first discovered in area F5, which occupies the rostralmost sector of ventral premotor cortex. This region has recently been parcellated (Nelissen, Luppino, Vanduffel, Rizzolatti, & Orban, 2005; Belmalih et al., 2007) into three sectors occupying the cortical convexity (F5c), the posterior bank of the inferior limb of the arcuate sulcus (F5p), and the fundus of the inferior limb of the arcuate sulcus (F5a) (figure 43.1). MNs are generally found in area F5c. Parietal MNs have been found in the rostral part of the inferior parietal lobule (IPL) convexity, particularly in area PFG (Pandya & Seltzer, 1982; Gregoriou, Borra, Matelli, & Luppino, 2006), and in the anterior intraparietal area (AIP). Both these areas are connected with the cortex located inside the superior temporal sulcus (STS), including two areas that are selectively active during hand action observation: STPm and LB2 (Nelissen et al., 2005; Perrett et al., 1989). The first one is specifically connected with PFG, while the other, which is also shape sensitive, conveys information to AIP. Hodological studies (Matelli, Camarda, Glickstein, & Rizzolatti, 1986; Rozzi et al., 2006) showed a reciprocal pattern of connectivity between areas PFG, AIP, and F5. Given the similarity between the functional properties of premotor and parietal MNs, these anatomical data corroborate the idea that areas F5, PFG, and AIP constitute the mirror system for action. As far as the STS areas are concerned, although fundamental for providing visual information on biological motion, they cannot be considered as part of the mirror system in a strict sense, because they do not appear to have motor properties. Goal-Relatedness and Goal-Chaining in the Ventral Premotor Cortex and in the Inferior Parietal Lobule The functional properties of MNs can be better understood by framing them within the conception that the basic organization of the cortical motor system is in terms of goal-directed movements (Rizzolatti, Luppino, & Matelli, 1988; Rizzolatti, Fogassi, & Gallese, 2000; Crutcher & Alexander, 1990; Alexander & Crutcher, 1990; Kakei, Hoffman, & Strick, 1999, 2001; Hoshi & Tanji, 2000) and not in terms of elementary body part displacements, as was classically thought. Goal-directed movements (i.e., motor acts) are the nuclear building blocks around which action is organized and understood (Rizzolatti et al., 1988; Murata et al., 1997; Raos, Umilta, Fogassi, & Gallese, 2006; Umiltà et al., 2008). Particularly important for establishing this concept have been the studies in which single neurons were recorded in a naturalistic context. These studies showed that, typically, the discharge of F5 neurons correlates much better with a motor act than with the movements forming it. Thus many neurons discharge when a motor act (e.g., grasping) is performed with effectors as different as the right hand, the left hand, or the mouth. Furthermore, for the vast majority of neurons, the same type of movement (e.g., an index finger flexion) that is effective in triggering a neuron during a motor act (e.g., grasping) is not effective during another one (e.g., scratching). By using motor act as classification criterion, F5 neurons were subdivided into various categories such as grasping- Figure 43.1 Lateral view of the monkey brain showing the parcellation of the motor and the posterior parietal cortex. The areas located within the arcuate and the intraparietal sulcus are shown in an unfolded view of these sulci in the left and right parts of the figure, respectively. For the nomenclature and definition, see Rizzolatti et al. (1998), Nelissen et al. (2005), and Gregoriou et al. (2006). Abbreviations: AI, inferior arcuate sulcus; AS, superior arcuate sulcus; C, central sulcus; IP, intraparietal sulcus; IO, inferior occipital sulcus; L, lateral fissure; Lu, lunate sulcus; P, principal sulcus; STS, superior temporal sulcus. 626 motor systems Gazzaniga_43_Ch43.indd 626 3/12/2009 5:42:43 PM

3 with-the-hand-and-the-mouth neurons, grasping-withthe-hand neurons, holding neurons, tearing neurons, and manipulating neurons. In each class, many neurons (about 80%) code specific types of hand shaping, such as precision grip (the grip type most represented), whole hand prehension, and finger prehension. Whether they are specific or not for a certain type of prehension, neurons show a variety of temporal relations with the prehension phases. Some neurons discharge during the whole motor act, sometimes starting to fire at stimulus presentation. Some other neurons are mostly active during the opening of the fingers, and some are mostly active during finger closure (see Jeannerod, Arbib, Rizzolatti, & Sakata, 1995). On the basis of these properties, it has been suggested that F5 contains a vocabulary (a storage) of motor act representations. The vocabulary is constituted by words, each of which is represented by a set of F5 neurons. Some words indicate the general goal of a motor act (grasping, holding, tearing, etc.). Other words indicate the way in which a specific motor act must be executed (e.g., precision grip or finger prehension). Finally, other words are concerned with the temporal segmentation of the motor act into smaller chunks, each coding a specific phase of the grip (e.g., hand opening, hand closure). A crucial demonstration of this notion was recently achieved by Umiltà and colleagues (2008). In this study, hand-related neurons were recorded from premotor area F5 and the primary motor cortex (area F1) in monkeys that had been trained to grasp objects using two different tools: normal pliers and reverse pliers (figure 43.2A). These tools require opposite movements to grasp an object: With normal pliers, the hand has to be first opened and then closed, as when grasping is executed with the bare hand; with reverse pliers, the hand has to be first closed and then opened. The use of the two tools enabled the researchers to dissociate the neural activity related to hand movement from that related to the goal of the motor act. All tested neurons in area F5 and half of neurons recorded from the primary motor cortex discharged in relation to the accomplishment of the goal of grasping when the tool closed on the object regardless of whether in this phase the hand opened or closed, that is, regardless of the movements that were employed to accomplish the goal (figure 43.2B). These data indicate that goal coding is at the basis of the organization of grasping in area F5 and also in the primary motor cortex, although to a minor extent. Goal coding is therefore not an abstract, merely mentalist and experienceindependent property, but a distinctive functional feature upon which the cortical motor system is organized. An organization based on goal-directed hand motor acts is also present in AIP and in PFG (Murata et al., 2000; Fogassi et al., 2005). In both these areas, there are neurons that code specific motor acts and specific types of grips. At present, there are no systematic studies in which the functional properties of these areas have been compared with F5. As far as one can deduce from the available studies, there are strong similarities between neurons with motor properties in these areas (Raos et al., 2006). Taken together, these data indicate that the rostral part of the inferior parietal lobule is functionally part of the motor system in the same way as the premotor areas that belong to it. Recent data by Fogassi and colleagues (2005) showed that the discharge of IPL neurons coding grasping is influenced by the action in which grasping is embedded. In this study, PFG grasping neurons were tested in two main conditions. In one, the monkey reached for and grasped a piece of food located in front of it and brought the food to its mouth. In the other, the monkey reached for and grasped an object and placed it into a container (figure 43.3A). The results showed that the majority of the recorded neurons discharged with a different intensity depending on the final goal of the action (eating or placing) in which grasping was embedded ( actionconstrained neurons), (figure 43.3B). A series of controls for grasping force, kinematics of reaching movements, and type of stimuli showed that neuron selectivity was not due to these factors. Thus, the differential discharge of these grasping neurons appeared to reflect the goal of the action of which the motor act was part. A similar organization has recently been reported for area F5 (Fogassi et al., 2007). These neural properties suggest that most neurons of the PFG-F5 circuit code individual motor acts (e.g., grasping) in prewired chains, each of them coding a specific action (e.g., eating). This organization is very appropriate for providing fluidity to action execution, because each neuron not only codes a specific motor act, but, being embedded into a specific action, is also linked with neurons that code the next motor acts and possibly facilitates them. In favor of a model that assumes a facilitatory interaction between neurons forming a given chain is the organization of the receptive fields of IPL. For example, there are IPL neurons that respond to passive stimulation of the hand, flexion of the forearm, and discharge during mouth grasping (okochi, Tanaka, Kumashiro, & Iriki, 2003; Rozzi, Ferrari, Bonini, Rizzolatti, & Fogassi, 2008). These data support the existence of chains of neurons that code specific actions such as that of bringing food to the mouth. Functional Properties of MNs As has already been stated, mirror neurons are a distinct class of visuomotor neurons that discharge both when individuals perform a specific motor act and when they observe the same motor act done by another individual (figure 43.4). Among the motor acts that they code both visually and motorically, the most rizzolatti et al.: the mirror neuron system 627 Gazzaniga_43_Ch43.indd 627 3/12/2009 5:42:43 PM

4 Figure 43.2 Examples of F5 neurons active during execution of grasping with normal and reverse pliers. (A) Illustration of the experimental paradigm. To grasp the object with the normal pliers (upper part), the monkey has to close its hand, while to grasp the object with the reverse pliers (lower part), the monkey has to open its hand. (B) Two neurons recorded in area F5. Rasters and histograms are aligned with the end of the grasping closure phase (asterisk). The traces below each histogram indicate the hand position, recorded with a potentiometer, expressed as function of the distance between the pliers handles. When the trace goes down, the hand closes; when the trace goes up, it opens. The values on the vertical axes indicate the voltage change measured with the potentiometer. (Modified from Umiltà et al., 2008.) represented are grasping, holding, manipulating, and tearing. Unlike another category of visuo-motor neurons that are present in area F5 ( canonical neurons ), (Murata et al., 1997; Raos et al., 2006), they do not fire in response to simple presentation of objects, including food. The observation of intransitive motor acts, including mimed motor acts, is also ineffective. Mirror neurons show a close relationship between their visual and motor responses. Using as classification criterion the congruence between the executed and observed motor acts that are effective in triggering them, mirror neurons have been subdivided into two broad classes: strictly congruent and broadly congruent neurons (Gallese, Fadiga, Fogassi, & Rizzolatti, 1996). They are defined as strictly congruent when 628 motor systems Gazzaniga_43_Ch43.indd 628 3/12/2009 5:42:44 PM

5 Figure 43.3 Examples of the activity of parietal motor neurons during execution of two different actions. (A) Apparatus and paradigm used for the motor task. In one condition (grasping for eating), the monkey reached for and grasped a piece of food located on a plane in front of it (1) and brought the food to its mouth (2a). In another condition (grasping for placing), the monkey reached for and grasped an object located in front of it (1) and placed the object into a container (2b). In the first condition, the monkey ate the food that it had brought to the mouth; in the second condition, the monkey was rewarded after correct accomplishment of the task. (B) Activity of three IPL neurons during grasping in the two experimental conditions. Unit 67 discharges were stronger during grasping to eat than during grasping to place, Unit 161 discharges were stronger during grasping to place. Unit 158 does not show any difference in discharge between the two conditions. Rasters and histograms are aligned with the moment when the monkey touched the object or food to be grasped. Red bars: Monkey releases the hand from the starting position. Green bars: Monkey touches the container. Abscissa: Time, bin = 20 ms; Ordinate: Discharge frequency in spikes per second. (Modified from Fogassi et al., 2005.) the observed and executed effective motor acts are identical in terms of goal (e.g., grasping) and in terms of the way in which that goal is achieved (e.g., precision grip). In contrast, mirror neurons are defined as broadly congruent when there is a similarity, but not identity, between the observed and executed effective motor acts. Among the different types of broadly congruent neurons, the most common is constituted of neurons that become active during the execution of a specific motor act made by the monkey (e.g., grasping, holding, or manipulating) but visually respond to more than one motor act (e.g., manipulation and grasping). In the first studies on mirror neurons, it was reported that these neurons do not discharge during the observation of goal-directed actions done by using tools (Gallese et al., 1996; Rizzolatti, Fadiga, Gallese, & Fogassi, 1996). Subsequently, however, it was shown that following a relatively long period during which monkeys observed the experimenters performing actions using tools, some mirror neurons respond, although weakly, also to this type of action (Rizzolatti & Arbib, 1998). More recently, Ferrari, Rozzi, and Fogassi (2005) reported that in a specific ventral sector of F5, there are neurons that discharge very vigorously to the observation of tool use (e.g., a stick or a pair of pliers). It is not clear whether these neurons, like those previously observed, derived this property because of prolonged action observation. The most widely accepted hypothesis on the functional role of mirror neurons is that they play a role in understanding the goal of the observed motor acts (Rizzolatti et al., 2000). The proposed mechanism is the following: individuals know the outcome of their motor acts. Thus, when the mirror neurons of an observing individual, which code a rizzolatti et al.: the mirror neuron system 629 Gazzaniga_43_Ch43.indd 629 3/12/2009 5:42:44 PM

6 Figure 43.4 Example of the activity of an F5 mirror neuron during the observation of a grasping movement performed by another monkey (A) or an experimenter (B) and during execution of grasping by the recorded monkey (C ). (Modified from Rizzolatti et al., 1996.) given motor act (e.g., grasping), discharge in response to the observation of that motor act (grasping) done by another individual, the observer understands its goal, because that discharge corresponds to the one that occurs when the observer wants to achieve the same goal. To provide evidence in favor of the view that mirror neurons play a role in understanding motor acts done by others, neurons responses were investigated when the monkeys could comprehend the goal of a motor act without actually seeing it. If mirror neurons truly mediate understanding, their activity should reflect the meaning of the motor act rather than its visual features. Two series of experiments were carried out for this purpose. The first series tested whether mirror neurons could recognize motor acts merely from their sounds (Kohler et al., 2002). The activity of mirror neurons was recorded while a monkey was observing a motor act, such as ripping a piece of paper or breaking a peanut shell, that is normally accompanied by a distinctive sound. Then the monkey was presented with the sound alone. It was found that many mirror neurons that had responded to visual observation of acts accompanied by sounds also responded to the sound alone. These neurons were named audiovisual mirror neurons. In the second series of experiments, the researchers hypothesized that if mirror neurons are involved in understanding a motor act, they should also discharge when the monkey does not actually see the motor act but has sufficient clues to create a mental representation of it. Therefore, F5 mirror neurons were tested in two conditions. In one, the monkey was shown a fully visible motor act directed toward an object ( full vision condition). In the other, the monkey saw the same act but with its final critical part hidden ( hidden condition) (Umiltà et al., 2001). The results showed that more than half of F5 mirror neurons also discharged in the hidden condition. An example is shown in figure These experiments strongly support the notion that the activity of mirror neurons underpins the understanding of motor acts. Even when the motor act comprehension is possible on a nonvisual basis, such as via sound or nonlinguistic 630 motor systems Gazzaniga_43_Ch43.indd 630 3/12/2009 5:42:44 PM

7 Figure 43.5 Example of a mirror neuron responding during observation of grasping in both full vision and hidden condition (A and C ). Observation of goal-directed or mimed grasping, respectively, in full vision (B and D). Observation of goal-directed or mimed grasping, respectively, in the hidden condition. In every panel, from top to bottom, rasters and histogram and the schematic drawing of the experimenter motor act are shown. The gray frame in conditions B and D represents a screen interleaved between the monkey and the experimenter hand in the two hidden conditions. The asterisk indicates the location of a stationary marker that was attached at the level of the crossing point where the experimenter s hand disappeared behind the screen in the hidden conditions. The colored line above each raster represents the kinematics of the experimenter s hand movement; the downward deflection of the line means that the hand is approaching the stationary marker (the minimum corresponding to the moment in which the hand is closest to the marker). Histograms bin width = 20 ms. (Modified from Umiltà et al., 2001.) rizzolatti et al.: the mirror neuron system 631 Gazzaniga_43_Ch43.indd 631 3/12/2009 5:42:44 PM

8 mental representation, mirror neurons equally discharge, signaling the goal of the motor act. Early studies on mirror neurons examined the dorsal most sector of F5, where hand motor acts are mostly represented. Recently, a study was carried out on the properties of neurons located in the most ventral part of F5, where neuron activity is mostly related to mouth actions (Ferrari, Gallese, Rizzolatti, & Fogassi, 2003). The results showed that two classes of mouth mirror neurons could be distinguished: ingestive and communicative mirror neurons. Ingestive mirror neurons, which represent the majority of mouth mirror neurons, respond to the observation of motor acts related to ingestive functions (e.g., grasping food with the mouth). Virtually all of them show a good correspondence between the effective observed and the effective executed motor act. More intriguing are the properties of the communicative mirror neurons. For them, the most effective observed motor act is a communicative gesture, such as lip smacking. However, most of them strongly discharge also when the monkey actively performs an ingestive motor act. The presence of a motor response during both communicative and ingestive motor acts is rather intriguing. However, it could be explained by ethological observations suggesting that in evolution, monkeys communicative gestures derived, at least in part, from ingestive motor acts (Van Hoof, 1962, 1967; Maestripieri, 1996). Intention understanding Before we discuss the role of mirror neurons in intention understanding, it is important to define the terms motor act and motor action. Motor act describes a movement or, most commonly, a series of movements performed to achieve a goal (e.g., grasping an object). Motor action describes a series of motor acts (e.g., reaching, grasping, bringing to the mouth) that allow individuals to fulfill their intention (e.g., eating). When an individual observes a motor act, he or she understands the what of the motor act (e.g., grasping an object) but typically is also able to make inferences about why the motor act is being performed (e.g., grasping for eating), that is, the intention behind the action of which that motor act is part. As was described above, grasping neurons in both parietal and premotor cortex discharge with a different intensity according to the final goal of the action in which the grasping act is embedded (action-constrained neurons). Further experiments investigated whether action-constrained neurons also had mirror properties and whether their visual response during grasping observation was influenced by the action goal in which grasping was embedded (Fogassi et al., 2005, 2007). To this purpose, neurons were tested in the same two conditions that were used for studying their motor properties. Instead of grasping objects, monkeys observed the experimenter performing the two actions (grasping for eating and grasping for placing). The results showed that the majority of mirror neurons in the two areas were differently activated when the observed motor act belonged to one action or another. Examples are shown in figure What could be the explanation of this neuron behavior? It is very likely that when an action-constrained grasping neuron is activated by the observation of a grasping motor act inserted into its motor action, its discharge triggers the whole motor chain of the observer underpinning the same action. In this way, the observer activates an internal motor representation of the action that the observed agent intends to do. Thanks to this mechanism, the observer understands the observed agent s intention. One may ask how action observation can activate the appropriate motor chain when the monkey actually sees only the first motor act of it. A systematic study of this problem has not been done. It is clear, however, from the grasping neuron behavior that an important factor in determining the neuron discharge is the type of stimulus with which the agent interacts. Food, for example, tends to activate eating chains as soon as the monkey sees the experimenter grasping the food. Another factor is the statistical probability of a given action. Thus, for example, in a block of trials in which grasping is always followed by placing, grasping neurons that are tuned for placing become active. It is interesting to note that in such a block of trials, if food, rather than an object, is grasped and placed into a container, grasping-to-eat neurons fire initially, then they stop firing while grasping-to-place neurons become active. Mirror-like Activity Recent data suggest that neurons in dorsal premotor and primary motor cortex discharge during execution and observation of trained arm movements directed toward a target. In one study (Cisek & Kalaska, 2005), monkeys were trained to move a cursor from a central position to a peripheral position on a screen defined by a color cue. The recorded neurons discharged both when the monkey performed the learned task and when the monkey, being still, observed another party moving the cursor in the correct direction. The discharge typically occurred at the presentation of the target and increased with the cursor movement. Unlike mirror neurons, these neurons did not require the observation of an effector-object interaction. One may postulate, however, that the cursor was an abstract substitute for a moving hand and that the occurrence of the stimulus evoked the mental representation of the hand movement. In another study (Tkach, Reimer, & Hatsopoulos, 2007) monkeys were trained to move repetitively a cursor to targets 632 motor systems Gazzaniga_43_Ch43.indd 632 3/12/2009 5:42:44 PM

9 Figure 43.6 Examples of visual responses of IPL mirror neurons during the observation of grasping-to-eat and grasping-to-place conditions performed by an experimenter. (A) The paradigm is similar to that used for the motor task shown in Figure 43.3, but in this case, the two conditions are performed by the experimenter in front of the monkey, which is simply observing the scene. (B) Activity of three mirror neurons during observation of grasping in that appeared at random locations. The experiment consisted of two phases: active movement and observation. In the active movement phase, the monkey controlled the cursor, while in the observation phase, the monkey observed the replayed movements generated in the active phase. The observation phase has three conditions. In the first, both the cursor and the targets were visible; in the second, the monkey saw only the replayed targets; in the third, the monkey saw only the moving cursor but not the targets. The results showed that passive observation of the task determined a neural discharge similar to that found during task execution. The observation of the cursor without targets or of the targets without cursor gave either no responses or responses that were weaker than those found during the observation of both cursor and targets. The authors concluded that the most likely explanation of their findings is that the observation of the movements determined a covert generation of a motor command. the two experimental conditions. Unit 87 discharges are stronger during observation of grasping to eat than during observation of grasping to place, Unit 39 discharges are stronger during observation of grasping to place. Unit 80 does not show any difference in discharge between the two conditions. Rasters and histograms are aligned with the moment when the experimenter touched the object or food to be grasped. (Modified from Fogassi et al., 2005.) Mirror system in humans Anatomy of the Mirror System A large number of brain imaging studies showed that parietal and frontal areas that activate during motor acts execution are also active when an individual observes similar motor acts done by others (see Rizzolatti & Craighero, 2004). Most of these studies concerned observation of object-directed grasping movements. The regions that are activated in these studies form the grasping human mirror system. The two main nodes of this system are the inferior parietal lobule (IPL) and the ventral premotor cortex (PMv) plus the caudal part of the inferior frontal gyrus (IFG), roughly corresponding to its pars opercularis. The localization of human grasping mirror system corresponds to that of the homologous mirror system in the monkey (figure 43.7). Several experiments addressed the issue of how observed motor acts performed by different effectors are organized in rizzolatti et al.: the mirror neuron system 633 Gazzaniga_43_Ch43.indd 633 3/12/2009 5:42:45 PM

10 Figure 43.7 Lateral view of the human cortex showing the frontal (yellow and blue) and parietal (red) regions constituting the core of the grasping mirror neuron system in humans. Numbers and symbols indicate the different cytoarchitectonic areas according to the parcellation of Brodmann (1909). the human mirror system by presenting videos of motor acts performed with leg, hand and mouth (Buccino et al., 2001; Sakreida, Schubotz, Wolfensteller, & von Cramon, 2005; Shmuelof & Zohary, 2006; Wheaton, Carpenter, Mizelle, & Forrester, 2008) or using point-light displays of biological motion of different body parts (Saygin, Wilson, Hagler, Bates, & Sereno, 2004; Ulloa & Pineda, 2007). As far as the premotor cortex is concerned, the results showed that the observed leg motor acts are represented more dorsally in the ventral premotor cortex (PMv) extending across the superior frontal sulcus into the dorsal premotor cortex (PMd), and the hand motor acts are represented in an intermediate position in PMv, while the mouth motor acts are represented ventrally, extending into the IFG. There was considerable overlap between adjacent representations. While the goal of the observed motor acts in these studies was achieved mostly by distal movements, a recent study investigated the organization of reaching movements, that is, the transport phase of the hand to a particular location in space, eliminating the contribution of grasping movements (Filimon, Nelson, Hagler, & Sereno, 2007). It was found that in both observation and execution, the sector of premotor cortex that was activated was located in the cortex of the superior frontal gyrus (SFG), that is, in PMd. Thus, it appears that observation of motor acts focused on the distal part of the effector activates PMv, while when the focus is on the proximal part, activation mostly concerns PMd. The activation pattern in the parietal lobe is rather complex. The observation of goal-directed motor acts in which the focus was on distal movements showed activation of the rostral part of the cortex inside and around the intraparietal sulcus, extending into the convexity of IPL for mouth motor acts, activation of the caudal part of the same cortex but extending into the superior parietal lobule for the leg motor acts, and activation of an intermediate sector for the hand motor acts (Buccino et al., 2001). In the experiment (Filimon et al., 2007) in which the focus was on observation of the transport phase (reaching movement), the activation was located more dorsally, in the superior parietal lobule extending toward the dorsal bank of the IPS. In a recent study ( Jastorff, Rizzolatti, & Orban, 2007), video clips showing four distal motor acts (grasping, dragging, dropping, and pushing), each performed by using three different effectors (foot, hand, and mouth), were presented to volunteers. The results showed that while in PMv, the activations determined by the observed motor acts were clustered according to the effector used, independently of their positive (grasping and dragging) or negative (dropping and pushing) behavioral valence, in the parietal cortex, the organization followed another principle: The observed motor acts were found to be clustered according to their valence, regardless of whether they were done with the mouth, hand, or foot. The most activated region corresponded to putative human AIP, extending ventrally to the inferior parietal lobule and dorsally to the superior parietal lobule. Motor acts with negative valence were represented dorsally, while those with positive valence ventrally. It can be hypothesized that this parietal organization, by generalizing the motor act valence across effectors, allows a unified understanding of the observed behavior. In addition to an organization based on the valence of the motor act, the parietal lobe activation also showed a coarse effector-based organization. The strongest activations for foot motor acts were located dorsally, and those for mouth 634 motor systems Gazzaniga_43_Ch43.indd 634 3/12/2009 5:42:45 PM

11 2 3 motor acts were located ventrally, well below AIP. Activations for hand motor acts were the strongest in the center of the responsive region, which also responds to foot acts. It has been suggested ( Jastorff et al., 2007) that the valencerelated organization is based on a motor scaffold and that the representation of the observed motor acts that are typically performed with the hand becomes active also when they are performed with other effectors. Another issue that has been recently addressed (Gazzola, Rizzolatti, Wicker, & Keysers, 2007; Peeters et al., submitted) is whether the observation of tool use or robotic arms activates the same circuit that becomes active during the observation of motor acts done with natural effectors. The results of these studies showed that the basic parietopremotor circuit that becomes active during the observation of hand grasping is also active during the observation of tool actions. In addition, however, it was shown (Peeters et al., submitted) that the observation of actions performed with tools activates a specific region in the inferior parietal lobule, corresponding to the rostral inferior part of the supramarginal gyrus. The two parietal regions that are activated by the observation of tools and robotic arms could underlie two different ways in which tool use is understood. The sector around the intraparietal sulcus could mediate an association between a tool and the tool use outcome without an understanding of tool functioning. In contrast, the rostral supramarginal gyrus could be involved in the uniquely human capacity of understanding the tool use in terms of its functioning. It is interesting to note that the rostral supramarginal gyrus is the part of the inferior parietal lobule that is most frequently damaged in patients with ideomotor apraxia (see Leiguarda & Marsden, 2000; Wheaton & Hallett, 2007). Plasticity of the Mirror System Is the mirror system modulated by motor experience? There is clear evidence that the observation of motor acts that are richly represented in the observer s motor repertoire determines a stronger activation of the mirror system than does the observation of novel motor behaviors (Casile & Giese, 2006; Rethler et al., 2007). In particular, in a functional magnetic resonance imaging (fmri) study, Calvo-Merino, Glaser, Grezes, Passingham, and Haggard (2005) demonstrated that the observation of actions performed by others results in different cortical activations depending upon the specific motor competence of the tested individuals. Participants, who included classical dancers, dancers of Capoeira, and people who had never taken a dancing class, were shown a video of Capoeira dance steps. The sight of the dance steps of Capoeira caused a greater activation of the mirror system in the Capoeira dancers than in either the classical dancers or the beginners. Conversely, a video showing classical dance steps resulted in a much stronger activation of the classical dancers mirror system compared to those of the Capoeira dancers and the beginners. In a further experiment, the same researchers (Calvo- Merino, Grezes, Glaser, Passingham, & Haggard, 2006) tried to understand whether the differences in the activation found in the previous experiment were due to motor or visual familiarity with the observed movements. The results showed that the mirror system was activated more strongly by the sight of the dance steps executed by the dancers of the same sex of the observer, indicating, therefore, that the activation was regulated by motor practice and not by visual experience, given the fact that the latter was the same for both sexes. The data by Calvo-Merino and colleagues (2005, 2006) were extended by Cross, Hamilton, and Grafton (2007) in a study in which expert dancers learned and rehearsed novel, complex whole-body dance sequences for five weeks. Brain activity was recorded weekly by fmri as dancers observed and imagined performing different movement sequences. Half of these sequences were rehearsed, and half were unpracticed control movements. Critically, activation of the mirror system was modulated as a function of dancers motor experience. These data show that the mirror system codes the observed actions by mapping them onto corresponding motor representations of the observer. But how would the mirror system respond to the observation of hand actions if the observer never had hands or arms? Two aplasic individuals, born without arms or hands, were scanned while they observed hand motor acts (Gazzola, van der Worp, et al., 2007). The results showed activations in the parietofrontal circuit of aplasic individuals while they watched hand motor acts. This finding demonstrates the brain s capacity to mirror acts that deviate from the typical motor organization by recruiting brain cortical representations involved in the execution of motor acts that achieve corresponding goals by using different effectors. The Mirror System and Intention Understanding in Humans Recent experiments showed that besides understanding of motor acts, the mirror system is also involved in understanding the intention behind the observed motor acts. Evidence in this sense has been provided by an fmri study (Iacoboni et al., 2005). In this study, there were three conditions. In the first one (called context ), participants saw a scene with objects (a teapot, a mug, a plate with some food on it) arranged as if a person was ready to have breakfast or arranged as if a person had just finished having breakfast; in the second condition (called action ), participants were shown a hand that grasped a mug without any context; in the third (called intention ), participants saw the same hand motor act within the two different contexts. The 4 rizzolatti et al.: the mirror neuron system 635 Gazzaniga_43_Ch43.indd 635 3/12/2009 5:42:45 PM

12 5 6 context suggested the intention of the agent, that is, grasping the cup for drinking or grasping it for cleaning. The results showed that in both action and intention conditions, there was an activation of the mirror system. The comparison between intention and action conditions showed that the understanding of the intention of the agent determined a marked increase in activity of the right IFG. Interestingly, the observation of grasping of the cup to drink produced a stronger activation than did the observation of grasping done to clean. This result is similar to findings in monkeys (see above) showing that the number of neurons that code grasping for bringing to the mouth largely exceeds the number of neurons that code grasping for putting an object into a container. In another fmri study, based on repetition suppression paradigm, participants were instructed to observe repeated movies showing the same action outcome (such as opening or closing a box) achieved by using the same or different kinematics. The results showed that the right inferior parietal and right inferior frontal cortex responses were suppressed by the observation of the same action outcome, independent of the means used to achieve it. This finding has been interpreted as an evidence of the involvement of the mirror system in intention understanding (Hamilton & Grafton, 2008). In conclusion, these data show that the intentions behind the actions at least of basic actions of others can be recognized through the mirror mechanism. This does not imply, of course, that other, more cognitive ways of reading minds do not exist (see Frith & Frith, 2007). However, there little doubt that the mirror mechanism is one of the most basic and possibly the most basic mechanism for intention understanding. More recently, an fmri study investigated the neural basis of human capacity to differentiate between actions that reflected the intention of the agent (intended actions) and actions that did not reflect it (nonintended actions). Participants were shown video clips of a variety of actions done with different effectors, each in a double version: one in which the actor achieved the purpose of his or her action (e.g., pouring the wine) and one in which the actor performed a similar action but failed to reach the goal because of a motor slip or a clumsy movement (e.g., spilling the wine) (Buccino et al., 2007). The results showed that both types of actions activated the mirror system. The direct contrast nonintended versus intended actions showed activation in the right temporoparietal junction, left supramarginal gyrus, and mesial prefrontal cortex. The converse contrast did not show any activation. It was concluded that the capacity to understand when an action is nonintended is based on the activation of attention areas signaling unexpected events in spatial and temporal domains (Corbetta & Shulman, 2002; Coull, 2004; Mitchell, 2008). These results indicate that when an individual observes an unexpected motor act, such as a motor slip, his cortical machinery, besides signaling the observed motor act, also signals the strangeness of the motor act outcome. The Mirror System, Motor Cognition, and Autism Autistic children display a striking inability to relate themselves to people in ordinary ways. According to Kanner (1943), this represents the fundamental feature of autism. However, in the same seminal paper, Kanner reported that almost all mothers [...] recalled their astonishment at the children s failure to assume at any time an anticipatory posture (Kanner s italics) preparatory to being picked up. Unlike typically developing children, autistic children use motor strategies that basically rely on feedback information rather than on feedforward modes of control. Such motor disturbance prevents autistic children from adopting anticipatory postural adjustments (Schmitz, Martineau, Barthélemy, & Assaiante, 2003). The theoretical relevance of these findings has been clarified by a recent electromyelographic (EMG) study (Cattaneo et al., 2008) showing that high-functioning autistic children are unable to organize their own motor acts in intentional motor chains as typically developing children do. Participants in this study were typically developed (TD) and highfunctioning autistic children who were required both to execute and to observe two different actions: grasping with the right hand a food item placed on a plate, bringing it into the mouth, and eating it or grasping a piece of paper placed on the same plate and putting it into a box (figure 43.8A). During the execution and observation conditions of both actions, the activity of the mouth-opening mylohyoid muscle (MH) of the participants was recorded by using EMG surface electrodes. The results showed that during the execution and observation of the eating action, a sharp increase of MH activity was recorded in TD children, starting well before the food was grasped. No increase of MH activity was present during the observation of the placing action. This means that one of the muscles that are instrumental to accomplish the action final goal (opening the mouth to eat a piece of food) is already activated during the initial phases of the action. The motor system anticipates the consequences of the action final goal (to eat), thus directly representing the action intention, both when the action is executed and when the action is observed being done by others. In contrast with TD children, high-functioning autistic children showed a much later activation of the MH muscle during eating action execution and no activation at all during eating action observation (figures 43.8B and 43.8C ). These results reveal that children with autism are impaired in chaining sequential motor acts within a reaching-to-grasp-to-eat intentional action, a mechanism 636 motor systems Gazzaniga_43_Ch43.indd 636 3/12/2009 5:42:45 PM

13 A B 1 B 2 typically-developing children rectified mylohyoid EMG eat place time (s) rectified mylohyoid EMG eat place 0.01 reach grasp bring rectified mylohyoid EMG eat place time (s) rectified mylohyoid EMG eat place 0.01 reach grasp bring autistic children rectified mylohyoid EMG eat place time (s) rectified mylohyoid EMG eat place 0.01 reach grasp bring rectified mylohyoid EMG eat place time (s) rectified mylohyoid EMG eat place 0.01 reach grasp bring Figure 43.8 Differential activation of a mouth-opening muscle during execution and observation of two actions in typically developing and autistic children. (A) Schematic representation of the two actions executed and observed by the two groups of subjects. Upper part: The individual reaches for and grasps a piece of food located on a touch-sensitive plate, brings it to the mouth, and eats it. Lower part: The individual reaches for and grasps a piece of paper located on the same plate and puts it into a container placed on the shoulder. (B) Left: Time course of the EMG activity of the mylohyoid muscle during execution of grasping for eating (red) and grasping for placing (blue). Vertical bars indicate the standard error. The curves are aligned (dashed vertical line) with the moment in which the object is lifted from the touch-sensitive plate. Right: Mean EMG activity of the same muscle in three epochs of the two actions. Vertical bars indicate 95% confidence intervals. (C ) Left: Time course of the EMG activity of the mylohyoid muscle during observation of grasping for eating (red) and grasping for placing (blue). Other conventions as in B1. Right: Mean EMG activity of the same muscle in three epochs of the two observed actions. Other conventions as in B. (Modified from Cattaneo et al., 2008.) rizzolatti et al.: the mirror neuron system 637 Gazzaniga_43_Ch43.indd 637 3/12/2009 5:42:46 PM

14 7 that most likely reflects the chained organization of the parietal cortex described in the monkey (see above) (Fogassi et al., 2005). This impairment is mirrored in the action observation condition and most likely accounts for the difficulty these children have in directly understanding the intention of the observed action when executed by others. Other recent studies have documented a deep impairment of the core mechanisms of motor cognition in children with autism. Two recent studies show that autistic individuals might be suffering from a dysfunction of their mirror system. Theoret and colleagues (2005) showed that, again unlike healthy controls, children with autism did not show TMS-induced hand muscle facilitation during hand action observation. Oberman and colleagues (2005) showed that children with autism, unlike healthy controls, did not show mu frequency suppression over the sensorimotor cortex during action observation. 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