Imitation, mirror neurons and autism

Article · Literature Review (PDF Available)  in Neuroscience & Biobehavioral Reviews 25(4) · July 2001 with 317 ReadsDOI: 10.1016/S0149-7634(01)00014-8 · Source: OAI

https://www.researchgate.net/publication/28763620_Imitation_mirror_neurons_and_autism

 
Justin H G Williams
 
Justin H G Williams
Institution
Department

 

Thomas Suddendorf

Thomas Suddendorf

The University of Queensland | UQ · School of Psychology

 

Andrew Whiten

David I Perrett47.07

Institution
Department

(Häijyn näköistä porukkaa...)

 

Abstract

Various deficits in the cognitive functioning of people with autism have been docu-mented in recent years but these provide only partial explanations for the con-dition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently dis-covered class of neurons in frontal cortex,'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and ‘theory of mind’ abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.


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Contents
1. Introduction: the basis of autism ...........................................................287
2. The role of early imitation ......................................................................288
3. Imitation in autism ....................................................................... .........289
4. Neurobiology of imitation .................................................................. .....289
5. The functional signi®cance of mirror neurons ...................................... 290
5.1. Speech ............................................................................ ...................290
5.2. Theory of mind ..................................................................... ............. 290
5.3. More basic intersubjective phenomena: emotional contagion and shared attention.................................................................................................... 290
5.4. Imitation ..............................................................................................291
6. Mirror neurons and autism ................................................................... 291
7. Autism, executive functions and mirror neurons ................................. .291
8. Neuroimaging mirror neurons and `theory of mind' ............................. .292
9. Testing the hypothesis ......................................................................... 292
10. Conclusion ......................................................................................... 293
References ............................................................................................... 293


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1. Introduction: the basis of autism
 
The autistic spectrum disorders are increasingly being recognised as an important cause of social disability [1]´and have been the focus of a ¯urry of research in the last decade [2± 5]. Here, we suggest that juxtaposing some of these psychological ®ndings with recent discoveries in neurobiology offers the prospect of a new and potentially powerful model of both early social functioning and the disorders in it that are associated with autism.
 
The autistic spectrum disorders are characterised by impairments in social interaction, imaginative ability and not specific to the condition such as global developmental delay, aggression or sleep disturbance.
 
2. The role of early imitation
 
The possibility that deficits in imitation might be particularly intimately connected with the earliest developmental stages of autism was ®rst set out systematically
by Rogers and Pennington [21]. According to these authors, imitation might fill at least two of the three gaps left by the ToM explanation noted above: first, imitation has characteristics suggesting that the mechanisms underlying it could be precur- sors (perhaps the first that can be identified in infancy) to full ToM; and second, imitation may also be fundamental to the other, broader kinds of social deficits seen in autism. The relationship between imitation and the third group of (largely non-social) deficits listed above is one we shall discuss once other parts of our model have been explained.
 
Rogers and Pennington [21] collated existing empirical evidence of imitation defi-cits in autism, which we discuss in the following section. First, however, some key theoretical bases for a link between imitation mechanisms and later developing ToM need to be recognised.
 
Imitation and the attribution of mental states bear some fundamental resemblan-ces [22,23]. Both involve translating from the perspective of another individual to oneself. Thus in accurately reading the belief of another, one essentially copies the belief into one's own brain, creating a `second-order' representation of the other's primary representation of the world (and, of course, not confusing it with one's own beliefs, at least in the normal case). Conversely, in imitating, one must convert an action plan originating from the other's perspective into one's own. A more specific linkage between imitation and ToM is implied by the fact that one of the two principal models of how ToM operates is designated the `simulation' theory [24]. Its rival is the `theory theory', which sees the child acting somewhat like a young scientist, observing patterns of behaviour in others, and developing theories about mental states to explain and predict them. The simulation theory instead proposes that children come to read minds by `putting themselves in the other's shoes', and using their own minds to simulate the mental processes that are likely to be operating in the other.
 
`Acting as if you are the other's simulation is thus at the covert, mental level akin to what is involved at the overt level in imitation. Current views include the possi-bility that both `simulation theory' and `theory-theory' processes are at work in the human case [25].
 
Meltzoff and Gopnik [26] reviewed evidence for imitation in the earliest phase of infancy and proposed that this could provide a key starting-state for the develop-ment of ToM. The nub of their hypothesis is that the new-born's capacity to trans-late between the seen behaviour of others and what it is like to perform that same behaviour offers a crucial basis for recognising the linkage between mental states and actions.
 
There are, thus,substantial theoretical reasons for considering imitation as a prime candidate for the building of a ToM. Rogers and Pennington's theory [21] was that at the root of autism is `impaired formation/co-ordination of specific self-other re-presentations', manifest first in impaired imitation,followed by a cascade of impair- ments in emotion-sharing, joint attention and pretend play (thus including the broad range of socialde®cits), and ToM. What, then, is the evidence for imitation being affected in autism?
 
3. Imitation in autism
 
Evidence for an imitative de®cit in autism has been reviewed elsewhere [21, 27 ± 29]. None of these reviews is comprehensive,but together they cite 21 experimen-tal studies of the imitative competence of individuals with autism.The studies have been heterogeneous with respect to the mental ages tested, the types of control groups used and the imitation tests themselves, but only two studies did not find an imitative deficit in the autistic samples and then possibly because of the simpli-city of the tasks,leading to ceiling effects. Smith and Bryson [27] conclude that the literature shows a `consistent fnding that people with autism do not readily imitate the actions of others'. Furthermore it is worth noting the magnitude of the imitative deficit. For instance, Rogers et al.[30] detected group differences of approximately 1.5 standard deviations between the autistic and control group means. More re-cently, Hobson and Lee [31] found that only 1 out of 16 (6%) subjects imitated the style of one of their tasks, compared to 12 out of 16 (75%) controls. A number of studies have detected significant group differences with just 10 subjects per group. The magnitude of this deficit then can be at least as great if not greater than the `theory of mind' deficit. Rogers [28] additionally notes the difficulties faced by carers in intensively teaching imitation to young children with autism.
 
Deficits in the imitation of `symbolic' elements (such as pantomiming brushing one's teeth with a non-existent toothbrush) might be expected in view of the dia-gnostic criteria; thus of special interest are those concerning basic body move-ments or gestures. These were first demonstrated by DeMeyer et al. [32] and have since been replicated in at least nine further studies [27±29].
 
Rogers [28] concludes that `every methodologically rigorous study so far pub-lished has found an autism-specific de®cit in motor imitation'. The conclusion that the imitative deficit may be operating at such a fundamental level is important to our synthesis with neurobiological findings discussed further below.
 
The reason for difficulties in imitation associated with autism remains unclear but some clues may come from an examination of the type of imitative deficit present.
 
Firstly, imitation of meaningless gestures would appear to be affected more than imitations of actions with objects [30].
 
Perhaps the use of objects in some tests may offer a `prop', helping to shape a matching response; by contrast, difficulties in copying raw gestures underlines the more basic nature of the imitative de®cit referred to earlier [33].
 
Secondly, when children with autism were asked to imitate an unconventional action with a common object (such as drinking from a teapot) they were more like-ly to make errors [27]. This again provides evidence for an imitative deficit more fundamental than that expected on the basis of other known impairments. Thirdly are reversal errors [27,29];for example,in `copying' the action of holding the hands up palm away, grasping the thumb of one hand with the other hand, autistic sub-jects tended to hold their palm towards themselves, recreating the hand view they had seen (sometimes also failing to grasp the thumb) instead of translating the perspective the other had seen [25]. Finally there are greater group differences with respect to sequences of actions than when single actions alone are being imitated [30].Together,these kinds of errors suggest that deficits may be occurring in the basic ability to map actions of others onto an imitative match by oneself [29] especially when such actions are complex.
 
Finally, there is a curious aspect of imitation-like phenomena in relation to autism, that concerns the well-known repetitive and stereotyped behaviours and speech
that may occur. These may be copied from others, including words and phrases (echolalia) and sometimes actions, that are mimicked without regard to their nor-mal goals and meanings.At first sight these phenomena seem contradictory to the notion of an imitative de®cit, but they may instead offer clues to the underlying neural dysfunction. We will discuss this in a later section, in integration with the findings on neurobiology to which we now turn.
 
4. Neurobiology of imitation
 
Patients with left frontal lobe lesions may show imitative dyspraxia [33,34]. These patients are unable to repeat actions performed by others, despite demonstrating
adequate motor control of their limbs. Furthermore, they are unable to replicate such gestures on a manikin [35].
 
This is consistent with the idea that imitation may normally rely on representation of action at a `supramodal' level [36], which is unavailable to these patients; the same lesion site will accordingly disrupt the replication of a gesture whether on the self or on another body.
 
Work at the neuronal level in non-human primates has started to indicate the path-ways by which representation of such actions may be built up. A number of diffe-rent types of specialised neuron have been identified in the superior temporal sul-cus (STS) of monkeys that are dedicated to visual processing of information about the actions of others.
 
Particular populations of cells code the posture or the movements of the face, limbs or whole body [37±41].Other classes of neurons appear to code movements as goal-directed actions and are sensitive to hand and body movements relative to objects or goals of the movements (e.g. reaching for, manipulating or tearing an object) [42 ± 45].
 
Of special relevance to our model is a subset of such action-coding neurons iden-tified in the prefrontal cortex (area F5) in monkeys [46, 47]. Such neurons will fire when the monkey performs a speci®c action, such as a precision grip, but also when an equivalent action (a precision grip, in this example) is performed by an individual the monkey is watching. These have been called `mirror neurons' (MNs) [47]. Their potential relevance to imitation is signalled by another label: `monkey see, monkey do' neurons [48]. F5 cell activity, however, does not automatically lead to motor responses and action performance, otherwise seeing actions performed would lead to obligatory copying (echopraxia).
 
The execution of actions when F5 cells are activated by the sight of actions of others, may be inhibited by mechanisms operating elsewhere in the motor pathway [49] and perhaps involving orbitofrontal cortex [50].
 
Although MNs cannot be studied directly in the same way in humans, the exis-tence of a system with the properties of MNs is supported by ingenious alternative approaches [47,51] including the use of transcranial magnetic stimulation (TMS) of human motor cortex to produce electromyographic potentials in muscle groups [52]. Observing actions involving distal finger movements but not proximal whole
arm movements selectively lowered the threshold for TMS to induce electromyographic activity in distal musculature.
 
This demonstrates input from the sight of movements to the neural system involved in motor control of the same movements.
 
Several functional imaging studies have noted that the sight of hand actions pro-duces activity in frontal regions (premotor cortex and Broca's area) [53,54], which may be homologous to F5 in the monkey [49]. In a recent fMRI study, activation of the left Broca's area during observation of finger movements became more intense when that same action was executed simultaneously [55]. These imaging
studies also reveal activity in parietal cortex. This area, along with possibly the superior temporal sulcus, also shows some evidence of mirror neuron activity ([56] and M. Iacoboni (pers. com.)).
 
5. The functional significance of mirror neurons
 
MNs appear to have the capacity to embody a `supramodal representation' of action, functioning as a bridge between higher visual processing areas and motor cortex (between seeing and doing). As yet, MNs have been investigated with res-pect to hand actions, but it seems likely that others are concerned with different actions, such as facial expression and speech, and perhaps eye movements and the higher-level abstractions [41, 42]. However, MNs have only recently been dis-covered. Their precise significance is not yet known, but some specific suggestions are particularly relevant to our discussion.
 
5.1. Speech
 
Rizzolatti and Arbib [49] have suggested that the part of the monkey brain which contains MNs dealing with hand actions has evolved to subserve speech in hu-mans, with language building on top of a `prelinguistic grammar of actions' already existing in the primate brain. By acting as a bridge between perceived and per-formed action and speech, the MN system is thus suggested to have provided
the foundations for the evolution of dialogue. Furthermore,if MNs do process audi- tory representations as they do visual ones,they may be important in representing the relationships between words and their speaker like the personal pronouns.
 
If this is true, the MN system may also provide crucial foundations ontogenetically, particularly with respect to the development of the pragmatic aspects of speech, and thence more complex aspects of language. However, not only the pragmatics of speech may depend on a functional mirror neuron system. Lack of invariance in the physical structure of phonemes gave rise to the motor theory of speech per-ception, which suggests that we hear sounds according to how we produce them [57, 58]. If MNs are an important link between the production and perception of speech or between sender and receiver [49]Ð then an intact MN system may be important for other stages of language development as well.
 
5.2. Theory of mind
 
Gallese and Goldman [59] have suggested that it may be possible to predict and also `retrodict' an observed person's mental state by constructing the appropriate mental correlates of an act once it is `reconstituted' in the observer's own MN system.They suggest that MN activation can permit the generation of an executive plan to perform an action like the one being watched, thereby getting the observer `into the mental shoes' of the observed (but see also Gallese [60]).
 
They also note this is a process that requires an ability for controlled inhibition to prevent concomitant execution of an observed action. They argue that such a mechanism is in keeping with the `simulation' model of ToM, which also requires that observed action sequences are represented in the observer `off-line' to prevent automatic copying, as well as to facilitate further processing of this high-level social information.
 
5.3. More basic intersubjective phenomena:emotional contagion and shared attention
 
Before moving on to consider the possible role of mirror neurons in autism, it is important to note that there seems no reason in principle why MNs should not address a wide range of actions and the mental states they connote. For example, since emotional states are closely linked to certain facial expressions, observation of a facial expression might result in mirrored (but mainly inhibited) pre-motor acti-vation in the observer and a corresponding `retrodicted' emotional state. Such a process might help to explain the phenomenon of emotional contagion, in which people automatically mirror the postures and moods of others [61]. This seems particularly likely in view of the close connections between STS neurons, the mir-ror neuron circuits and the amygdala [43]. Indeed, there is direct electromyogra-phic evidence that observers adopt facial muscle activity congruent with expressions witnessed even when this process is not at an overt level [62].
 
Like emotion reading [20], a capacity for shared attention has been proposed as an important precursor to full theory of mind, partly on the basis of evidence that deficits in this capacity are apparent early in the life of individuals with autism, their occurrence thus being explored as an early warning sign [16,63,64]. Here we note simply that being able to identify the focus of attention of another, or to be able to consider drawing their attention to the focus of one's own attention, is another case of being able to `stand in the other's shoes'. In shared attention, each individual's attentional focus mirrors the other, raising the prospect that MNs
could play a role in this achievement.
 
5.4. Imitation
 
In discussing the possible role of MNs in each of the above capacities, some references to imitative-like phenomena (`standing in the others shoes') have been made. It might be thought that the obvious functional role of MNs would indeed lie in imitation (in which case MN outputs would not be inhibited). However, noting that there is little evidence of imitation in monkeys [65,66] Gallese and Goldman [59] suggested that in the monkeys in which they have been identified, MNs are functioning to facilitate social understanding of others (to the extent the monkey `stands in the same `mental shoes' as the other, as Gallese and Goldman put it).
This is not argued to amount to ToM (for which there is also little evidence in monkeys [22,23]), but it may nevertheless represent the kind of foundation which permitted the evolution of ToM in humans [59].
 
However, we note there is better evidence for imitation in apes than in monkeys, and of course imitation is both evident and functionally important in our own species [66,67]. We suggest that the evolution of imitation in humans is likely to have utilised an existing MN system, even if its prior uses lay in more generalised kinds of social understanding. As mentioned earlier, fMRI with human subjects during a simple imitation task did indeed find activation in area 44 as well as in parietal cortex, suggesting that the MN system is involved in imitation in humans.
 
If Gallese and Goldman are right about the function of MNs in monkeys, certain additional capacities had to evolve before MNs could support either imitative or more advanced ToM functions. We may guess that these additional factors reject
the increased cortical volumes of great apes and humans and the representatio-nal capacities associated with them; their precise nature is a question for future research. For now, the critical hypothesis is that MNs provide a key foundation for the building of imitative and mindreading competencies.
 
Accordingly, if Rogers and Pennington were right about the linkage between imi-tation and ToM, we should, thus,expect that MNs play important roles in the whole ontogenetic cascade from early imitation to elaborated ToM. This would clearly be consistent also with Gallese and Goldmann's [59] hypothesis that MNs and ToM are linked.
 
6. Mirror neurons and autism
 
These ideas lead directly to our hypothesis that some dysfunction in the MN sys-tem might be implicated in the generation of the constellation of clinical features which constitute the autistic syndrome. The most basic hypothesis would be that there is a failure or distortion in the development of the mirror neuron system. This could be due to genetic or other endogenous causes, to external conditions ad- verse to MN functioning,or some interaction between these. Such factors might af- fect all MN groups or be confined to just certain groups such as those in the parie-tal cortex. Complete failure is not necessarily implied, for there might be merely a degree of delay or incomplete development.
 
Considering the factors discussed in previous sections, such dysfunction could prevent or interfere with imitation, or perhaps more fundamentally, lead to the `impaired formation/co-ordination of speci®c self-other representations' proposed to lie at the root of the cascade of autistic problems [21]. This in turn could explain the failure to develop reciprocal social abilities including shared/joint attention, gestural recognition and language (particularly the social/pragmatic aspects that Rogers and Pennington [21] note are the most affected), as well as breakdowns in
the development of empathy and a full ToM.
 
Such a simple `MN-dysfunction, imitation-dysfunction' model is unlikely to provide the whole story, however, insofar as we also need to explain features of repetitive, in¯exible and stereotyped behaviour and language that appears to incorporate some copying from others, in some patients with autism.
 
We would suggest that in fact these latter features are testimony to the per-ception-action linkage problems that occur in autism; they are consistent with the hypothesis that in autism, the mirror neuron system is as a whole malfunctioning. In these cases the system might be evidencing poor modulation.
 
Recall that it has been suggested that a controlled inhibitory system is essential for allowing MN's to operate `off-line' for simulation ToM to function and develop. If damage extends to such inhibitory components, then certain forms of mimicry
might occur, yet be oddly performed.
 
7. Autism, executive functions and mirror neurons
 
In recent years it has been shown that autistic individuals experience difficulties in executive functions like planning [68 ± 72]. It tends to be assumed that executive functions such as planning ability and attentional shifting are the product of deve-lopmental processes largely restricted to the individual. But it is also possible that the child learns something of these functions from others, perhaps initially in rela-tively concrete contexts, such as playing with building bricks in infancy,and then at higher levels of abstraction and over longer time frames, such as planning meals. The initial stages in such a process might correspond to some kind of `program-level' imitation [73]. There is evidence for this in three-year-old children who are able to acquire, by imitation, alternative hierarchical plans for running off a sequence of actions to complete a functional task [74]. Insofar as MNs code for actions on objects, directed towards a goal, they could be key elements in such a process [75], helping to translate perceived executive functions into praxis and then generalising them to similar situations.
 
With poor MN development, the key building blocks permitting planning functions to be acquired from the external culture might be unavailable.
 
If mirror neurons play a part in the development of executive function as well as ToM,one would expect to see a correlation between performance on tests of each of the two abilities. This has recently been demonstrated [76].The same principles may apply to the acquisition of other executive functions, such as approaches to problem solving and attentional shifting,which can be a problem for autistic child- ren [68,69]. Evidence in favour of this proposition comes from Griffiths et al. [77]. They found that apart from tests requiring rule reversal, there was no deficit of executive function in children under 4 years of age with autism. This suggests that the executive deficits are not primary but arise later on in a disrupted pattern of development. Some executive functions, including inhibition and possibly visual working memory appear to be spared in autism [4,67,78,79]. These might be functions much less easily learnt by imitation.
 
Autistic children show not only characteristic ToM and planning deficits, but also impairment in reconstructing the personal past [80]. Suddendorf [81 ± 83] has pro-posed that the executive capacity to disengage or dissociate from one's actual current state (putting it of¯ine, as it were) in order to simulate alternative states un-derlies both `theory of mind' and mental `time-travel' the ability to mentally con-struct possible (e.g. planned) events in the future and reconstruct personal events from the past. Thus, in this account mirror neurons may be implied through simulation and executive functions.
 
8. Neuroimaging mirror neurons and `theory of mind'
 
If ToM and related social de®cits in autism are the result of a poorly functioning system of mirror neurons, this might be manifest in recent neuroimaging studies
with relevant tasks. The mirror neuron region has been implicated in reading facial emotion in a normal population [84]. Similarly, a task that involved reading emotio- nal expressions from looking at images of eyes, found that individuals with autism showed less involvement of areas normally activated during emotional interpre-tation, namely the left putative mirror-neuron region (BA 44/45), the superior tem-poral gyrus (BA 22) bilaterally, the right insula and the left amygdala [85]. A recent review [86] of studies of both typical individuals and those with autism, seeking to identify sites active in ToM functions found that a well demarcated area of the pa-racingulate gyrus has been consistently implicated, as have areas of the anterior cingulate cortex but not the mirror neuron regions. The paracingulate gyrus and the anterior cingulate cortex are closely linked and receive dense serotonergic innervation, consistent with them performing a modulatory function and this could explain their involvement. One possible reason for the failure of these tasks to activate MN regions may be related to the control tasks that have been used. As these have been predominantly action-based such as following an action-based story, they would be expected to activate the MN regions as much as the ToM task, so discounting their apparent relevance.
 
9. Testing the hypothesis
 
From our hypothesis, several testable predictions ¯ow.
 
First, imitative de®cits should be apparent in autism especially where studies take place in the earliest years such as in the study by Charman et al. [87]. Particular aspects of imitation expected to be most susceptible are those where imitation involves a co-ordinated activity between different modes of sensory input, different groups of action-coding neurons and self-other visual transformations.
 
Secondly, we suggest that the McGurk effect [88] whereby the perceived sound is altered by perceiving lip movements making a different sound,may be the result of MN functioning. In this case we predict that on testing groups of children with autism, non-standard McGurk effects will be apparent.
 
A third prediction can be related to the work of Baron-Cohen et al. [64] using the CHAT screening test for autism.
 
These authors found that joint attention at 18 months was a predictive screening item for autism (focussing on siblings of individuals with autism). Our hypothesis predicts that even earlier, appropriately-sensitive screening for an imitative deficit would be predictive in this way.
 
Fourth, we would predict that imaging studies will indicate altered activation of putative MN regions in the brain during imitation tasks attempted by subjects with autism. Similarly, electrophysiologic studies will show altered muscle activity during the observation of actions, whether facial, vocal or with the hands
 
One recent study has attempted to examine mirror neurone activity in Asperger's syndrome [89].Magnetoencephalography was used to detect a decrease in the 20 Hz activity that occurred in the MN region during median nerve stimulation whilst subjects viewed an action. The study did not find a significant difference between the five Aspergers' participants and a control group. Our analysis predicts that
more extensive testing of people with autism will reveal such a difference.With the small sample size and small expected effect size (the hypothesis was tested in older individuals with the milder form of the disorder) this first study had minimal power and there was a high risk of a type two error. It is therefore important that further work is extended to larger groups with other characteristics.
 
10. Conclusion
 
The discovery of mirror neurons offers a potential neural mechanism for the imitation of actions as well as other aspects of understanding social others.
 
Evolution of this system may have been critical in the emergence of proto-culture and Machiavellian manoeuvring in the most encephalized non-human primates, followed by elaborate ToM and language in humans [90]. In the development of the human child, mirror neurons may be key elements facilitating the early imi-tation of actions, the development of language, executive function and the many components of ToM. A failure to develop an intact, sensitively regulated, mirror neuron system may therefore impair the development of these important human capabilities.
 
Our exploration of this hypothesis highlights numerous aspects of our ignorance.
 
Unanswered questions include:
 
1. What other cognitive and neural capacities work in conjunction with MNs to support imitation and ToM functions?
 
2. How do MNs relate to other social information processing neurons in performing social cognitive functions?
 
3. How physically extensive are MN functions which relate to autism? Do they just exist in Broca's area or are there such groups in locations such as parietal cortex, paracingulate gyrus and superior temporal sulcus?
 
4. Do MNs have functions in non-visual modalities as preliminary reports suggest (C. Keysers, E. Kohler, A. Umilta, V. Gallese and G. Rizzolatti, personal commu-
nication; Baker and Perrett, unpublished studies)? For example, is the sound of an action (or vocal utterance) mirrored by the same neurons as those which mirror its sight? What is the range of actions addressed by MNs?
 
Despite the various candidates suggested in the literature, a `prime mover' source of the complex cascade of impairments that characterise autism has so far proved elusive. We are suggesting that developmental delay or distortion of a mirroring system with an early age of onset could be such `prime mover'. The heterogeneity of the autistic condition may argue against a single cause, yet the commonalities of the clinical syndrome nevertheless permit the possibility of a core dysfunctional mechanism. If this mechanism is normally a precursor to a cascade of effects on other variable systems, then its dysfunction is likely to result in a quite variable cli-nical picture. Our proposal offers such a mechanism, together with some prelimi-nary evidence for its existence and empirically testable hypotheses. If it gains further empirical support, this may suggest important new avenues for both psychological and pharmacological remediative strategies.
 
References
[1] Fombonne E. The epidemiology of autism: a review. Psychol Medicine 1999; 29: 769±86.
[2] Bailey A, Philips W, Rutter M.Autism: towards an integration of clinical, genetic, neuropsychological and neurobiological perspectives. J Child Psychol Psychiatry 1996; 37: 89± 126.
[3] Cohen DJ, Volkmar F. Handbook of autism and pervasive developmental disorders. 2nd ed. New York: John Wiley & Sons, 1997.
[4] Russell J. Autism as an executive disorder. Oxford: Oxford University Press, 1997.
[5] Baron-Cohen S, Tager-Flusberg H, Cohen DJ, editors. Understanding other minds Perspectives from developmental cognitive neuroscience. 2nd ed. Oxford: Oxford University Press, 2000.
[6] Kanner L. Autistic disturbances of affective contact.Nerv Child 1943;2:217± 50.
[7] Rutter M, Bartak L.Causes of infantile autism:Some considerations from recent research. J Autism Child Schizopr 1971;1:20±33.
[8] American Psychiatric Association.Diagnostical and statistical manual of mental disorders. Washington DC: APA, 1994.
[9] Folstein SE, Santangelo SL, Gilman SE, Piven J, Landa R, Lainhart J, Hein J, Wzorek M. Predictors of cognitive test patterns in autism families. J Child Psychol Psychiatry 1999;40:1117± 28.
[10] Sonuga-Barke EJ.Categorical models of childhood disorder: a conceptual and empirical analysis. J Child Psychol Psychiatry 1998;39:115±33.
[11] Happe F. Autism. London: UCL Press, 1994.
[12] Prior M, Eisenmajer R, Leekham S, Wing L, Gould J,Ong B,Dowe D.Are there subgroups within the autistic spectrum? A cluster analysis of a group of children with autistic spectrum disorders. J Child Psychol Psychiatry 1998; 39: 893 ± 902.
[13] Baron-Cohen S, Leslie AM, Frith U. Does the autistic child have a `theory of mind'. Cognition 1985;21:37±46902.
[14] Happe F, Frith U.The neuropsychology of autism. Brain 1996;119:1377± 400.
[15] Leslie AM. The theory of mind impairment in autism: evidence for a modular mechanism of development? In: Whiten A, editor. Natural theories of mind: Evo-lution, development and simulation of everyday mindreading, Oxford: Basil Blackwell, 1991. p. 63±78.
[16] Baron-Cohen S. Theory of mind and autism: a ®fteen year review. In: Baron-Cohen S, Tager-Flusberg H, Cohen DJ, editors. Understanding other minds Perspectives from developmental cognitive neuroscience, 2nd ed. Oxford: Oxford University Press, 2000. p. 3± 20.
[17] Leslie AM. Pretense and representation in infancy: the origins of `theory of mind'. Psychol Rev 1987;94:84± 106.
[18] Baron-Cohen S. Precursors to a theory of mind: understanding attention in others. In: Whiten A,editor.Natural theories of mind, Oxford: Basil Blackwell, 1991. p. 233± 51.
[19] Boucher J. What could possibly explain autism? In: Carruthers P, Smith PK, editors. Theories of theories of mind, Cambridge: Cambridge University Press, 1996. p. 223±41.
[20] Hobson RP. Autism and the development of mind. UK: Lawrence Erlbaum Associates Ltd, 1993.
[21] Rogers SJ, Pennington BF. A theoretical approach to the de®cits in infantile autism. Dev Psychopathol 1991;3:137±62.
[22] Whiten A. Imitation, pretence and mindreading: secondary representation in comparative primatology and developmental psychology. In:Russon AE, Bard KA, Parker ST,editors.Reaching into thought:The minds of the great apes, Cambridge: Cambridge University Press, 1996. p. 300± 24.
[23] Whiten A. The Machiavellian mindreader. In: Whiten A, Byrne RW, editors. Machiavellian intelligence II: Evaluations and extensions, Cambridge University Press, 1997.
[24] Carruthers P, Smith PK. Introduction. In: Carruthers P, Smith PK, editors. Theories of theories of mind,Cambridge: Cambridge University Press,1996.p.1± 8.
[25] Perner J.Simulation as explicitation of prediction-implicit knowledge about the mind: arguments for a simulation-theory mix. In: Carruthers P, Smith PK, editors. Theories of theories of mind, Cambridge: Cambridge University, 1996. p. 90±104.
[26] Meltzoff A, Gopnik A.The role of imitation in understanding persons and deve- loping a theory of mind. In: Baron-Cohen S, Tager-Flusberg H, Cohen DJ, editors. Understanding other minds, perspectives from autism, Oxford: Oxford University Press, 1993.
[27] Smith IM, Bryson SE. Imitation and action in autism: a critical review. Psychol Bull 1994;116:259±73.
[28] Rogers S. An examination of the imitation de®cit in autism. In: Nadel J, Butterworth G, editors. Imitation in infancy, Cambridge: Cambridge University Press, 1999. p. 255± 83.
[29] Whiten A, Brown J. Imitation and the reading of other minds: perspectives from the study of autism, normal children and non-human primates. In: Braten S, editor. Intersubjective communication and emotion in ontogeny: A sourcebook, Cambridge University Press: Cambridge, 1999. p. 260±80.
[30] Rogers SJ, Bennetto L, McEvoy R, Pennington BF. Imitation and pantomime in high-functioning adolescents with autistic spectrum disorders. Child Dev 1996; 67: 2060± 73.
[31] Hobson RP. Lee AImitation and identi®cation in autism. Journal of Child Psychology and Psychiatry 1999;40:649±60.
[32] DeMeyer MK, Alpern GD, Barton S, DeMyer WE, Churchill DW, Hingtgen JN, Bryson CQ, Pontius W, Kimberlin C. Imitation in autistic, early schizophrenic and non-psychotic subnormal children. J Autism Child Schiz 1972;2:264± 87.
[33] Merians AS, Clark M, Poizner H, Macauley B, Gonzalez-Rothi LJ, Heilman K. Visual-imitative dissociation apraxia. Neuropsychologia 1997; 35: 1483 ± 90.
[34] Goldenberg G, Hagman S. The meaning of meaningless gestures: A study of visuo-imitative apraxia. Neuropsychologia 1997;5:333± 41.
[35] Goldenberg G.Imitating gestures and manipulating a mannikin - the represen- tation of the human body in ideomotor apraxia.Neuropsychologia 1995;33:63± 72.
[36] Melzoff A, Moore MK. Persons and representation: why infant imitation is important for theories of human development. In: Nadel J, Butterworth G, editors. Imitation in infancy, Cambridge University Press, 1999. p. 9± 35.
[37] Perrett DI, Smith PAJ, Potter DD, Mistlin AJ, Head AS,Milner AD, Jeeves MA. Neurons responsive to faces in the temporal cortex: Studies of functional organi-zation, sensitivity to identity and relation to perception. Human Neurobiol 1984; 3: 197± 208.
[38] Perrett DI, Smith PAJ, Mistlin AJ, Chitty AJ,Head AS,Potter DD, Broennimann R, Milner AD, Jeeves MA. Visual analysis of body movements by neurons in the temporal cortex of the macaque monkey: a preliminary report. Behav Brain Res 1985; 16: 153± 70.
[39] Perrett DI, Harries MH, Benson PJ, Chitty AJ, Mistlin AJ.Retrieval of structure from rigid and biological motion; an analysis of the visual response of neurons in the macaque temporal cortex. In: Troscianko T, Blake A, editors. AI and the eye, Chichester: J. Wiley & Sons, 1990. p. 181± 201.
[40] Oram MW, Perrett DI. Responses of anterior superior temporal polysensory (STP) neurons to `biological motion' stimuli. J Cog Neurosci 1994; 6: 99± 116.
[41] Perrett DI, Harries MH, Bevan R, Thomas S, Benson PJ, Mistlin AJ,Chitty AJ, Hietanen J, Ortega JE. Frameworks of analysis for the neural representation of animate objects and actions. J Exp Biol 1989; 146:87 ± 114.
[Tosi vanha piru: Tuo "Pierret" näyttää olevan primus motor; tuollin ei kuitenkaan ole "tiedetty" "peilineuroneista"... vai "onko"? HM]
[42] Perrett DI, Emery NJ. Understanding the intentions of others from visual signals: neurophysiological evidence. Curr Psychol Cog 1994; 13: 683 ± 94.
[43] Emergy NJ, Perrett DI. How can studies of the monkey brain help us under- stand `theory of mind' and autism in humans. In: Baron-Cohen S, Tager-Flusberg H, Cohen DJ,editors.Understanding other minds perspectives from developmental cognitive neuroscience, 2nd ed. Oxford: Oxford University Press, 2000.
[44] Jellema T, Oram MW, Baker CI, Perrett DI. Cell populations in the banks of the superior temporal sulcus of the macaque and imitation. In: Meltzoff A, Prinz W, editors.The imitative mind:development,evolution,and brain bases,2001 (in press).
[45] Jellema T, Baker CI, Wicker B, Perrett DI. Neural representation for the perception of the intentionality of hand actions. Brain Cog 2001; 44: 280 ± 302.
[46] Gallese V, Faddiga L, Fogassi L, Rizzolatti G. Action recognition in the premotor cortex. Brain 1996; 119: 593 ± 609.
[47] Rizzolatti G, Fadiga L, Matelli M, Bettinardi V, Paulesu E, Perani D, Fazio F. Localisation of grasp representations in humans by PETÐ1: observation vs execution. Exp Brain Res 1996; 111: 246 ± 52.
[48] Carey DP. `Monkey see, monkey do' cells. Current Biol 1996; 6:1087 ± 8.
[49] Rizzolatti G, Arbib MA.Language within our grasp. Trends Neurosci 1998; 21: 188 ± 94.
[50] Stevens JA, Fonlupt P,Shiffrar M,Decety J.New aspects of motion perception: selective neural encoding of apparent human movements. Neuroreport 2000; 11: 109 ± 15.
[51] Hari R, Forss N, Avikainen S, Kirveskari E, Salenius S, Rizzolatti G. Acti- vation of human primary motor cortex during action observation: a neuromagnetic study. Proc Natl Acad Sci 1998; 95: 15061 ± 5.
[52] Fadiga L, Fogassi G, Pavesi G, Rizzolatti G. Motor Facilitation during action observation: a magnetic stimulation study. J Neurophysiol 1995; 73: 2608 ± 11.
[53] Grafton ST, Arbib MA, Fagdiga L, Rizzolatti G. Localization of grasp repre-sentations in humans by positron emission tomography 2: observation compared with imagination. Exp Brain Res 1996; 112: 103 ± 11.
[54] Rizzolatti G, Fadiga L, Gallese V, Fogassi L. Premotor cortex and the
recognition of motor actions. Cog Brain Res 1996; 3: 131 ± 41.
[55] Iacoboni M, Woods RP, Brass M, Bekkering H, Mazziota JC, Rizzolatti G. Cortical mechanisms of human imitation. Science 1999; 286: 2526 ± 8.
[56] Fogassi L, Gallese V, Fadiga L, Rizzolatti G. Neurons responding to the sight of goal-directed hand/arm actions in the parietal area PF (7b) of the macaque monkey. Soc Neurosci Abstracts 1998; 257(5): 654.
[57] Liberman AM, Cooper F, Shankweiler M, Studdert-Kennedy M. Perception of the speech code. Psychol Rev 1967; 74: 431 ± 61.
[58] Liberman AM, Whalen DH. On the relation of speech to language. Trends in Cognitive Sciences 2000;4:187± 96.
[59] Gallese V, Goldman A. Mirror neurons and the simulation theory of mind-reading. Trends Cog Sci 1998;2:493±501.
[60] Gallese V. Agency and motor representations: new perspectives on intersub-jectivity. ISC working papers 2000-6. Workshop on Autism and the Theory of Mind, Lyon, 18th May, 2000. http://www.isc.cnrs.fr/wp/wp00-6.htm.
[61] Hat®eld E, Caciopoo JT, Rapson RL. Emotional contagion. New York: Cambridge University Press, 1994.
[62] Surakka V, Hietanen JK. Facial and emotional reactions to Duchenne and non-Duchenne smiles. Int J Psychophysiol 1998; 29: 23 ± 33.
[63] Baron-Cohen S. Mindblindness: An essay on autism and theory of mind. Cambridge, MA: Bradford Books, MIT Press, 1995.
[64] Baron-Cohen S, Cox A, Baird G, Swettenham J, Nightingale N, Morgan K, Drew A, Charman T. Psychological markers in the detection of autism in infancy in a large population. Brit J Psychiat 1996; 168: 158 ± 63.
[65] Visalberghi E, Fragaszy D. Do monkeys ape? In: Parker S, Gibson K, editors. Language and intelligence in monkeys and apes: Comparative developmental perspectives, Cambridge, UK: Cambridge University Press, 1990. p. 247± 73.
[66] Whiten A, Ham R. On the nature and evolution of imitation in the animal king-dom:Reappraisal of a century of research.Advance Study Behav 1992;21:239±83.
[67] Whiten A. Primate culture and social learning. Cog Sci 2000; 24: 477 ± 508.
[68] Hughes C, Russell J, Robbins TW. Evidence for executive dysfunction in autism. Neuropsychologia 1994;32:477±92.
[69] Hughes C. Planning problems in autism at the level of motor control. J Autism Dev Disord 1996; 26: 99± 107.
[70] Ozonoff S, Pennington B, Rogers SJ. Executive function deficits in highfunc-tioning autistic individuals: relationship to theory of mind. J Child Psychol Psychiatry 1991; 32: 1081 ± 105.
[71] Ozanoff S, Jensen J. Specific executive function profiles in three
neurodevelopmental disorders. J Autism Dev Disord 1999; 29:171±7.
[72] Pennington BF, Ozonoff S. Executive Functions and Developmental
Psychopathology. J Child Psychol Psychiatry 1996; 37: 51 ± 87.
[73] Byrne RW, Russon AE. Learning by imitation: a hierarchical approach. Behav Brain Sci 1998; 21: 667 ± 721.
[74] Whiten A. Imitation of sequential and hierarchical structure in action: experi- mental studies with children and chimpanzees. Proceedings of the AISB Conven-tion, Symposium on Imitation in Animals and Artefacts,Edinburgh,1999.p. 38 ± 46.
[75] Byrne RW. Imitation without intentionality. Using string parsing to copy the organization of behaviour. Animal Cognition 1999; 2: 63 ± 72.
[76] Perner J, Lang B. Development of theory of mind and executive control. Trends Cog Sci 1999; 3: 337 ± 44.
[77] Griffith EM, Pennington B, Wehner EA, Rogers SJ. Executive functions in young children with autism. Child Development 1999; 70(4): 817 ± 32.
[78] Ozanoff S, Strayer DL.Inhibitory function in non-retarded children with autism. J Autism Dev Disord 1997; 27(1): 59 ± 77.
[79] Hughes C, Leboyer M, Bouvard M. Executive function in parents of children with autism. Psychological Medicine 1997; 27: 209 ± 20.
[80] Klein SB, Chan RL, Loftus J. Independence of episodic and semantic self-knowledge: the case from autism. Soc Cog 1999; 17: 413 ± 36.
[81] Suddendorf, T. Discovery of the fourth dimension: mental time travel and human evolution. Master's thesis, University of Waikato, Hamilton, New Zealand, 1994. Internet: http://cogprints.soton.ac.uk.
[82] Suddendorf T,Corballis MC.Mental time travel and the evolution of the human mind. Genetic, Social, and General Psychology Monographs 1997; 123: 133 ± 67.
[83] Suddendorf T. The rise of the metamind. In: Corballis MC, Lea CS, editors. The descent of mind, Oxford: Oxford University Press, 1999. p. 218 ± 60.
[84] Nakamura K, Kawashima R, Ito K, Sugiura M, Kato T,Nakamura A, Hatano K, Nagumo S, Kubota K, Fukuda H, Kijima S. Activation of the right inferior frontal cortex during assessment of facial emotion. J Neurophysiol 1999;82:1610±4.
[85] Baron-Cohen S, Ring HA, Wheelwright S, Bullmore ET, Brammer MJ, Simmons A, Williams CR. Social intelligence in the normal and autistic brain: an fMRI study. Eur J Neurosci 1999; 11: 1891 ± 8.
[86] Frith U, Frith C. The physiological basis of theory of mind: functional neuro-imaging studies. In: Baron-Cohen S, Tager-Flusberg H, Cohen DJ, editors. Under-standing other mindsÐPerspectives from developmental cognitive neuroscience, 2nd ed. Oxford: Oxford University Press, 2000.
[87] Charman T, Baron-Cohen S. Another Look at Imitation in Autism. Dev Psychopathol 1994; 6: 403 ± 13.
[88] McGurk H, MacDonald JW.Hearing lips and seeing voices. Nature 1976; 264: 746 ± 8.
[89] Avikainen S, Kulomaki T, Hari R. Normal movement reading in Asperger subjects. Neuroreport 1999; 10: 3467 ± 70.
[90] Whiten A,Byrne RW.Machiavellian intelligence II:Evaluations and extensions. Cambridge University Press, 1997.

 

 

 

 

Sari Avikainen nojaa tähän aivopieruun väitöskirjassaan 2005:

 

http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/avikainen/cortical.pdf

 

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6.1.4 Functional role of the MNS

MNS function is based, according to the direct-matching hypothesis (Rizzolatti et al. 2001), on mapping of the visual representation of an action onto the observer’s own motor representation of the same action. This matching function has been suggested to be in involved in different behaviors, such as action understanding, imitation, attributing mental states, and even in some aspects of language. In action understanding, the motor knowledge of the observer is used for understan-ding and recognizing actions of others (Rizzolatti et al. 2001). In line with this as-sumption, in a PET study by Grezes et al. (1998) the premotor areas were stron-ger activated during observation of meaningful arm actions, when the subjects had to undertand the purpose of the actions than when they just had to imitate the actions.

The term imitation can be used to describe many kind of functions in biology, sociology and psychology. When simple defined as copying by an observer of an action performed by a model, the underlying neural mechanism has been pro-posed to be based on the MNS (Iacoboni et al. 1999; Nishitani and Hari 2000; Rizzolatti et al. 2001; Nishitani and Hari 2002; Wohlschläger and Bekkering 2002). The function of the MNS may involve different imitative phenomena, such as ‘res-ponse facilitation’ (an automatic tendency to reproduce observed movements) in-cluding release phenomena in birds and yawning, laughing and neonatal imitation in humans (Meltzoff and Moore 1977), further to higher order imitation and imitative learning (Rizzolatti et al. 2001; Wohlschläger and Bekkering 2002).

The possible role of the MNS in other complex cognitive functions, such as lan-guage (Rizzolatti and Arbib 1998) and mind-reading (Gallese and Goldman 1998), has also been discussed.In line with the motor theory of speech perception (Liber- man and Mattingly 1985; Liberman and Whalen 2000), suggesting that successful linguistic communication is not dependent on sound, but rather on a neural link between the sender and the receiver that allows production of phonetic gestures, Rizzolatti and Arbib (1998) proposed that the action execution/observation mat-ching system could have served as the neural prequisite for the development of interindividual communication and finally speech. Interestingly, in a recent study by Petitto et al. (2001), babies with profoundly deaf parents were shown to convey a kind of silent linguistic babling with their hand movements.

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Gallese and Goldman (1998) have proposed that the ability to detect and recog-nize mental states of others could have evolved from the MNS. According to one of the dominant mind-reading theories, the simulation theory (Davies and Stone 1995), other person’s mental states are detected by matching their states with resonant states of one’s own. Shared representations of different actions could serve as the basis of getting the observer into the same ‘mental shoes’ as the target (Gallese and Goldman 1998).

According to the simulation theory, all mental states requiring TOM, irrespective of whether they are are attributed to others or to oneself, should involve same neuro-nal system. However, in a fMRI study by Vogeley et al.(2001), modeling ones own mental-states activated at least in part dintinct brain regions than modeling the mental-states of others, opposed to the basic idea of simulation.

Although the relation of the MNS to different cognitive functions is still merely spe-culative, the discovery of the mirror neurons has offered a new tool to investigate brain function in our social enviroment. Future goals in this field include mapping of all brain areas involved in the mirror-neuron system and obtaining more infor-mation about their precise role in it. Futhermore,more information is needed about different stimulus types and modalities that are able to evoke mirror-neuron type activation, about the connection of the mirror-neuron system with different cogni-tive capacities, and about the possible role of a dysfunctional mirror-neuron system in different patient groups.

6.2 Autism

The autism spectrum disorders are a group of neurodevelopmental disorders that have a great variability in their clinical presentation but alltogether share some core symptoms, such as social impairment, deficits in communication, and restric-tive pattern of behaviour. Autism has been a great challenge for neuroscience during the last decade.

Although a lot has been learned since the time when it was thought to be a psy-chogenic syndrome caused by “refrigerator mothers”, the rapidly growing body of literature reports very heterogenous findings and theories about the basis of autism.

Abnormalities have been observed in many brain regions. However, not all sub-jects with autism show any abnormalities e.g. in structural or functional brain ima-ging, and none of the found abnormalities characterizes all subjects.In spite of the intensive research, we still don’t know whether autism is a single syndrome vary-ing in severity or whether the autism spectrum of disorders have multiple etiologies that nonetheless lead into similar core symptoms.

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Autism is a rather common syndrome affecting about 0.7% of the general popu-lation of children and adolescents (Gillberg and Wing 1999). Since it is a lifelong disorder with severe deficits in social interaction and communication and since many of the subjects have psychiatric and neurologic comorbidities, there is a great need for long-term institutional, medical, educational and psycho-social care. The costs for the individuals, the families and the society are significant. Even subjects at the able end of the disorder often have problems in coping in-dependently due to the social deficits that make their every-day life difficult. Sofar the treatment in autism merely includes rehabilitation and symptomatic medi-cation, no curative treatment exists. Although these means can of course relieve comorbid symptoms and help the subjects and families to manage in every-day life, there is evidence (Gillberg and Billstedt 2000) that the core features of autism do not change much over time. On the other hand, most of the intensive rehabili-tation has only been performed during the last decade, and randomised follow-up studies of these interventios are merely lacking. Most effective results have sofar been obtained from early and highly intensive intervention programmes (Howlin et al. 1995).

6.2.1 Autism and mirror neurons

None of the cognitive theories of autism (such TOM, weak central coherence and executive function deficit) has proven to be exclusive and none has been able to explain the whole range of symptoms found in autism. Most theories focus on so-cial symptoms, since in spite of the wide clinical variation all subjects with autism spectrum disorders suffer from social deficits. However, the neural basis of the deficit is largely unknown.

The discovery of mirror neurons has lead to hypothesis of their role in social cog-nition (Gallese and Goldman 1998; Rizzolatti et al.2001; Williams et al.2001). Es-pecially, when evidence of the human counterpart of the monkey mirror neurons was found, a question of the possible dysfunction of the MNS in conditions associ-ated with social impairments, such as autism, was raised. Dysfunction of the MNS could lead in impairments in imitation, action understanding and further in difficul-ties in using and understanding body-language, mentalising, joint attention and even some aspects of language (Williams et al. 2001).

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Total dysfunction, partial dysfunction, a dysfunction in certain parts of the MNS, or a developmental delay could all be in question.

In Studies II, V, and VI the hypothesis of possible connection between MNS and autism was tested. Study II showed rather normal activation of the primary motor cortex in a group of AS subjects both during observation and execution of manipu-lative hand actions, in spite of the deficit in their TOM abilities. The results exluded the possibility of a total dysfunction of the MNS in Asperger subjects.Furthermore, no evidence was found of the connection between a TOM deficit and MNS dys-function. However, the number of subjects was small (N = 5) and although no sta-tistically significant differences were observed, a slight tendency was evident toward a weaker activation of the M1 in AS subjects.

In Study V, the AS and HFA subjects’ imitation abilities were examined by using a behavioural task. Recent evidence suggests that human imitation is based on the mirror-neuron system (Iacoboni et al. 1999; Nishitani and Hari 2000; Wohlschläger and Bekkering 2002). Normally people tend to imitate as in looking at a mirror (Bekkering et al. 2000; Iacoboni et al. 2001) and observation of movements in a mirror-image view speeds up performance also in non-imitative tasks (Brass et al. 2000; Brass et al. 2001).

However, Study V showed that AS and HFA subjects are impaired in goal-direc-ted imitation, when the imitation occurs in a mirror-image fashion. As certain as-pects of imitation, such as imitation requiring self-other visual transformations, are most susceptible for MNS function (Williams et al. 2001), a developmental delay or adysfunction of the MNS could explain the observed results.

In Study VI, the hypothesis of a MNS dysfunction in autism was tested further by recording cortical activations while AS subjects imitated orofacial gestures. The results showed abnormal activation in the IF and M1 areas. As the the human mirror-neuron areas (the inferior parietal region, the Broca’s region and the M1) are activated in sequence, dysfunction of both frontal and parietal part of the MNS could explain the delayed and weaker activation of the IF and M1 areas. Broca’s region, the homologue of monkey F5 area, is activated during observation, exe-cution and imitation of hand and mouth movements (Iacoboni et al.1999; Nishitani and Hari 2000; Nishitani and Hari 2002) and considered as an essential part of the human MNS. Dysfunction of the IF part of the MNS could affect social abilities via connections to the orbitofrontal cortex and to the anterior ventral medial frontal region that are considered to contribute to theory of mind.

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The STS region is closely connected to the MNS function and it has an important role in perception of many kind of socially relevant visual stimuli (for a review, see Allison et al. 2000; Puce and Perrett 2003). Interestigly, the STS region is also ac-tivated in tasks requiring mentalising (McGuire et al. 1996; Gallagher et al. 2000). In line with these results, autistic children, have been shown to be impaired in vi-sual recognition of biological motion (Blake et al. 2003). In a PET study by Castelli et al. (2000), activations of the STS and medial prefrontal cortex were weaker in autistic than in control subjects during a mentalising task, whereas the activity of the exstrastriate cortices did not differ from the controls. However, in Study VI ac-tivation of the occipital and STS areas did not differ between AS and control sub-jects. This discrepancy probably reflects different activation cascades within the STS region; perception of an mouth and hand actions in order to imitate might be intact in the STS level in AS subjects, whereas processing of more abstract and complex social stimuli (such as cartoons and stories of TOM) could be affected. Accordingly, perception of goal-directed hand actions was found to activate the caudal STS and the intraparietal sulcus, whereas perception of expressive whole-body motion activated the rostrocaudal STS, as well as the limbic structures, including the amygdala (Bonda et al. 1996).

Subjects in Studies II, V, and VI were adults and had AS (except one subject in Study II and two subjects in Study V who were autistic) representing the able end of the autism spectrum disorders. This subject group was chosen, since MEG re-cordings require some co-operation from the subjects, especially when tasks in-volve active participation. Additionally, the subjects have to keep their heads stea-dy during the measurement to avoid movement artefacts and to enable identifi-cation of accurate source locations. Futhermore, in the AS group the amount of other factors that could affect the results, such as medication, comorbidities and language problems, is at minimum. Adult subjects were studied, because the knowledge of MEG responses in children and adolescents is still rather limited. However, in adults with the most “mildest” form of the disorder, the size of the effect could be smaller than in more severely affected subjects. On the other hand, although most AS and high-functioning autistic subjects, are of normal intelligence, they suffer from social difficulties, which according to the MNS hypothesis are just the symptoms that are linked with the MNS function.

Altogether, the results from Studies II and VI suggest that MNS dysfunction can account for a part of the imitation and social impairments in subjects with Asperger’s syndrome.

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Since we only studied able adult subjects, it would be interesting in the future to examine MNS function in more affected and younger subjects. Furthermore, modulatory influences from the prefrontal theory-of-mind regions on the MNS should be evaluated.

In autism research, lack of replication of studies, small and heterogenous experi-mental groups and poor control of other confounding variables have for long been a problem, therefore future studies should attempt to investigate more homoge-neous subgroups within the autism spectrum disorders. Effective communication between reseachers on this field will help to integrate and update the diagnostic criteria for the different subgroups. The studies should also aim at integrating in-formation from different fields of the research, such as genetics, functional ima-ging and neuropsychology. Hopefully, in the near future we are able to understand much better the biological mechanisms underlying the mystery of autism.

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9. REFERENCES

Abell, F., Krams, M., Ashburner, J., Passingham, R., Friston, K., Frackowiak, R., Happe, F., Frith, C., and Frith, U. 1999. The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans. Neuroreport, 10:1647-1651.

Adolphs, R. 1999. Social cognition and the human brain. Trends Cogn Sci, 3:4699. REFERENCES-479.

Adolphs, R. 2003. Cognitive neuroscience of human social behaviour. Nat Rev Neurosci 4:165-178.

Adolphs, R., Tranel, D., Damasio, H., and Damasio, A.R. 1995. Fear and the human amygdala. J. Neurosci 15:5879-5891.

Adolphs, R., Tranel, D., and Damasio, A.R. 1998. The human amygdala in social judgment. Nature 393: 470-474.

Adolphs, R., Sears, L., and Piven, J. 2001. Abnormal processing of social information from faces in autism. J Cogn Neurosci 13:232-240.

Adrian, E.D. 1944. Brain rhythms. Nature 153:360-362.

Ahonen, A.I., Hämäläinen, M.S., Kajola, M.J., Knuutila, J.E.T., Laine, P.P., Lounasmaa, O.V., Parkkonen, L.T., Simola, J.T., and Tesche, C.D. 1993. 122-channel SQUID instrument for investigating the magnetic signals from the human brain. Physica Scripta T49:198-205.

Allison, T., McCarthy, G., Wood, C.C., Darcey, T.M., Spencer, D.D., and Williamson, P.D. 1989. Human cortical potentials evoked by stimulation of the median nerve. II. Cytoarchitectonic areas generating short-latency activity. J Neurophysiol 62:694-710.

Allison, T., McCarthy, G., Wood, C.C., and Jones, S.J. 1991. Potentials evoked in human and monkey cerebral cortex by stimulation of the median nerve. A review of scalp and intracranial recordings. Brain 114:2465-2503.

Allison, T., McCarthy, G., Nobre, A., Puce, A., and Belger, A. 1994. Human extrastriate visual cortex and the perception of faces, words, numbers, and colors. Cereb Cortex 4:544-554.

Allison, T., Puce, A., Spencer, D.D., and McCarthy, G. 1999. Electrophysiological studies of human face perception. I: Potentials generated in occipitotemporal cortex by face and non-face stimuli. Cereb Cortex 9:415-430.

Allison, T., Puce, A., and McCarthy, G. 2000. Social perception from visual cues: role of the STS region. Trends Cogn Sci 4:267-278.

Amaral, D.G., and Insausti, R. 1992. Retrograde transport of D-[3H]-aspartate injected into the monkey amygdaloid complex. Exp Brain Res 88:375-388.

Amir, R.E., Van den Veyver, I.B., Wan, M., Tran, C.Q., Francke, U., and Zoghbi, H.Y. 1999. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23: 185 - 188.

Anderson, A.K., and Phelps, E.A. 2001. Lesions of the human amygdala impair enhanced perception of emotionally salient events. Nature 411:305-309.

Asperger, H. 1944. Die autistischen Psychopathen im Kindealter. Archiv fur Psychiatrie und Nervenkrankheiten 117:76-136.

71

Aylward, E.H., Minshew, N.J., Goldstein, G., Honeycutt, N.A., Augustine, A.M., Yates, K.O., Barta,P.E., and Pearlson, G.D. 1999. MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults. Neurology 53:2145-2150.

Bailey, A., Luthert, P., Bolton, P., Le Couteur, A., Rutter, M., and Harding, B. 1993. Autism and megalencephaly. Lancet 341:1225-1226.

Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., and Rutter, M. 1995. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 25:63-77.

Bailey, A., Luthert, P., Dean, A., Harding, B., Janota, I., Montgomery, M., Rutter, M., and Lantos, P. 1998. A clinicopathological study of autism. Brain 121:889-905.

Barbas, H. 1988. Anatomic organization of basoventral and mediodorsal visual recipient prefrontal regions in the rhesus monkey. J Comp Neurol 276:313-342.

Baron-Cohen, S. 1988. Social and pragmatic deficits in autism: cognitive or affective? J Autism Dev Disord 18:379-402.

Baron-Cohen, S. 1989. The autistic child's theory of mind: a case of specific developmental delay. J Child Psychol Psychiatry 30:285-297.

Baron-Cohen, S., Leslie, A.M., and Frith, U. 1985. Does the autistic child have a "theory of mind"? Cognition 21:37-46.

Baron-Cohen, S., Ring, H., Moriarty, J., Schmitz, B., Costa, D., and Ell, P. 1994. Recognition of mental state terms. Clinical findings in children with autism and a functional neuroimaging study of normal adults. Br J Psychiatry 165:640-649.

Baron-Cohen, S., Jolliffe, T., Mortimore, C., and Robertson, M. 1997a. Another advanced test of theory of mind: evidence from very high functioning adults with autism or asperger syndrome. J Child Psychol Psychiatry 38:813-822.

Baron-Cohen, S., Wheelwright, S., and Jolliffe, T. 1997b. Is there a 'language' of the eyes? Evidence from normal adults, and adults with autism or Asperger's syndrome. Visual Cogn 4:311-331.

Baron-Cohen, S., Ring, H.A., Wheelwright, S., Bullmore, E.T., Brammer, M.J., Simmons, A., and Williams, S.C. 1999. Social intelligence in the normal and autistic brain: an fMRI study. Eur J Neurosci 11: 1891 - 1898.

Bauman, M., and Kemper, T.L. 1985. Histoanatomic observations of the brain in early infantile autism. Neurology 35:866-874.

Baumgartner, C., Sutherling, W.W., Di, S., and Barth, D.S. 1991. Spatiotemporal modeling of cerebral evoked magnetic fields to median nerve stimulation. Electroencephalogr Clin Neurophysiol 79:27-35.

Bekkering, H., Wohlschlager, A., and Gattis, M. 2000. Imitation of gestures in children is goal-directed. Q J Exp Psychol A 53:153-164.

Berger, H. 1929. Uber das Elektroenkephalogramm des Menchen. Arch Psychiatr Nervenkr 87:527-570.

Berlucchi, G., and Aglioti, S. 1997. The body in the brain: neural bases of corporeal awareness. Trends Neurosci 20:560-564.

Blake, R., Turner, L.M., Smoski, M.J., Pozdol, S.L., and Stone, W.L. 2003. Visual recognition of biological motion is impaired in children with autism. Psychol Sci 14:151-157.

Bonda, E., Petrides, M., Ostry, D., and Evans, A. 1996. Specific involvement of human parietal systems and the amygdala in the perception of biological motion. J Neurosci 16:3737-3744.

Bowler, D.M. 1992. "Theory of mind" in Asperger's syndrome. J Child Psychol Psychiatry 33:877-893.

72

Brass, M., Bekkering, H., Wohlschlager, A., and Prinz, W. 2000. Compatibility between observed and executed finger movements: comparing symbolic, spatial, and imitative cues. Brain Cogn 44:124-143.

Brass, M., Bekkering, H., and Prinz, W. 2001. Movement observation affects movement execution in a simple response task. Acta Psychol (Amst) 106:3-22.

Breiter, H.C., Etcoff, N.L., Whalen, P.J., Kennedy, W.A., Rauch, S.L., Buckner, R.L., Strauss, M.M., Hyman, S.E., and Rosen, B.R. 1996. Response and habituation of the human amygdala during visual processing of facial expression. Neuron 17:875-887.

Brothers, L., Ring, B., and Kling, A. 1990. Response of neurons in the macaque amygdala to complex social stimuli. Behav Brain Res 41:199-213.

Brunet, E., Sarfati, Y., Hardy-Bayle, M.C., and Decety, J. 2000. A PET investigation of the attribution of intentions with a nonverbal task. Neuroimage 11:157-166.

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.

Burgoine, E., and Wing, L. 1983. Identical triplets with Asperger's syndrome. Br J Psychiatry 143:261-265.

Burton, H. 1986. Second somatosensory cortex and related areas. In Cerebral Cortex (E.G. Jones, A. Peters, Eds.), pp. 31-98. Plenum.

Burton, H., and Robinson, C.J. 1987. Responses in the first and second somatosensory cortical area in cats during transient inactivation of the other ipsilateral area with lidocain hydrochloride. Somatosens Res 4:215-236.

Burton, H., Sathian, K., and Shao, D.H. 1990. Altered responses to cutaneous stimuli in the second somatosensory cortex following lesions of the postcentral gyrus in infant and juvenile macaques. J Comp Neurol 291:395-414.

Burton, H., Sinclair, R.J., Hong, S.Y., Pruett, J.R., Jr., and Whang, K.C. 1997. Tactile-spatial and cross-modal attention effects in the second somatosensory and 7b cortical areas of rhesus monkeys. Somatosens Mot Res 14:237-267.

Cahill, L., Haier, R.J., Fallon, J., Alkire, M.T., Tang, C., Keator, D., Wu, J., and McGaugh, J.L. 1996. Amygdala activity at encoding correlated with long-term, free recall of emotional information. Proc Natl Acad Sci USA 93:8016-8021.

Calder, A.J., Lawrence, A.D., Keane, J., Scott, S.K., Owen, A.M., Christoffels, I., and Young, A.W. 2002. Reading the mind from eye gaze. Neuropsychologia 40:1129-1138.

Carlsson, K., Petrovic, P., Skare, S., Petersson, K.M., and Ingvar, M. 2000. Tickling expectations: neural processing in anticipation of a sensory stimulus. J Cogn Neurosci 12:691-703.

Carper, R.A., Moses, P., Tigue, Z.D., and Courchesne, E. 2002. Cerebral lobes in autism: early hyperplasia and abnormal age effects. Neuroimage 16:1038-1051.

Caselli, R.J. 1993. Ventrolateral and dorsomedial somatosensory association cortex damage produces distinct somesthetic syndromes in humans. Neurology 43:762-771.

Castelli, F., Happe, F., Frith, U., and Frith, C. 2000. Movement and mind: a functional imaging study of perception and interpretation of complex intentional movement patterns. Neuroimage 12:314-325.

Cavada, C., and Goldman-Rakic, P.S. 1989. Posterior parietal cortex in rhesus monkey: II. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe. J Comp Neurol 287:422-445.

73

Chapman, R.M., Ilmoniemi, R., Barbanera, S., and Romani, G.L. 1984. Selective localization of the alpha brain activity with neuromagnetic measurements. Electroencephalogr Clin Neurophysiol 58:569-572.

Charman, T., Swettenham, J., Baron-Cohen, S., Cox, A., Baird, G., and Drew, A. 1997. Infants with autism: an investigation of empathy, pretend play, joint attention, and imitation. Dev Psychol 33:781-789.

Chatrian, G.E., Petersen, M.C., and Lazarte, J.A. 1959. The blocking of the rolandic wicket rhtyhm and some central changes related to movement. Electroencephalogr Clin Neurophysiol 11:497–510.

Cheron, G., and Borenstein, S. 1987. Specific gating of the early somatosensory evoked potentials during active movement. Electroencephalogr Clin Neurophysiol 67:537-548.

Cohen, L.G., and Starr, A. 1987. Localization, timing and specificity of gating of somatosensory evoked potentials during active movement in man. Brain 110 (Pt 2):451-467.

Conway, B.A., Halliday, D.M., Farmer, S.F., Shahani, U., Maas, P., Weir, A.I., and Rosenberg, J.R. 1995. Synchronization between motor cortex and spinal motoneuronal pool during the performance of a maintained motor task in man. J Physiol 489:917-924.

Cook, E.H., Jr. 2001. Genetics of autism. Child Adolesc Psychiatr Clin N Am 10:333-350.

Corkum, V., and Moore, C. 1998. The origins of joint visual attention in infants. Dev Psychol 34:28-38.

Courchesne, E., Yeung-Courchesne, R., Press, G.A., Hesselink, J.R., and Jernigan, T.L. 1988. Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med 318:1349-1354.

Curcio, F., and Piserchia, E.A. 1978. Pantomimic representation in psychotic children. J Autism Child Schizophr 8:181-189.

Damasio, A.R. 1996. The somatic marker hypothesis and the possible functions of the prefrontal cortex. Philos Trans R Soc Lond B Biol Sci 351:1413-1420.

Damasio, A.R., and Maurer, R.G. 1978. A neurological model for childhood autism. Arch Neurol 35:777- 786.

Davidovitch, M., Patterson, B., and Gartside, P. 1996. Head circumference measurements in children with autism. J Child Neurol 11:389-393.

Davies, M., and Stone, T. 1995. Mental Simulation Blackwell.

DeMeyer, M.K., Alpern, G.D., Barton, S., DeMyer, W.E., Churchill, D.W., Hingtgen, J.N., Bryson, C.Q., Pontius, W., and Kimberlin, C. 1972. Imitation in autistic, early schizophrenic, and non-psychotic subnormal children. J Autism Child Schizophr 2:264-287.

di Pellegrino, G., Fadiga, L., Fogassi, L., Gallese, V., and Rizzolatti, G. 1992. Understanding motomevents: a neurophysiological study. Exp Brain Res 91:176-180.

Egaas, B., Courchesne, E., and Saitoh, O. 1995. Reduced size of corpus callosum in autism. Arch Neurol 52:794-801.

Ehlers, S., and Gillberg, C. 1993. The epidemiology of Asperger syndrome. A total population study. J Child Psychol Psychiatry 34:1327-1350.

Ehlers, S., Nyden, A., Gillberg, C., Sandberg, A.D., Dahlgren, S.O., Hjelmquist, E., and Oden, A. 1997. Asperger syndrome, autism and attention disorders: a comparative study of the cognitive profiles of 120 children. J Child Psychol Psychiatry 38:207-217.

74 Ellis, H.D., and Gunter, H.L. 1999. Asperger syndrome: a simple matter of white matter? Trends Cogn Sci 3:192-200.

Escalona, A., Field, T., Nadel, J., and Lundy, B. 2002. Brief report: imitation effects on children with autism. J Autism Dev Disord 32:141-144.

Fabri, M., Polonara, G., Quattrini, A., Salvolini, U., Del Pesce, M., and Manzoni, T. 1999. Role of the corpus callosum in the somatosensory activation of the ipsilateral cerebral cortex: an fMRI study of callosotomized patients. Eur J Neurosci 11:3983-3994.

Fadiga, L., Fogassi, L., Pavesi, G., and Rizzolatti, G. 1995. Motor facilitation during action observation: A magnetic stimulation study. J Neurophysiol 73:2608-2611.

Ferrari, P., F., Gallese, V., Rizzolatti, G., and Fogassi, L. 2003. Mirror neurons responding to the observation of ingestive and communicative mouth actions in the monkey ventral premotor cortex.Eur J Neurosci 17: 1703-1714.

Field, T., Sanders, C., and Nadel, J. 2001. Children with autism display more social behaviors after repeated imitation sessions. Autism 5:317-323.

Fine, C., Lumsden, J., and Blair, R.J. 2001. Dissociation between 'theory of mind' and executive functions in a patient with early left amygdala damage. Brain 124:287-298.

Fletcher, P.C., Happe, F., Frith, U., Baker, S.C., Dolan, R.J., Frackowiak, R.S., and Frith, C.D. 1995. Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension. Cognition 57:109-128.

Flor, H., Mühlnickel, W., Karl, A., Denke, C., Grüsser, S., and Taub, E. 1998. A neural substrate for nonpainful phantom limb phenomena. Society for Neuroscience Abstracts 24:249.16.

Fogassi, L., Gallese, V., Fadiga, L., and Rizzolatti, G. 1998. Neurons responding to the sight of goal directed hand/arm actions in the parital area PF (7b) of the macaque monkey. Soc Neurosci abstr 24:257.5.

Forss, N., and Jousmäki, V. 1998. Sensorimotor integration in human primary and secondary somatosensory cortices. Brain Res 781:259-267.

Forss, N., Hari, R., Salmelin, R., Ahonen, A., Hämäläinen, M., Kajola, M., Knuutila, J., and Simola, J. 1994a. Activation of the human posterior parietal cortex by median nerve stimulation. Exp Brain Res 99:309-315.

Forss, N., Salmelin, R., and Hari, R. 1994b. Comparison of somatosensory evoked fields to airpuff and electric stimuli. Electroencephalogr Clin Neurophysiol 92:510-517.

Forss, N., Merlet, I., Vanni, S., Hämäläinen, M., Mauguiere, F., and Hari, R. 1996. Activation of human mesial cortex during somatosensory target detection task. Brain Res 734:229-235.

Forss, N., Hietanen, M., Salonen, O., and Hari, R. 1999. Modified activation of somatosensory cortical network in patients with right-hemisphere stroke.  Brain 122:1889-1899.

Friesen, C.K., and Kingstone, A. 1998. The eyes have it!:reflexive orienting is triggered by nonpredictive gaze. Psychonomic Bull Rev 5:

Frith, U., and Happe, F. 1994. Autism: beyond "theory of mind". Cognition 50:115-132.

Frith, U., Morton, J., and Leslie, A.M. 1991. The cognitive basis of a biological disorder: autism. Trends Neurosci 14:433-438.

Frot, M., and Mauguiere, F. 1999. Timing and spatial distribution of somatosensory responses recorded in the upper bank of the sylvian fissure (SII area) in humans. Cereb Cortex 9:854-863.

75

Galea, M.P., and Darian-Smith, I. 1994. Multiple corticospinal neuron populations in the macaque monkey are specified by their unique cortical origins, spinal terminations, and connections. Cereb Cortex 4:166-194.

Gallagher, H.L., Happe, F., Brunswick, N., Fletcher, P.C., Frith, U., and Frith, C.D. 2000. Reading the mind in cartoons and stories: an fMRI study of 'theory of mind' in verbal and nonverbal tasks. Neuropsychologia 38:11-21.

Gallese, V., and Goldman, A. 1998. Miror neurons and the simulation theory of mind-reading. Trends Cogn Sci 2:493-501.

Gallese, V., Fadiga, L., Fogassi, L., and Rizzolatti, G. 1996. Action recognition in the premotor cortex. Brain 119:593-609.

Gallese, V., Fogassi, L., Fadiga, L., and Rizzolatti, G. 2002. Action representation and the inferior parietal lobule. In Attention and Performance (W. Prinz, B. Hommel, Eds.), pp. 334-355. Oxford University Press, Oxford.

Garcia-Larrea, L., Bastuji, H., and Mauguiere, F. 1991. Mapping study of somatosensory evoked potentials during selective spatial attention. Electroencephalogr Clin Neurophysiol 80:201-214.

Gastaut, H. 1952. Etude electrocorticographique de la reactivite des rytmes rolandiques. Revue de Neurologie (Paris) 87:176-182.

Gattis, M., Bekkering, H., and Wohlschläger, A. 2002. Goal-directed imitation. In The Imitative Mind (A. Meltzoff, W. Prinz, Eds.), pp. 183-205. Cambridge University Press, Cambridge.

Geday, J., Gjedde, A., Boldsen, A.S., and Kupers, R. 2003. Emotional valence modulates activity in the posterior fusiform gyrus and inferior medial prefrontal cortex in social perception. Neuroimage 18:675-684.

Ghez, C. 1991. Voluntary movement. In Principles of Neural Science (E. Kandel, J.H. Schwartz, T.M. Jessell, Eds.), pp. 609-625. Prentice-Hall International Inc.

Gillberg, C. 1991. Outcome in autism and autistic-like conditions. J Am Acad Child Adolesc Psychiatry 30:375-382.

Gillberg, C. 1995. The prevalence of autism and autism spectrum disorders. In The Epidemiology of Child and Adolescent Psychopathology (F.C. Verhulst, H.M. Koot, Eds.), pp. 227-257. Oxford University Press, Oxford.

Gillberg, C. 1998. Asperger syndrome and high-functioning autism. Br J Psychiatry 172:200-9.

Gillberg, C., and Wing, L. 1999. Autism: not an extremely rare disorder. Acta Psychiatr Scand 99:399- 406.

Gillberg, C., and Billstedt, E. 2000. Autism and Asperger syndrome: coexistence with other clinical disorders. Acta Psychiatr Scand 102:321-330.

Gillberg, I.C., and Gillberg, C. 1989. Asperger syndrome-some epidemiological considerations: a research note. J Child Psychol Psychiatry 30:631-638.

Goel, V., Grafman, J., Sadato, N., and Hallett, M. 1995. Modeling other minds. Neuroreport 6:1741- 1746.

Grafton, S.T., Arbib, M.A., Fadiga, L., and Rizzolatti, G. 1996. Localization of grasp representations in humans by positron emission tomography. 2. Observation compared with imagination. Exp Brain Res 112:103-111.

Grezes, J., Costes, N., and Decety, J. 1999. The effects of learning and intention on the neural network involved in the perception of meaningless actions. Brain 122 ( Pt 10):1875-1887.

76

Grezes, J., Fonlupt, P., Bertenthal, B., Delon-Martin, C., Segebarth, C., and Decety, J. 2001. Does perception of biological motion rely on specific brain regions? Neuroimage 13:775-785.

Grossman, E., Donnelly, M., Price, R., Pickens, D., Morgan, V., Neighbor, G., and Blake, R. 2000. Brain areas involved in perception of biological motion. J Cogn Neurosci 12:711-720.

Guyton, A., and Hall, J. 1996. Textbook of Medical Physiology. WB Saunders Company.

Haight, J.R. 1972. The general organization of somatotopic projections to SII cerebral neocortex in the cat. Brain Res 44:483-502.

Halgren, E., Baudena, P., Heit, G., Clarke, J.M., Marinkovic, K., and Clarke, M. 1994. Spatio-temporal stages in face and word processing. I. Depth-recorded potentials in the human occipital, temporal and parietal lobes. J Physiol Paris 88:1-50.

Halgren, E., Raij, T., Marinkovic, K., Jousmäki, V., and Hari, R. 2000. Cognitive response profile of the human fusiform face area as determined by MEG. Cereb Cortex 10:69-81.

Hämäläinen, M., Hari, R., Ilmoniemi, R., Knuutila, J., and Lounasmaa, O.V. 1993. Magnetoencephalography – theory, instrumentation, and applications to noninvasive studies of the working human brain. Reviews of Modern Physics 65:413-497.

Hammes, J.G., and Langdell, T. 1981. Precursors of symbol formation and childhood autism. J Autism Dev Disord 11:331-346.

Happe, F.G. 1994a. An advanced test of theory of mind: understanding of story characters' thoughts and feelings by able autistic, mentally handicapped, and normal children and adults. J Autism Dev Disord 24: 129 -154.

Happe, F.G. 1994b. Wechsler IQ profile and theory of mind in autism: a research note. J Child Psychol  Psychiatry 35:1461-1471.

Happe, F.G. 1995. The role of age and verbal ability in the theory of mind task performance of subjects with autism. Child Dev 66:843-855.

Happe, F., and Frith, U. 1996. The neuropsychology of autism. Brain 119 ( Pt 4):1377-1400.

Happe, F., Ehlers, S., Fletcher, P., Frith, U., Johansson, M., Gillberg, C., Dolan, R., Frackowiak, R., and Frith, C. 1996. 'Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome. Neuroreport 8:197-201.

Hari, R. 1990. The neuromagnetic method in the study of the human auditory cortex. In Auditory Evoked Magnetic Fields and Electric Potentials (F. Grandori, M. Hoke, G.L. Romani, Eds.), pp. 222-282. Karger, Basel.

Hari, R. 1991. On brain's magnetic responses to sensory stimuli. J Clin Neurophysiol 8:157-169.

Hari, R., and Salmelin, R. 1997. Human cortical oscillations: a neuromagnetic view through the skull. Trends Neurosci 20:44-49.

Hari, R., Hämäläinen, M., Kaukoranta, E., Reinikainen, K., and Teszner, D. 1983. Neuromagnetic responses from the second somatosensory cortex in man. Acta Neurol Scand 68:207-212.

Hari, R., Reinikainen, K., Kaukoranta, E., Hämäläinen, M., Ilmoniemi, R., Penttinen, A., Salminen, J., and Teszner, D. 1984. Somatosensory evoked cerebral magnetic fields from SI and SII in man. Electroencephalogr Clin Neurophysiol 57:254-263.

Hari, R., Karhu, J., Hämäläinen, M., Knuutila, J., Salonen, O., Sams, M., and Vilkman, V. 1993. Functional organization of the human first and second somatosensory cortices: a neuromagnetic study. Eur J Neurosci 5:724-734.

77

Hari, R., Hänninen, R., Mäkinen, T., Jousmäki, V., Forss, N., Seppä, M., and Salonen, O. 1998. Three hands: fragmentation of bodily awareness. Neurosci Lett 240:131-134.

Hari, R., and Forss, N. 1999. Magnetoencephalography in the study of human somatosensory cortical processing. Philos Trans R Soc Lond B Biol Sci 354:1145-1154.

Hashimoto, T., Tayama, M., Murakawa, K., Yoshimoto, T., Miyazaki, M., Harada, M., and Kuroda, Y. 1995. Development of the brainstem and cerebellum in autistic patients. J Autism Dev Disord 25:1-18.

Hasselmo, M.E., Rolls, E.T., Baylis, G.C., and Nalwa, V. 1989. Object-centered encoding by face-selective neurons in the cortex in the superior temporal sulcus of the monkey. Exp Brain Res 75:417-429.

Haxby, J.V., Hoffman, E.A., and Gobbini, M.I. 2000. The distributed human neural system for face perception. Trends Cogn Sci 4:223-233.

Haznedar, M.M., Buchsbaum, M.S., Metzger, M., Solimando, A., Spiegel-Cohen, J., and Hollander, E. 1997. Anterior cingulate gyrus volume and glucose metabolism in autistic disorder. Am J Psychiatry 154:1047-1050.

Heimann, M., Ullstadius, E., Dahlgren, S.O., and Gillberg, C. 1992. Imitation in autism: A preliminary research note. Behav Neurol 5:219-227.

Hellgren, L., Gillberg, I.C., Bagenholm, A., and Gillberg, C. 1994. Children with deficits in attention, motor control and perception (DAMP) almost grown up: psychiatric and personality disorders at age 16years. J Child Psychol Psychiatry 35:1255-1271.

Hobson, R.P. 1986a. The autistic child's appraisal of expressions of emotion. J Child Psychol Psychiatry 27:321-342. Hobson, R.P. 1986b. The autistic child's appraisal of expressions of emotion: a further study. J Child Psychol Psychiatry 27:671-680.

Hobson, R.P., and Lee, A. 1999. Imitation and identification in autism. J Child Psychol Psychiatry 40: 649 - 659.

Hoffman, E.A., and Haxby, J.V. 2000. Distinct representations of eye gaze and identity in the distributed human neural system for face perception. Nat Neurosci 3:80-84.

Howlin, P., Wing, L., and Gould, J. 1995. The recognition of autism in children with Down syndrome-implications for intervention and some speculations about pathology. Dev Med Child Neurol 37:406-414.

Hsiao, S.S., O'Shaughnessy, D.M., and Johnson, K.O. 1993. Effects of selective attention on spatial form processing in monkey primary and secondary somatosensory cortex. J Neurophysiol 70:444-447.

Huttunen, J., and Homberg, V. 1991. Modification of cortical somatosensory evoked potentials during tactile exploration and simple active and passive movements. Electroencephalogr Clin Neurophysiol 81:216-223.

Huttunen, J., Wikström, H., Korvenoja, A., Seppäläinen, A.-M., Aronen, H., and Ilmoniemi, R. 1996. Significance of the second somatosensory cortex in sensorimotor integration: enhancement of sensory responses during finger movements. NeuroReport 7:1009-1012.

Iacoboni, M., Woods, R.P., Brass, M., Bekkering, H., Mazziotta, J.C., and Rizzolatti, G. 1999. Cortical mechanisms of human imitation. Science 286:2526-2528.

Iacoboni, M., Koski, L.M., Brass, M., Bekkering, H., Woods, R.P., Dubeau, M.C., Mazziotta, J.C., and Rizzolatti, G. 2001. Reafferent copies of imitated actions in the right superior temporal cortex. Proc Natl Acad Sci U S A 98:13995-13999.

78

Itakura, S. 1996. Manual action in infant chimpanzees: a preliminary study. Percept Mot Skills 83:611- 614.

Jamain, S., Quach, H., Betancur, C., Rastam, M., Colineaux, C., Gillberg, I.C., Soderstrom, H., Giros, B., Leboyer, M., Gillberg, C., and Bourgeron, T. 2003. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34:27-29.

Järvelainen, J., Schürmann, M., Avikainen, S., and Hari, R. 2001. Stronger reactivity of the human primary motor cortex during observation of live rather than video motor acts. Neuroreport 12:3493-3495.

Järveläinen, J., Schürmann, M., and Hari, R. 2003. Activation of the human primary motor cortex during observation of tool use. Neuroimage (under revision).

Jeannerod, M. 1994. The representing brain: neural correlates of motor intention and imagery. Behav Brain Sci 17:187-245.

Jeannerod, M., Arbib, M.A., Rizzolatti, G., and Sakata, H. 1995. Grasping objects: the cortical mechanisms of visuomotor transformation. Trends Neurosci 18:314-320.

Johansson, M., Wentz, E., Fernell, E., Stromland, K., Miller, M.T., and Gillberg, C. 2001. Autistic spectrum disorders in Mobius sequence: a comprehensive study of 25 individuals. Dev Med Child Neurol 43:338-345.

Jones, E.G., and Powell, T.P. 1969. Connexions of the somatic sensory cortex of the rhesus monkey. I. Ipsilateral cortical connexions. Brain 92:477-502.

Jure, R., Rapin, I., and Tuchman, R.F. 1991. Hearing-impaired autistic children. Dev Med Child Neurol 33:1062-1072.

Kadesjö, B., Gillberg, C., and Hagberg, B. 1999. Brief report: autism and Asperger syndrome in seven- year-old children: a total population study. J Autism Dev Disord 29:327-331.

Kakigi, R., and Jones, S.J. 1985. Effects on median nerve SEPs of tactile stimulation applied to adjacent and remote areas of the body surface. Electroencephalogr Clin Neurophysiol 62:252-265.

Kakigi, R., Koyama, S., Hoshiyama, M., Watanabe, S., Shimojo, M., and Kitamura, Y. 1995. Gating of somatosensory evoked responses during active finger movements magnetoencephalographic studies. J Neurol Sci 128:195-204.

Kandel, E., and Jessell, T.M. 1991. Touch. In Principles of Neural Science (E. Kandel, J.H. Schwartz, T.M. Jessell, Eds.), pp. 367-384. Prentice-Hall International Inc.

Kanner, L. 1943. Autistic disturbances of affective contact. Nervous Child 2:217-250.

Kaukoranta, E., Hari, R., Hämäläinen, M., and Huttunen, J. 1986. Cerebral magnetic fields evoked by peroneal nerve stimulation. Somatosens Res 3:309-321.

Kawashima, R., Sugiura, M., Kato, T., Nakamura, A., Hatano, K., Ito, K., Fukuda, H., Kojima, S., and Nakamura, K. 1999. The human amygdala plays an important role in gaze monitoring. A PET study. Brain 122 ( Pt 4):779-783.

Kemper, T.L., and Bauman, M. 1998. Neuropathology of infantile autism. J Neuropathol Exp Neurol 57: 645 -652.

Kiehl, K.A., Smith, A.M., Hare, R.D., Mendrek, A., Forster, B.B., Brink, J., and Liddle, P.F. 2001. Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging. Biol Psychiatry 50:677-684.

Klin, A., Sparrow, S.S., and Volkmar, F.R. 2000. Asperger Syndrome, Guilford, New York.

79

Klin, A., Volkmar, F.R., and Sparrow, S.S. 1992. Autistic social dysfunction: some limitations of the theory of mind hypothesis. J Child Psychol Psychiatry 33:861-876.

Klin, A., Volkmar, F.R., Sparrow, S.S., Cicchetti, D.V., and Rourke, B.P. 1995. Validity and neuropsychological characterization of Asperger syndrome: convergence with nonverbal learning disabilities syndrome. J Child Psychol Psychiatry 36:1127-1140.

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.

Kracke, I. 1994. Developmental prosopagnosia in Asperger syndrome: presentation and discussion of an individual case. Dev Med Child Neurol 36:873-886.

Kuhlman, W.N. 1978. Functional topography of the human mu rhythm. Electroencephalogr Clin Neurophysiol 44:83-93.

Kurata, K., and Tanji, J. 1986. Premotor cortex neurons in macaques: activity before distal and proximal forelimb movements. J Neurosci 6:403-411.

Lainhart, J.E., Piven, J., Wzorek, M., Landa, R., Santangelo, S.L., Coon, H., and Folstein, S.E. 1997. Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry 36:282-290.

Lam, K., Kakigi, R., Kaneoke, Y., Naka, D., Maeda, K., and Suzuki, H. 1999. Effects of visual and auditory stimulation on somatosensory evoked magnetic fields. Clin Neurophysiol 110:295-304.

Lamme, V.A., and Roelfsema, P.R. 2000. The distinct modes of vision offered by feedforward and recurrent processing. Trends Neurosci 23:571-579.

Langton, S.R., and Bruce, V. 2000. You must see the point: automatic processing of cues to the direction of social attention. J Exp Psychol Hum Percept Perform 26:747-757.

Langton, S.R., Watt, R.J., and Bruce, I.I. 2000. Do the eyes have it? Cues to the direction of social attention. Trends Cogn Sci 4:50-59.

Leslie, A.M., and Frith, U. 1987. Metarepresentation and autism: how not to lose one's marbles. Cognition 27:291-294.

Liberman, A.M., and Mattingly, I.G. 1985. The motor theory of speech perception revised. Cognition 21: 1 - 36.

Liberman, A.M., and Whalen, D.H. 2000. On the relation of speech to language. Trends in Cognitive Sciences 4:187-196.

Lin, Y.Y., Simoes, C., Forss, N., and Hari, R. 2000. Differential effects of muscle contraction from various body parts on neuromagnetic somatosensory responses. Neuroimage 11:334-40.

Liu, J., Harris, A., and Kanwisher, N. 2002. Stages of processing in face perception: an MEG study. Nat Neurosci 5:910-916.

Lopes da Silva, F.H. 1991. Neural mechanisms underlying brain waves:from neural membranes to networks. Electroencephalogr Clin Neurophysiol 79:81-93.

Lord, C., Cook, E.H., Leventhal, B.L., and Amaral, D.G. 2000. Autism spectrum disorders. Neuron 28:355-363.

Loveland, K.A., Tunali-Kotoski, B., Pearson, D.A., Brelsford, K.A., Ortegon, J., and Chen, R. 1994. Imitation and expression of facial affect in autism. Dev Psychopathol 6:433-444.

Lu, Z.-L., Wang, J.-Z., and Williamson, S.J. 1992. Neuronal sources of human parietooccipital alpha rhythm. In Biomagnetism:Clinical aspects,Excerpta Medica (M. Hoke, S. Erne ́, Y. Okada, G. Romani, Eds.), pp. 33-37. Elsevier Science Publishers B.V, Amsterdam.

80

Lütkenhoner, B., Lammertmann, C., Simoes, C., and Hari, R. 2002. Magnetoencephalographic correlates of audiotactile interaction. Neuroimage 15:509-522.

Martin, J.H. 1991. The Collective Electrical Behavior of Cortical Neurons: The Electroencephalogram and the Mechanisms of Epilepsy. In Principles of Neural Science (E. Kandel, J.H. Schwartz, T.M. Jessell, Eds.), pp. 777-791. Prentice-Hall International Inc.

Martin, J.H., and Jessell, T.M. 1991a. Anatomy of the somatic sensory system. In Principles of Neural Science (E. Kandel, J.H. Schwartz, T.M. Jessell, Eds.), pp. 353-366. Prentice-Hall International Inc.

Martin, J.H., and Jessell, T.M. 1991b. Modality coding in the somatic sensory system. In Principles of Neural Science (E. Kandel, J.H. Schwartz, T.M. Jessell, Eds.), pp. 341-352. Prentice-Hall International Inc.

Matelli, M., Luppino, G., and Rizzolatti, G. 1985. Patterns of cytochrome oxidase activity in the frontal agranular cortex of the macaque monkey. Behav Brain Res 18:125-136.

Matelli, M., Camarda, R., Glickstein, M., and Rizzolatti, G. 1986. Afferent and efferent projections of the inferior area 6 in the macaque monkey. J Comp Neurol 251:281-98.

McCarthy, G., Allison, T., and Spences, D. 1993. Localization of the face area of human sensorimotor cortex by intracranial rcording of somatosensory evoked potentials. J Neurosurg 79:874-884.

McGuire, P.K., Paulesu, E., Frackowiak, R.S., and Frith, C.D. 1996. Brain activity during stimulus independent thought. Neuroreport 7:2095-2099.

McKelvey, J.R., Lambert, R., Mottron, L., and Shevell, M.I. 1995. Right-hemisphere dysfunction in Asperger's syndrome. J Child Neurol 10:310-314.

Mehta, A.D., Ulbert, I., and Schroeder, C.E. 2000. Intermodal selective attention in monkeys. II: physiological mechanisms of modulation. Cereb Cortex 10:359-370.

Meltzoff, A.N., and Moore, M.K. 1977. Imitation of facial and manual gestures by human neonates. Science 198:74-78.

Meltzoff, A., and Gopnik, A. 1993. The role of imitation in understanding persons and developing a theory of mind. In Understanding other minds: perspectives from autism (S. Baron-Cohen, H. Tager-Flusberg, D. Cohen, Eds.), Oxford University Press, Oxford.

Mesulam, M.M. 1990. Large-scale neurocognitive networks and distributed processing for attention, language, and memory. Ann Neurol 28:597-613.

Mima, T., Nagamine, T., Nakamura, K., and Shibasaki, H. 1998. Attention modulates both primary and second somatosensory cortical activities in humans: a magnetoencephalographic study. J Neurophysiol 80:2215-2221.

Morgan, S.B., Cutrer, P.S., Coplin, J.W., and Rodrigue, J.R. 1989. Do autistic children differ from retarded and normal children in Piagetian sensorimotor functioning? J Child Psychol Psychiatry 30:857-864.

Morris, J.S., Frith, C.D., Perrett, D.I., Rowland, D., Young, A.W., Calder, A.J., and Dolan, R.J. 1996. A differential neural response in the human amygdala to fearful and happy facial expressions. Nature 383:812-815.

Murata, A., Fadiga, L., Fogassi, L., Gallese, V., Raos, V., and Rizzolatti, G. 1997. Object representation in the ventral premotor cortex (area F5) of the monkey. J Neurophysiol 78:2226-22230.

Murray, E.A., and Mishkin, M. 1984. Relative contributions of SII and area 5 to tactile discrimination in monkeys. Behav Brain Res 11:67-83.

81

Murray, G.M., Zhang, H.Q., Kaye, A.N., Sinnadurai, T., Campbell, D.H., and Rowe, M.J. 1992. Parallel processing in rabbit first (SI) and second (SII) somatosensory cortical areas: effects of reversible inactivation by cooling of SI on responses in SII. J Neurophysiol 68:703-710.

Niedermeyer, E., and Lopes da Silva, F. (Eds.), Electroencephalography. Basic Principles Clinical Applications and Related Fields (Williams & Williams Europe LTD, 1998).

Nieminen-von Wendt, T., Salonen, O., Vanhala, R., Kulomäki, T., von Wendt, L., and Autti, T. 2002. A quantitative controlled MRI study of the brain in 28 persons with Asperger syndrome. Int J Circumpolar Health 61 Suppl 2:22-35.

Nishitani, N., and Hari, R. 2000. Temporal dynamics of cortical representation for action. Proc Natl Acad Sci U S A 97:913-918.

Nishitani, N., and Hari, R. 2002. Viewing lip forms: cortical dynamics. Neuron 36:1211-1220.

Ohta, M. 1987. Cognitive disorders of infantile autism: a study employing the WISC, spatial relationship conceptualization, and gesture imitations. J Autism Dev Disord 17:45-62.

Olsson, I., Steffenburg, S., and Gillberg, C. 1988. Epilepsy in autism and autisticlike conditions. A population-based study. Arch Neurol 45:666-668.

Oram, M.W., and Perrett, D.I. 1996. Integration of form and motion in the anterior superior temporal polysensory area (STPa) of the macaque monkey. J Neurophysiol 76:109-129.

Oram, M.W., and Richmond, B.J. 1999. I see a face-a happy face. Nat Neurosci 2:856-858.

Ozonoff, S., Rogers, S.J., and Pennington, B.F. 1991. Asperger's syndrome: evidence of an empirical distinction from high-functioning autism. J Child Psychol Psychiatry 32:1107-1122.

Paradiso, S., Johnson, D.L., Andreasen, N.C., O'Leary, D.S., Watkins, G.L., Ponto, L.L., and Hichwa, R.D. 1999. Cerebral blood flow changes associated with attribution of emotional valence to pleasant, unpleasant, and neutral visual stimuli in a PET study of normal subjects. Am J Psychiatry 156:1618-1629.

Pelphrey, K.A., Sasson, N.J., Reznick, J.S., Paul, G., Goldman, B.D., and Piven, J. 2002. Visual scanning of faces in autism. J Autism Dev Disord 32:249-261.

Penfield, W., and Jasper, H., Epilepsy and the Functional Anatomy of the Human Brain (Little, Brown and Company, Boston, 1954).

Pennington, B.F., and Ozonoff, S. 1996. Executive functions and developmental psychopathology. J Child Psychol Psychiatry 37:51-87.

Perner, J. 1996. Simulation as explicitation of prediction-implicit knowledge about the mind: arguments for a simulation-theory mix. In Theories of Theories of Mind (P. Carruthers, P.K. Smith, Eds.), pp. 90-104. Cambridge University Press, Cambridge.

Perrett, D.I., Smith, P.A., Potter, D.D., Mistlin, A.J., Head, A.S., Milner, A.D., and Jeeves, M.A. 1985. Visual cells in the temporal cortex sensitive to face view and gaze direction. Proc R Soc Lond B Biol Sci 223:293-317.

Perrett, D.I., Harries, M.H., Bevan, R., Thomas, S., Benson, P.J., Mistlin, A.J., Chitty, A.J., Hietanen, J.K., and Ortega, J.E. 1989. Frameworks of analysis for the neural representation of animate objects and actions. J Exp Biol 146:87-113.

Perrett, D., Mistlin, A.J., Harries, M.H., and Chitty, A.J. 1990. Understanding the visual appearance and consequence of hand actions. In Vision and action:the control of grasping (M.A. Goodale, Eds.), pp. 163 - 342. NJ: Ablex, Norwood.

82

Perrett, D.I., Hietanen, J.K., Oram, M.W., and Benson, P.J. 1992. Organization and functions of cells responsive to faces in the temporal cortex. Philos Trans R Soc Lond B Biol Sci 335:23-30.

Pessoa, L., McKenna, M., Gutierrez, E., and Ungerleider, L.G. 2002. Neural processing of emotional faces requires attention. Proc Natl Acad Sci U S A 99:11458-11463.

Petitto, L.A., Holowka, S., Sergio, L.E., and Ostry, D. 2001. Language rhythms in baby hand movements. Nature 413:35-36.

Petrides, M., and Pandya, D.N. 1984. Projections to the frontal cortex from the posterior parietal region in the rhesus monkey. J Comp Neurol 228:105-116.

Petrides, M., and Pandya, D.N. 1999. Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns. Eur J Neurosci 11:1011-1036.

Pfurtscheller, G., and Aranibar, A. 1979. Evaluation of event-related desynchronization (ERD) preceding and following voluntary self-paced movement. Electroencephalogr Clin Neurophysiol 46:138-146.

Piven, J., Arndt, S., Bailey, J., Havercamp, S., Andreasen, N.C., and Palmer, P. 1995. An MRI study of brain size in autism. Am J Psychiatry 152:1145-1149.

Pons, T.P., Garraghty, P.E., Friedman, D.P., and Mishkin, M. 1987. Physiological evidence for serial processing in somatosensory cortex. Science 237:417-419.

Poranen, A., and Hyvärinen, J. 1982. Effects of attention on multiunit responses to vibration in the somatosensory regions of the monkey's brain. Electroencephalogr Clin Neurophysiol 53:525-537.

Posner, M.I. 1980. Orienting of attention. Q J Exp Psychol 32:3-25.

Preisler, G., Ahlstrom, M., and Tvingstedt, A.L. 1997. The development of communication and language in deaf preschool children with cochlear implants. Int J Pediatr Otorhinolaryngol 41:263-272.

Puce, A., and Perrett, D. 2003. Electrophysiology and brain imaging of biological motion. Philos Trans R Soc Lond B Biol Sci 358:435-445.

Puce, A., Allison, T., Bentin, S., Gore, J.C., and McCarthy, G. 1998. Temporal cortex activation in humans viewing eye and mouth movements. J Neurosci 18:2188-2199.

Puce, A., Allison, T., and McCarthy, G. 1999. Electrophysiological studies of human face perception. III: Effects of top-down processing on face-specific potentials. Cereb Cortex 9:445-458.

Ramachandran, V.S., and Rogers-Ramachandran, D. 1996. Denial of disabilities in anosognosia. Nature 382:501.

Randolph, M., and Semmes, J. 1974. Behavioral consequences of selective subtotal ablations in the postcentral gyrus of macaca mulatta. Brain Research 70:55–70.

Richer, F., Martinez, M., Robert, M., Bouvier, G., and Saint-Hilaire, J.M. 1993. Stimulation of human somatosensory cortex: tactile and body displacement perceptions in medial regions. Exp Brain Res 93:173-176.

Ritvo, E.R., Freeman, B.J., Scheibel, A.B., Duong, T., Robinson, H., Guthrie, D., and Ritvo, A. 1986. Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report. Am J Psychiatry 143:862-866.

Rizzolatti, G., and Arbib, M.A. 1998. Language within our grasp. Trends Neurosci 21:188-194.

Rizzolatti, G., and Luppino, G. 2001. The cortical motor system. Neuron 31:889-901.

83

Rizzolatti, G., Scandolara, C., Gentilucci, M., and Camarda, R. 1981. Response properties and behavioral modulation of "mouth" neurons of the postarcuate cortex (area 6) in macaque monkeys. Brain Res 225:421-424.


[HM: Rizzo puhuu "suupeilineuroneita" jo 1981, 15 vuotta ennen "yllättäviä peilineuronilöytöjä"...

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.

Rizzolatti, G., Fadiga, L., Gallese, V., and Fogassi, L. 1996a. Premotor cortex and the recognition of motor actions. Brain Res Cogn Brain Res 3:131-141.

Rizzolatti, G., Fadiga, L., Matelli, M., Bettinardi, V., Paulesu, E., Perani, D., and Fazio, F. 1996b. Localization of grasp representations in humans by PET: 1. Observation versus execution. Exp Brain Res 111:246-252.

Rizzolatti, G., Fadiga, L., Fogassi, L., and Gallese, V. 1999. Resonance behaviors and mirror neurons. Arch Ital Biol 137:85-100.

Rizzolatti, G., Fogassi, L., and Gallese, V. 2001. Neurophysiological mechanisms underlying the understanding and imitation of action. Nat Rev Neurosci 2:661-670.

Rodier, P.M., Ingram, J.L., Tisdale, B., Nelson, S., and Romano, J. 1996. Embryological origin for autism: developmental anomalies of the cranial nerve motor nuclei. J Comp Neurol 370:247-261.

Roelfsema, P.R., and Singer, W. 1998. Detecting connectedness. Cereb Cortex 8:385-396.

Rogers, S. 1999. An examination of the imitation deficit in autism. In Imitation in infancy (J. Nadel, G. Butterworth, Eds.), pp. 255-283. Cambridge University Press, Cambridge.

Rogers, S., and Pennington, B.F. 1991. A theoretical approach to the deficits in infantile autism. Dev Psychopathol 3:137-162.

Rogers, S.J., Bennetto, L., McEvoy, R., and Pennington, B.F. 1996. Imitation and pantomime in high- functioning adolescents with autism spectrum disorders. Child Dev 67:2060-2073.

Rolls, E.T. 2000. The orbitofrontal cortex and reward. Cereb Cortex 10:284-294.

Rosen, B.R., Buckner, R.L., and Dale, A.M. 1998. Event-related functional MRI: past, present, and future. Proc Natl Acad Sci U S A 95:773-780.

Ruby, P., and Decety, J. 2001. Effect of subjective perspective taking during simulation of action: a PET investigation of agency. Nat Neurosci 4:546-550.

Rutter, M., and Schopler, E. 1987. Autism and pervasive developmental disorders: concepts and diagnostic issues. J Autism Dev Disord 17:159-186.

Salenius, S., Kajola, M., Thompson, W.L., Kosslyn, S., and Hari, R. 1995. Reactivity of magnetic parieto-occipital alpha rhythm during visual imagery. Electroencephalogr Clin Neurophysiol 95:453-462.

Salenius, S., Salmelin, R., Neuper, C., Pfurtscheller, G., and Hari, R. 1996. Human cortical 40 Hz rhythm is closely related to EMG rhythmicity. Neurosci Lett 213:75-78.

Salenius, S., Schnitzler, A., Salmelin, R., Jousmäki, V., and Hari, R. 1997. Modulation of human cortical rolandic rhythms during natural sensorimotor tasks. Neuroimage 5:221-228.

Salmelin, R., and Hari, R. 1994. Spatiotemporal characteristics of sensorimotor neuromagnetic rhythms related to thumb movement. Neuroscience 60:537-550.

Salmelin, R., Hämäläinen, M., Kajola, M., and Hari, R. 1995. Functional segregation of movement- related rhythmic activity in the human brain. NeuroImage 2:237-243.

84

Sams, M., Hietanen, J.K., Hari, R., Ilmoniemi, R.J., and Lounasmaa, O.V. 1997. Face-specific responses from the human inferior occipito-temporal cortex. Neuroscience 77:49-55.

Scaife, M., and Bruner, J.S. 1975. The capacity for joint visual attention in the infant. Nature 253: 265 - 266.

Schnitzler, A., Salenius, S., Salmelin, R., Jousmäki, V., and Hari, R. 1995a. Involvement of primary somatomotor cortex in motor imagery: a neuromagnetic study. Society for Neuroscience Abstracts 21:518.

Schnitzler, A., Salenius, S., Salmelin, R., Jousmäki, V., and Hari, R. 1997. Involvement of primary motor cortex in motor imagery: a neuromagnetic study. Neuroimage 6:201-208.

Schnitzler, A., Salmelin, R., Salenius, S., Jousmäki, V., and Hari, R. 1995b. Tactile information from the human hand reaches the ipsilateral primary somatosensory cortex. Neuroscience Letters 200:25-28.

Schultz, R.T., Grelotti, D.J., Klin, A., Kleinman, J., Van der Gaag, C., Marois, R., and Skudlarski, P. 2003. The role of the fusiform face area in social cognition: implications for the pathobiology of autism. Philos Trans R Soc Lond B Biol Sci 358:415-427.

Semrud-Clikeman, M., and Hynd, G.W. 1990. Right hemispheric dysfunction in nonverbal learning disabilities: social, academic, and adaptive functioning in adults and children. Psychol Bull 107:196-209.

Shah, A., and Frith, U. 1983. An islet of ability in autistic children: a research note. J Child Psychol Psychiatry 24:613-620.

Siegal, M., Carrington, J., and Radel, M. 1996. Theory of mind and pragmatic understanding following right hemisphere damage. Brain Lang 53:40-50.

Sigman, M., and Ungerer, J.A. 1984. Attachment behaviors in autistic children. J Autism Dev Disord 14:231-244.

Sigman, M., and Mundy, P. 1989. Social attachments in autistic children. J Am Acad Child Adolesc Psychiatry 28:74-81.

Simoes, C., and Hari, R. 1999. Relationship between contra- and ipsilateral stimulation in the human second somatosensory cortex SII. Neuroimage 10:408-416.

Simoes, C., Mertens, M., Forss, N., Jousmäki, V., Lütkenhoner, B., and Hari, R. 2001. Functional overlap of finger representations in human SI and SII cortices. J Neurophysiol 86:1661-1665.

Smalley, S.L., and Asarnow, R.F. 1990. Cognitive subclinical markers in autism. J Autism Dev Disord 20:271-278.

Smith, I.M., and Bryson, S.E. 1994. Imitation and action in autism: a critical review. Psychol Bull 116:259-273.

Starr, A., and Cohen, L.G. 1985. 'Gating' of somatosensory evoked potentials begins before the onset of voluntary movement in man. Brain Res 348:183-186.

Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I.C., Jakobsson, G., and Bohman, M. 1989. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 30:405-416.

Steinmetz, P.N., Roy, A., Fitzgerald, P.J., Hsiao, S.S., Johnson, K.O., and Niebur, E. 2000. Attention modulates synchronized neuronal firing in primate somatosensory cortex. Nature 404:187-190.

Stenbacka, L., Vanni, S., Uutela, K., and Hari, R. 2002. Comparison of minimum current estimate and dipole modeling in the analysis of simulated activity in the human visual cortices. Neuroimage 16: 936 - 943.

84

Sams, M., Hietanen, J.K., Hari, R., Ilmoniemi, R.J., and Lounasmaa, O.V. 1997. Face-specific responses from the human inferior occipito-temporal cortex. Neuroscience 77:49-55.

Scaife, M., and Bruner, J.S. 1975. The capacity for joint visual attention in the infant. Nature 253:265- 266.

Schnitzler, A., Salenius, S., Salmelin, R., Jousmäki, V., and Hari, R. 1995a. Involvement of primary somatomotor cortex in motor imagery: a neuromagnetic study. Society for Neuroscience Abstracts 21:518.

Schnitzler, A., Salenius, S., Salmelin, R., Jousmäki, V., and Hari, R. 1997. Involvement of primary motor cortex in motor imagery: a neuromagnetic study. Neuroimage 6:201-208.

Schnitzler, A., Salmelin, R., Salenius, S., Jousmäki, V., and Hari, R. 1995b. Tactile information from the human hand reaches the ipsilateral primary somatosensory cortex. Neuroscience Letters 200:25-28.

Schultz, R.T., Grelotti, D.J., Klin, A., Kleinman, J., Van der Gaag, C., Marois, R., and Skudlarski, P. 2003. The role of the fusiform face area in social cognition: implications for the pathobiology of autism. Philos Trans R Soc Lond B Biol Sci 358:415-427.

Semrud-Clikeman, M., and Hynd, G.W. 1990. Right hemispheric dysfunction in nonverbal learning disabilities: social, academic, and adaptive functioning in adults and children. Psychol Bull 107:196-209.

Shah, A., and Frith, U. 1983. An islet of ability in autistic children: a research note. J Child Psychol Psychiatry 24:613-620.

Siegal, M., Carrington, J., and Radel, M. 1996. Theory of mind and pragmatic understanding following right hemisphere damage. Brain Lang 53:40-50.

Sigman, M., and Ungerer, J.A. 1984. Attachment behaviors in autistic children. J Autism Dev Disord 14:231-244.

Sigman, M., and Mundy, P. 1989. Social attachments in autistic children. J Am Acad Child Adolesc Psychiatry 28:74-81.

Simoes, C., and Hari, R. 1999. Relationship between contra- and ipsilateral stimulation in the human second somatosensory cortex SII. Neuroimage 10:408-416.

Simoes, C., Mertens, M., Forss, N., Jousmäki, V., Lütkenhoner, B., and Hari, R. 2001. Functional overlap of finger representations in human SI and SII cortices. J Neurophysiol 86:1661-1665.

Smalley, S.L., and Asarnow, R.F. 1990. Cognitive subclinical markers in autism. J Autism Dev Disord 20:271-278.

Smith, I.M., and Bryson, S.E. 1994. Imitation and action in autism: a critical review. Psychol Bull 116:259-273.

Starr, A., and Cohen, L.G. 1985. 'Gating' of somatosensory evoked potentials begins before the onset of voluntary movement in man. Brain Res 348:183-186.

Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I.C., Jakobsson, G., and Bohman, M. 1989. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 30:405-416.

Steinmetz, P.N., Roy, A., Fitzgerald, P.J., Hsiao, S.S., Johnson, K.O., and Niebur, E. 2000. Attention modulates synchronized neuronal firing in primate somatosensory cortex. Nature 404:187-190.

Stenbacka, L., Vanni, S., Uutela, K., and Hari, R. 2002. Comparison of minimum current estimate and dipole modeling in the analysis of simulated activity in the human visual cortices. Neuroimage 16:936- 943.

86

Vallbo, A.B., and Wessberg, J. 1993. Organization of motor output in slow finger movements in man. J Physiol 469:673-691.

Vogeley, K., Bussfeld, P., Newen, A., Herrmann, S., Happe, F., Falkai, P., Maier, W., Shah, N.J., Fink, G.R., and Zilles, K. 2001. Mind reading: neural mechanisms of theory of mind and self-perspective. Neuroimage 14:170-181.

Wapner, S., and Cirillo, L. 1968. Imitation of a model's hand movements: age changes in transposition of left-right relations. Child Dev 39:887-894.

Whalen, P.J., Rauch, S.L., Etcoff, N.L., McInerney, S.C., Lee, M.B., and Jenike, M.A. 1998. Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge. J Neurosci 18:411-418.

Whiten, A., and Brown, J. 1999. Imitation and the reading of other minds: perspectives from the study of autism, normal children and non-human primates. In Intersubjective communication and emotion in ontogeny: A sourcebook (S. Braten, Eds.), pp. 260-280. Cambridge University Press, Cambridge.

Wicker, B., Michel, F., Henaff, M.A., and Decety, J. 1998. Brain regions involved in the perception of gaze: a PET study. Neuroimage 8:221-227.

 

Williams, J.H., Whiten, A., Suddendorf, T., and Perrett, D.I. 2001. Imitation, mirror neurons and autism.

Neurosci Biobehav Rev 25:287-295.

Williamson, S.J., and Kaufman, L. 1989. Advances in neuromagnetic instrumentation and studies of spontaneous brain activity. Brain Topogr 2:129-139.

Wimmer, H., and Perner, J. 1983. Beliefs about beliefs: representation and constraining function of wrong beliefs in young children's understanding of deception. Cognition 13:103-128.

Wing, L. 1981a. Asperger's syndrome: a clinical account. Psychol Med 11:115-129.

Wing, L. 1981b. Sex ratios in early childhood autism and related conditions. Psychiatry Res 5:129-37.

Wing, L. 1993. The definition and prevalence of autism: a review. Eur Child Adolesc Psychiatry 2:61-74.

Winner, E., Brownell, H., Happe, F., Blum, A., and Pincus, D. 1998. Distinguishing lies from jokes: theory of mind deficits and discourse interpretation in right hemisphere brain-damaged patients. Brain Lang 62:89-106.

Winston, J.S., Strange, B.A., O'Doherty, J., and Dolan, R.J. 2002. Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nat Neurosci 5:277-283.

Wohlschläger, A., and Bekkering, H. 2002. Is human imitation based on a mirror-neurone system? Some behavioural evidence. Exp Brain Res Imitation, mirror neurons and autism.143:335-341.

Wolff, S., and McGuire, R.J. 1995. Schizoid personality in girls: a follow-up study--what are the links with Asperger's syndrome? J Child Psychol Psychiatry 36:793-817.

Wood, C.C., Cohen, D., Cuffin, B.N., Yarita, M., and Allison, T. 1985. Electrical sources in human somatosensory cortex: identification by combined magnetic and potential recordings. Science 227:1051- 1053.

Wood, C.C., Spencer, D.D., Allison, T., McCarthy, G., Williamson, P.D., and Goff, W.R. 1988. Localization of human sensorimotor cortex during surgery by cortical surface recording of somatosensory evoked potentials. J Neurosurg 68:99-111.

Yang, T.T., Menon, V., Eliez, S., Blasey, C., White, C.D., Reid, A.J., Gotlib, I.H., and Reiss, A.L. 2002. Amygdalar activation associated with positive and negative facial expressions. Neuroreport 13:1737- 1741.

87

Yeargin-Allsopp, M., Rice, C., Karapurkar, T., Doernberg, N., Boyle, C., and Murphy, C. 2003. Prevalence of autism in a US metropolitan area. JAMA 289:49-55.

 

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https://www.cell.com/trends/cognitive-sciences/abstract/S1364-6613(04)00024-5

FOXP2 and the mirror system

DOI:https://doi.org/10.1016/j.tics.2004.01.007
 

Abstract

An inherited deficit in spoken language has been associated with a mutation in the forkhead box P2 ( FOXP2) gene on chromosome 7. A recent functional magnetic resonance imaging study has linked the deficit to underactivity in Broca's area during word generation, which in turn suggests a possible link between FOXP2 and the mirror-neuron system observed in the primate homologue of Broca's area. This link might have implications for the evolution of Broca's area and its role in speech.
 

References

  • Marcus, G.F.
  • Fisher, S.E.
FOXP2 in focus: what can genes tell us about speech and language?.
Trends Cogn. Sci. 2003; 7: 257-762
View in Article
  • Hurst, J.A.
  • et al.
An extended family with a dominantly inherited speech disorder.
Dev. Med. Child Neurol. 1990; 32: 352-355
View in Article
  • Lai, C.S.L.
  • et al.
A novel forkhead-domain gene is mutated in a severe speech and language disorder.
Nature. 2001; 413: 519-523
View in Article
  • Enard, W.
  • et al.
Molecular evolution of FOXP2, a gene involved in speech and language.
Nature. 2002; 418: 869-872
View in Article
  • Liégeois, F.
  • et al.
Language fMRI abnormalities associated with FOXP2 gene mutation.
Nat. Neurosci. 2003; 6: 1230-1237
View in Article
  • Gopnik, M.
Feature-blind grammar and dysphasia.
Nature. 1990; 344: 715
View in Article
  • Pinker, S.
The Language Instinct. Allen Lane, London, UK; 1994
View in Article
  • Vargha-Khadem, F.
  • et al.
Praxic and nonverbal deficits in a large family with a genetically transmitted speech and language disorder.
Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 930-933
View in Article
  • Watkins, K.E.
  • et al.
Behavioural analysis of an inherited speech and language disorder: comparison with acquired aphasia.
Brain. 2002; 125: 452-464
View in Article
  • Watkins, K.E.
  • et al.
MRI analysis of an inherited speech and language disorder: structural brain abnormalities.
Brain. 2002; 125: 465-478
View in Article
  • Crow, T.J.
Why cerebral asymmetry is the key to the origin of Homo sapiens: how to find the gene or eliminate the theory.
Curr. Psychol. Cognit. 1998; 17: 1237-1277
View in Article
  • Annett, M.
Handedness and Brain Asymmetry: The Right Shift Theory. Psychology Press, ; 2002
View in Article
  • McManus, I.C.
Handedness, language dominance and aphasia: a genetic model.
Psychol. Med. 1985; : 1-40
View in Article
  • Rizzolatti, G.
  • et al.
Premotor cortex and the recognition of motor actions.
Brain Res. Cognit. Brain Res. 1996; 3: 131-141
View in Article
  • Rizzolatti, G.
  • et al.
Neurophysiological mechanisms underlying action understanding and imitation.
Nat. Rev. Neurosci. 2001; 2: 661-670
View in Article
  • Rizzolatti, G.
  • Arbib, M.A.
Language within our grasp.
Trends Neurosci. 1998; 21: 188-194
View in Article
  • Corballis, M.C.
From Hand to Mouth: The Origins of Language. Princeton University Press, NJ, USA; 2002
View in Article
  • Pinker, S.
Language as an adaptation to the cognitive niche.
in: M.H. Christiansen, S. Kirby (Eds.) Language Evolution. Oxford University Press, ; 2002: 17-37
View in Article
  • Ploog, D.
Is the neural basis of vocalization different in non-human primates and Homo sapiens?.
in: T.J. Crow (Ed.) The Speciation of Modern Homo Sapiens. Oxford University Press, ; 2002: 121-135
View in Article
  • Gardner, R.A.
  • Gardner, B.T.
Teaching sign language to a chimpanzee.
Science. 1969; 165: 664-672
View in Article
  • Savage-Rumbaugh, S.
  • et al.
Apes, Language, and the Human Mind. Oxford University Press, ; 1998
View in Article
  • Shu, W.
  • et al.
Characteristics of a new subfamily of winged-helix/forkhead (Fox) genes that are expressed in the heart and act as transcriptional repressors.
J. Biol. Chem. 2001; 276: 27488-27497
View in Article
  • MacLarnon, A.
  • Hewitt, G.
The evolution of human speech: the role of enhanced breathing control.
Am. J. Phys. Anthropol. 1999; 109: 341-363
View in Article

Corballis, M.C. The origins of modernity: Was autonomous speech the critical factor? Psychol. Rev. (in press).

View in Article

Article Info

IDENTIFICATION

DOI: 10.1016/j.tics.2004.01.007

Copyright

© 2004 Elsevier Science Ltd. Published by Elsevier Inc. All rights reserved.

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"In the last decade or so, we've come to realize that the mouse is really similar to humans," said Wolfgang Enard of the Max-Planck Institute for Evolutionary Anthropology. "The genes are essentially the same and they also work similarly." Because of that, scientists have learned a tremendous amount about the biology of human diseases by studying mice.

"With this study, we get the first glimpse that mice can be used to study not only disease, but also our own history."

Enard said his team is generally interested in the genomic differences that set humans apart from their primate relatives. One important difference between humans and chimpanzees they have studied are two amino acid substitutions in FOXP2. Those changes became fixed after the human lineage split from chimpanzees and earlier studies have yielded evidence that the gene underwent positive selection. That evolutionary change is thought to reflect selection for some important aspects of speech and language.


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https://reader.elsevier.com/reader/sd/7DE13466AC245BB500CFA9E5BF4B0D7CA9B77A5497E0CAB7195C2E30C95A4DF34AA279646AED38680CED4D2443079BED

 

Article

No Evidence for Recent Selection at FOXP2 among Diverse Human Populations Graphical

Sohini Ramachandran et. al.
 

No support for positive selection at FOXP2 in large genomic datasets.

Sample composition and genomic scale significantly affect

An intronic ROI within FOXP2 is expressed in human brain cells and cortical tissue

This ROI contains a large amount of constrained, human-specific polymorphisms