PERSPECTIVES

OPINION

Active perception: sensorimotor circuits as a cortical basis for language

Friedemann Pulvermller and Luciano Fadiga

Abstract | Action and perception are functionally linked in the brain, but a hotly debated question is whether perception and comprehension of stimuli depend on motor circuits. Brain language mechanisms are ideal for addressing this question. Neuroimaging investigations have found specific motor activations when subjects understand speech sounds, word meanings and sentence structures. Moreover, studies involving transcranial magnetic stimulation and patients with lesions affecting inferior frontal regions of the brain have shown contributions of motor circuits to the comprehension of phonemes, semantic categories and grammar. These data show that language comprehension benefits from frontocentral action systems, indicating that action and perception circuits are interdependent.
The brain collects information about the environment through sensory systems and computes motor responses. How sensory and motor systems interact and how higher cognitive processes contribute to these computations is not fully understood. An influential theory views input systems as separate from motor systems: input systems filter sensory input in a feedforward manner 1, resulting in perceptual processes which, after possible interaction with attention, emotion and memory modules, influence motor systems controlling actions2,3. According to this separation view, the posterior part of the cortex of higher mammals is mainly concerned with sensory information, whereas the frontal motor cortex (which includes premotor and primary motor areas) serves a slave role under the dictate of perceptual and cognitive systems. Recent years have seen major challenges to this hypothesis through the discovery of sensorimotor neurons that are active during both action execution and corresponding perceptions (see Supplementary information S1 (box)). The monkey premotor area F5 contains such mirror neurons, which show striking specificity: they fire during the execution of actions of a specific type (for example, peanut breaking) and
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comprehension. Recent research into the brain basis of language has shed light on the neural circuits underlying different facets of the perception and comprehension of signs, their meaning and syntactic structure. This information is essential for assessing the relevance of motor mechanisms in perception and comprehension. Here, we first highlight anatomical and neurocomputational data on the general properties of language circuits and then analytically review neurofunctional studies of phonological, semantic and syntactic processes in the healthy and functionally impaired human brain. This evidence leads us to conclude that language mechanisms involve functionally interdependent brain systems for action and perception.
Functional neuroanatomy of language Comparative neuroanatomical and neurophysiological studies have suggested that a sector of mirror neuron area F5 in macaques is cytoarchitectonically comparable to Brodmann area 44 (BA 44) in the human inferior frontal cortex, which is part of Brocas area13. Studies have shown this area to be active in human action observation, action imagery and language understanding 1416. This suggests a possible evolutionary relationship between monkey mirror neurons and the emergence of human language through a sensorimotor matching mechanism in the human motor brain that might be important for cognitive processes9. In macaques, extensive neuroanatomical links exist between premotor areas and parietal areas involved in somatosensory and visual processing and, consistent with these structural connections, all of these areas contain mirror neurons10,17. Despite anatomical and physiological evidence supporting a possible link between mirror neurons and human language, there is a fundamental quantitative difference between human language and the communication systems of apes and monkeys. Humans easily master vocabularies comprising tens of thousands of words and symbols, whereas our closest relatives use up to only 40 signs, including their species-specific calls18. In addition, only humans have wellknown syntactic abilities, which apply to all
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equally during the observation of another individual (monkey or human) performing the same action4. They may even respond to the sound of that action5. The multimodal action specificity of mirror neurons suggests actionperception integration at the neuronal level, possibly in the form of neuronal circuits distributed over sensory and motor areas6,7. According to this integration view, perception, cognition and motor control share neuronal mechanisms to which sensorimotor neurons are of key importance6,811. Actionperception circuits as a basis of higher cognition offer an alternative to the view that action and perception mechanisms are segregated. In the separation view, perception-related mirror activity in motor systems could be interpreted as sensory-tomotor overspill that does not contribute to perception. Motor system activation during perception would accordingly emerge owing to input from perceptual areas, but the opposite link from motor to perception circuits would either be absent or have no basic function in perception. The importance of sensory input for action control is widely accepted12, and an evaluation of and eventually a decision between the two theories depends on the relevance of activity in motor systems for perception and

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action domains (see the section on grammar, below). At the neuroanatomical level, the two principal regions for language the superior temporal areas adjacent to the auditory cortex and the inferior frontal areas anterior to the articulatory motor cortex are connected by several white-matter tracts: the extreme capsule, the uncinate fascicle and the arcuate fascicle. The arcuate fascicle is well developed in the left, language-dominant hemisphere of the human brain but weakly developed in apes and monkeys (FIG. 1). Thus, the substantial differences in vocabulary size and syntactic complexity have an anatomical correlate in frontotemporal actionperception connections, suggesting that these connections could be the basis of the differences. Humans are born with remarkable perceptual sensitivities that allow them to detect basic properties of speech that are common to all languages. However, during the first year of life, these sensitivities undergo modification, reflecting an exquisite tuning to phonological properties of the native language19,20. Interestingly, during this babbling phase (months 612), the sounds that babies articulate become increasingly similar to the types of speech sounds, or phonemes, that they hear frequently; such acousticphonological tuning to language-specific sounds is also manifest in neurophysiology 21,22, suggesting sensorimotor interactions. Rich links between articulatory and auditory neurons are required to learn the precise mapping between acoustic patterns and the motor programmes necessary for successful word repetition, which emerges after the babbling phase23. The articulation of a word (and the early babbling of syllables) is controlled by neuronal activity in the inferior frontal motor cortex, which is in turn controlled by inferior frontal premotor and prefrontal circuits (BOX 1). At the same time, speech sounds and spoken words elicit activity in the auditory system, mainly in superior temporal primary auditory, auditory belt and parabelt areas. Importantly, connections between these sites enable the cortex to strengthen these links and thereby store correlations between inferior frontal neurons that contribute to articulatory actions and superior temporal neurons that are involved in auditory perception. As neurons that frequently fire together also strengthen their mutual connections, early articulations and word production lead to the emergence of actionperception circuits for phonemes and words7,24. In addition, synaptic strengthening due to co-activation also suggests that somatosensory neurons might be involved in these actionperception circuits. Actionperception learning of speech sounds and spoken words requires strong, reciprocal superior temporalinferior frontal connections. As mentioned above, these connections are strong only in humans and are weak in non-human primates. This might therefore explain why language has not emerged in non-human primates. In addition, the brain laterality of language could be explained by the structural asymmetry of the arcuate fascicle, which is more pronounced in the left hemisphere in humans25, giving the left perisylvian cortex a privileged status in building actionperception circuits for speech7. This hypothesis does not rule out the possibility of the opposite causal link stronger fibres developing as a consequence of laterality but offers an explanation of language laterality based on anatomical and physiological observations. We acknowledge that, apart from action perception learning, the human brain also supports the purely perceptual learning of small vocabularies of word forms in the absence of articulation26, but note that
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a
Human PrCS CS IPS 46 45 47 9 44 6 STS 40 22 21 37 39

b
Syllable repetition PMd F3op

IFS

10

T1p

Chimpanzee CS IFS 46 8 PrCS 45 44 6 47 STS F3tri Macaque AS 6 STS F3orb T2a CS T2p IPS 40 22 37 39 Sentence comprehension FOP T 1a

IPS 7a 7b 22

45 44

FUS

Figure 1 | Cortical anatomy underlying language processing: from monkeys to humans. Nature Reviews | Neuroscience a | Frontotemporal connections in the left hemisphere of the brain in humans, chimpanzees and macaques. These frontotemporal connections are present in monkeys128 but became richer during evolution, especially the dorsal connection by way of the arcuate fascicle129. In humans, the frontotemporal link through the arcuate fascicle is stronger in the left hemisphere than in the right hemisphere25. The numbers indicate Brodmann areas. b | Frontotemporal connections in the human brain between areas that are active during syllable repetition and during sentence comprehension through the arcuate fascicle (upper arc in the top diagram) and the extreme capsule (lower arc in both diagrams). We propose that rich frontotemporal connections are necessary for binding auditory and articulatory information in actionperception circuits (BOX 1). AS, anterior sulcus; CS, central sulcus; FOP, frontal operculum; F3op, pars opercularis (also known as Brodmann area 44); F3orb, orbital part of the inferior frontal gyrus; F3tri, triangular part of the inferior frontal gyrus; FUS, fusiform gyrus; IFS, inferior frontal sulcus; IPS, intraparietal sulcus; PMd, dorsal premotor cortex; PrCS, precentral sulcus; STS, superior temporal sulcus; T1a, anterior part of the superior temporal gyrus; T2a, anterior part of the middle temporal gyrus; T1p, posterior part of the superior temporal gyrus; T2p, posterior part of the middle temporal gyrus. Part a is modified, with permission, from Nature Neuroscience REF. 129 (2008) Macmillan Publishers Ltd. All rights reserved. Part b is reproduced, with permission, from REF. 130 (2008) National Academy of Sciences.
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monkeys also exhibit this type of perceptual learning 27. Notably, children with severe neurological motor deficits that affected articulation had reduced auditory vocabularies that is, they understood fewer words than children with similar deficits that did not affect articulation28 a finding consistent with the importance of motor links for vocabulary learning. Neurocomputational studies of early stages of language acquisition and adult language processing further confirm the importance of actionperception links in building neuronal correlates of phonemes and words2931. Neuronal-network studies incorporating synaptic learning rules and neuroanatomical connectivity between simulated areas support the view that, in the healthy, non-deprived brain, correlated activation of connected articulatory and acoustic cortical systems leads to the emergence of distributed action perception circuits during language learning (BOX 1). The role of these circuits in sound and word processing is discussed below.
The motor side of speech perception When we articulate a syllable, a word or a sentence, our self-produced sounds stimulate the auditory system in the superior temporal cortex. However, activation of the superior temporal cortex, including the temporal plane, was also seen in subjects when the sounds created by their whispered articulations were masked by noise, and this activation increased with speech rate32, suggesting motor-to-auditory activation flow in the cortex during speech production. Conversely, listening to speech sounds that require strong articulatory activity especially the rolling r activates the motor system, as revealed by measuring muscle excitation following magnetic stimulation of the motor cortex 15,33. Neurometabolic studies confirm that the inferior frontal premotor cortex and the prefrontal cortex are active during the identification and discrimination of speech sounds and also during passive speech perception3437. Speech sounds elicit stronger activity than similar, non-speech stimuli in the anterior and lateral superior temporal cortex 38,39, and recent studies reported that this region also exhibits fine-grained activation differences depending on the phoneme type37,40,41. In speech production, phonetic-distinctive features for example, tongue tip-produced alveolar phonemes (such as t) versus lip-produced bilabial phonemes (such as p) show somatotopy in the way they are mapped onto the motor system (precentral gyrus). Interestingly, the lateral part of the
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Box 1 | Functional anatomy of language: from brain areas to neuronal circuits a b

M1 PF PM A1AB PB M1 PF PB AB A1

PM

Lesion in M1 PM PF PB AB A1

Speech production OK 5 3 7 12 51 100 Delay 0 23 14 12 34 0 Error 0 7 73 71 15 0 Fail 95 67 6 5 0 0

Speech perception OK 100 49 1 0 0 0 Delay 0 29 23 3 10 12 Error 0 22 70 9 3 5 Fail 0 0 6 88 87 83

Computational models that replicate cortical structure and function have provided evidence for the Nature Reviews | Neuroscience existence of actionperception circuits distributed over inferior frontal and superior temporal areas of the human cortex. Six main areas of the left-perisylvian language cortex are shown by different colours in part a of the figure. Part b shows the corresponding areas that were used in a model network architecture mimicking the language cortex30: primary auditory (A1), auditory belt (AB), auditory parabelt (PB) in the superior temporal region (Brodmann area 41 (BA 41), BA 42 and BA 22), prefrontal (PF; BA 45), premotor (PM; includes both BA 44 and BA 6) and primary motor (M1; BA 4) cortex in the inferior frontal cortex. Connections between the modelled areas incorporated links that have been shown in neuroanatomical studies (FIG. 1). The production of speech sounds and whole words was modelled by simultaneous activation of neurons in motor (M1) and auditory (A1) areas, leading to a spread of activation throughout the six areas of the model. As realistic Hebbian learning was used to modify the weights of connections, neurons that activated together became more strongly connected. This process yielded specific but partly overlapping distributed neuronal circuits for individual speech sounds and words. After learning, any stimulation of a words auditory neurons in A1 led to full activation of the entire circuit, even spreading towards its motor neurons in M1 (REFS 30,118). This observation shows that the word-specific neuronal assemblies developed by the model link together action and perception circuits. These and related studies29,119 show that human neuroanatomy and general neurophysiological principles produce actionperception circuits for language as a consequence of learning. The networks can be used to predict linguistic brain activation30. The actionperception model of word processing explains important features of language deficits caused by disease of the brain. Most of these deficits affect speech production as well as speech perception and comprehension. However, there can be a predominance of deficits in either the action or the perception domain. Inferior frontal lesions tend to cause pronounced deficits in speech production, whereas superior temporal lesions have the greatest effect on perception. The model explains these features as follows: multimodal deficits arise because lesions to the centre of the actionperception circuit (areas PM, PF, PB and AB) compromise circuit function in general. The double dissociation between motor (Brocas) aphasia and sensory (Wernickes) aphasia caused by inferior frontal (PF and PM) and superior temporal (AB and PB) lesions, respectively, arises because focal lesions of key loci within a distributed circuit have different effects on general network function: a lesion in a circuit towards its motor end reduces activity propagation to the motor output; a lesion close to its auditory end reduces the effect of incoming activity, in addition to the lesion effect on general circuit function. The closer a lesion is to the input or output fibres of the circuit, the greater the imbalance between deficits in action and perception. In the extreme, after a lesion in one of the peripheral areas of the network (M1 or A1), circuits are cut off from their output or input but circuit function is not substantially impaired; this results in isolated motor or auditory deficits. These conclusions were confirmed in a neurocomputational lesion study, in which 75% of the artificial neurons in each simulated area of the model of the language cortex were selectively damaged31. The table (see the figure, part c) lists the percentage of network responses that are correct and impaired after lesions in particular areas in simulations of word production and recognition. As distributed circuits explain the double dissociation between action and perception deficits, they provide an alternative to modular models according to which action and perception are supported by separate processing components (see also REF.3). Figures are reproduced, with permission, from REF. 30 (2008) Wiley-Blackwell.

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precentral cortex that is active in p sound production is also activated during listening to p sounds, and the inferior precentral area involved in producing a t sound is activated when hearing the sound37. Somatotopic activation in the motor system therefore not only reflects phonetic distinctions between speech sounds, but also indicates phonetic linguistic correspondence between articulated and heard phonemes and even includes specific information about how speech sounds are produced (FIG. 2). Whether other phonetic features (such as voicing and nasality) are also reflected in somatotopic motor system activation should be addressed in future studies. The motor somatotopy associated with hearing speech, as revealed in transcranial magnetic stimulation (TMS) and functional MRI studies15,37, shows that the motor system extracts fine-grained phonological information and suggests that this information is relevant in the speech perception process.
a Articulator movement
Silent articulation

Indeed, a group of theories has postulated that action mechanisms are important in speech perception24,4244. However, the functional-separation view of motor and sensory brain mechanisms questions such general relevance, an opinion that was also put forward in recent publications39,45 with the suggestion that motor processes that are involved in speech production do not directly contribute to speech perception and comprehension39. We now address this controversy by briefly reviewing the relevant data from neuropsychology. The separation of sensory and motor processes for language can be traced back to the comments of nineteenth-century neurologists on language deficits caused by brain lesions. Sensorial aphasia following posterior brain lesion was characterized as loss of understanding of spoken and written language but preservation of [the] faculty of volitional speech46, whereas motor aphasia following inferior frontal
Listening to syllables

Lip M1 % Response time

130 120 110 100 90 80

Labial Dental

Tongue M1

Tongue M1

Lip M1

Figure 2 | Speech sounds in motor systems. Neuroscience research has revealed the brain correlates Nature Reviews | Neuroscience of speech sounds and their phonetic features. These were found in the superior temporal cortex and also in the cortical motor system. a | Brain activation revealed by functional MRI during articulator movements (left panel; tongue movement shown in green and lip movement shown in red), silent articulation of syllables including t or p (middle panel; t articulation shown in green and p articulation shown in red) and listening to syllables including p and t sounds (right panel).The similarity between these activation patterns shows that, in the motor system, hearing speech sounds that are produced with the tongue and lips activates brain areas that are involved in the production of those tongue- and lip-related sounds and in simple repetitive tongue and lip movements14,37. b | Stimulation points in a transcranial magnetic stimulation study (left panel) and the resulting change in response times in a speech perception task (right panel). Consistent with the actionperception model (BOX 1), weak magnetic stimulation of the lip and tongue areas in the left, dominant hemisphere biases the perceptual system to hear the concordant speech sound (p in case of lip motor area stimulation) and to incorrectly perceive incongruent phonemes55. Part a is reproduced, with permission, from REF. 37 (2006) National Academy of Sciences. Part b is reproduced, with permission, from REF. 55 (2009) Cell Press.

lesions was characterized as loss of volitional speech with spared understanding of spoken words47. Clearly, such binary descriptions in terms of spared and impaired functions are inappropriate for describing the usually gradual (not all-or-nothing) effect of brain lesions, and it was Wernicke who highlighted specific problems in voluntary speech in cases of sensorial aphasia48. However, speech and language problems were not observed in patients with motor aphasia resulting from inferior frontal lesions4648. However, the deficit in speech comprehension in all types of aphasia including motor (also known as Brocas) aphasia is so well known and established that a sentence comprehension test, the Token Test 49, is widely used in the clinic to identify patients with aphasia among individuals with brain lesions. Although patients with inferior frontal lesions and Brocas aphasia usually have mildly impaired speech comprehension50, some of them may present without comprehension impairments in clinical tests of single-word comprehension. However, a good performance on tests developed to detect profound deficits should not be taken as evidence of spared functions. If speech is speeded up and overlaid by noise, as is often the case in real life, singleword comprehension is impaired in patients with a left inferior frontal lesion and Brocas aphasia51 and, even under optimal perceptual conditions, single-word comprehension is delayed51 and the normal activation in response to phonologically similar words is reduced52,53. These studies show that lesions in inferior frontal and premotor areas compromise the patients ability to comprehend meaningful words. Understanding single words requires at least two types of information: phonological information about relevant acoustic features of speech sounds, which is required for speech perception; and information about the meaning of words, which is required for semantic comprehension. In actionperception circuits, the activated action part sends back excitatory projections to the auditoryperception part, leading to facilitation; lesions in inferior frontal areas impair the speech perception process because they degrade this feedback activation and hinder the circuit in becoming fully active (BOX 1). At the phonological level, this mechanism can be probed in experiments assessing the discrimination and identification of phonemes or syllables in isolation. Interestingly, the discrimination and identification of speech
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sounds and syllables is impaired in aphasic patients with lesions in the frontal cortex 54 (BOX 1; for further discussion, see Supplementary information S2 (box)). At a more specific level, TMS of lip and tongue areas in the precentral cortex had a considerable effect on phoneme identification in people listening to consonantvowel syllables that were overlaid by noise55. Interestingly, stimulation of the tongue area increased the accuracy and speed with which tongue-related sounds were identified, but led to errors and delays in perceiving lip-related sounds. The opposite pattern arose when the lip area of the precentral cortex was stimulated: d and t sounds tended to be misheard as b and p sounds, and processing speed was increased for lip sounds but slowed for tongue sounds (FIG. 2). Together with the lesion evidence and other TMS studies15,56,57, this recent work demonstrates an essential and specific role of the premotor cortex and/or primary motor cortex in speech perception and confirms predictions of a neurobiological model of language in which action and perception mechanisms are bound together in distributed cell assemblies7,30 that include mirror neurons58. However, as we and others have argued before, these results provide only partial support for the motor theory of speech perception, which originally postulated that there is a motor system for speech processing that is functionally separate from the system for non-linguistic action processing; such modularity is difficult to reconcile with current neuroscience data indicating that the same precentral area is involved in moving the tongue and in pronouncing a t sound37,44,45,55 (FIG. 2).
Category-specific semantic circuits Contrasting with the relatively focused perisylvian areas involved in speech perception, a wide range of additional cortical areas has been found to be active during semantic comprehension36,59. As, in one view, the meaning of a word is the object it relates to60, the area that links words to their meanings was sought in the middle and inferior temporal cortex, where auditory language areas and the visual stream for object processing converge. Specific inferior temporal areas are indeed activated by words conveying different kinds of visual information (for example, round versus brown)6164. However, the visual system and adjacent areas are not the only brain regions that processes objectrelated information about word meaning. For example, words related to odours (for example, cinnamon) activate olfactory
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brain areas more strongly than do control words65, without drawing specifically on the middle or inferior temporal cortex. A similar point has been made about words that are semantically related to sounds (for example, telephone), which strongly activate superior temporal auditory areas even if presented in written form131. These and similar results confirm that there is semantic activation in perceptual areas and adjacent cortices where information from different modalities converges59,61,66,67. Notably, local activation differences in perceptual brain systems, such as the visual and olfactory areas, reflect semantic differences in word meaning (for example, relating to object or odour information, respectively)7,61,68,69. However, the meaning of many types of words is not related to objects or sensations but to actions60. For example, the processing of action-related words such as grasp has a functional correlate in the activation of hand representation areas in the premotor and motor cortex, as has been shown using various imaging methods62,70,71. Even fine-grained semantic differences between action-related words are manifest in motor activation. Words referring to actions preferentially performed with a particular part of the body (for example, lick, pick and kick) activate motor and premotor areas in a somatotopic manner 72,73. Similar activations were reported for action phrases and sentences74,75, even abstract ones (for example, she grasped the idea)76. This somatotopy of action semantics that aspects of the meaning of action-related verbs and sentences can be read from brain activation maps suggests that the motor system contains topographically specific semantic circuits for fine-grained action word categories (BOX 2). Note that semantic links to the motor system have been shown only for words related to actions that the individuals typically can perform themselves; such semantic motor links are absent for non-human actions (for example, barking and tail-waggling) and may not occur in subjects who cannot perform an action owing to a neurological disease. Neurophysiological (electroencephalography and magnetoencephalography) studies of the time course of the processing of action-related words showed rapid activation of motor regions in response to actionrelated words and early somatotopic mapping of word meaning. This activation occurred 100250 ms after the information needed to identify a stimulus word was present that is, after the onset of presentation of written words and after the word recognition point77

of spoken words7880. As the earliest brain responses indexing the comprehension of word and sentence meaning occur at the same time81,82, this early meaning-related motor system activation is probably a manifestation of semantic processing rather than a process that follows meaning comprehension11. Whether actionperception circuits are necessary for semantic processing can be investigated using neuropsychological methods that explore the effect of activity changes in the cortex on the behaviour of individuals who have acquired language normally. A wealth of studies on categoryspecific deficits indicate that the frontal (motor) cortex and the temporo-occipital (sensory) cortex contribute to different degrees to the processing of noun categories for example, tool words (which relate to the actions that the tools are used for) and animal names (which lack an action relationship)83,84. Data from patients with stroke-induced lesions in inferior frontal or temporal areas indicate a double dissociation between processing action-related verbs and object-related nouns8489. Processing of action-related verbs is also impaired specifically in patients with degenerative brain diseases that affect the motor system or its direct vicinity, including motor neuron disease90, Parkinsons disease91,92 and the frontal variant of frontotemporal dementia93. These selective nounverb deficits can be interpreted in the context of an action perception model: most, although certainly not all, verbs are semantically related to actions, whereas many nouns tend to relate to object information that is available through the visual modality (for data and discussion, see REF. 94). It has been argued that the activation of inferior frontal areas in response to hearing action-related verbs might be unrelated to the comprehension of action-related aspects of the words meanings95; however, patients with motor neuron disease or lesions in the left inferior frontal cortex show parallel impairments in processing action-related verbs and in grouping action-related pictures according to semantic similarity 90,96,97. These results show that the inferior frontal cortex is necessary for the processing of action-related concepts and action-related verbs. The crucial role of the motor system for semantic processing is most clearly shown in studies using well-matched subcategories of action-related words that only differ minimally in the action types to which they refer. In a TMS study in which hand and leg representations of the motor cortex were stimulated, the subjects showed
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Box 2 | Actionperception circuits for semantic processing: models, brain activation and vulnerability to lesions a b

40 15 Spoken-word form Colour-related word Shape-related word 0

Face-related word

Arm-related word

Leg-related word

c
Awg d-prime value

4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 Colour Shape Face Arm

Colour-related word

Shape-related word

Face-related word

Arm-related word

Computational modelling, brain activation experiments and neuropsychological patient studies provide converging support for category-specific semantic circuits. Part a of the figure shows a model of actionperception circuits for spoken words and their meaning. Word-related circuits (shown in grey in the figure, part a) are located in the perisylvian language cortex, especially inferior frontal and superior temporal areas, and are strongly lateralized to the dominant left hemisphere (see also BOX 1). The learned, arbitrary links between the form of words and their meanings are provided by the coupling between these word-related circuits and semantic actionperception circuits (illustrated by different colours in the other brain diagrams in part a). The higher-order assemblies (including both word formand meaning-related circuits) are specific to the semantic category and store information about the actions and objects that the words are typically used to describe. Semantic circuits of words related to actions that are preferentially performed by moving the face (shown in green), arms (shown in red), and legs (shown in purple) involve neurons in somatotopically ordered sections of the motor and premotor cortex. Words conveying information about the colour (shown in blue) and shape (shown in orange) of objects are based on semantic circuits involving different parts of the inferior temporal stream of object processing. Results of event-related functional MRI studies (see the figure, part b), confirm this model of semantic circuits: perceiving colour specifically activates the anterior parahippocampal gyrus and fusiform gyrus (shown in blue in the top panel), whereas presentation of matched shape words sparks activity in the fusiform, middle temporal and dorsolateral prefrontal cortex63 (shown in orange). The numbers in the images represent the y-axis coordinates of each slice in Montreal Neurological

Institute (MNI)-standardized brain space. Understanding action-related words that refer to the face (such as talk or lick; shown in green), arm Nature Reviews | Neuroscience (such as grasp or pick; shown in red) and leg (such as walk or kick; shown in purple) activate somatotopic areas in the motor and premotor cortex (see the image on the right in the lower panel of part b), which are also active when subjects move these body parts (see the partly hidden image)79. Further support for the semantic circuit model comes from studies in patients. Category-specific actionperception circuits explain the impairment differences in the recognition of words from specific semantic categories in patients with semantic dementia. Because this disease affects the temporal pole and, with further progression of the disease, the adjacent frontotemporal cortex (as indicated schematically in the brain diagrams shown in part c of the figure), the actionperception model predicts that face- and colour-related semantic circuits, which reach into these areas, will be impaired more than other semantic networks. The diagram on the left presents the performance of patients with semantic dementia (red bars) and healthy control participants (blue bars) in a lexical decision task. In agreement with the prediction, the patients, who suffer from a severe and general semantic impairment66, were found to have more pronounced deficits in processing face- and colour-related words than in processing arm- and shape-related words120. The consistency between model predictions, neuroimaging results and neuropsychological deficits suggests an important role for category-specific actionperception circuits in semantic processing. Part b (top panel) is reproduced, with permission, from REF. 63 (2006) Oxford Journals. Part b (lower panel) is reproduced, with permission, from REF. 72 (2004) Cell Press. Histogram in part c is reproduced, with permission, from REF. 120 (2009) MIT Press.

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facilitation of concordant action-related word types: they responded more quickly to arm action-related words (for example, grasp) in a lexical decision task when the hand area was stimulated, whereas stimulation of the leg motor cortex accelerated the processing of words referring to leg actions (for example, walk)98. Thus, neuron populations in motor systems have an effect on action-related word recognition, and this effect depends on word meaning. A recent neuropsychological study found similar dissociations between fine-grained semantic categories in patients with the pronounced and specific semanticconceptual deficit known as semantic dementia (BOX 2). Together, these results provide further evidence that actionperception circuits are necessary for, and make an important contribution to, semantic processing.
Grasping the grammar of actions The questions that pertain to phonological and semantic processes can also be applied to the specifically human linguistic ability to use and understand a potentially unlimited set of sentences: is grammar processing, like the processing of phonology and semantics, supported by actionperception circuits that span inferior-frontal and superior-temporal areas of the cortex? If so, are the actionrelated circuits in the inferior-frontal cortex important for grammatical understanding that is, for extracting information from the syntactic structure of sentences? Neuroimaging research confirms that Brocas region (BA 44 or pars opercularis and BA 45 or pars triangularis) in the inferior frontal cortex and Wernickes region in the superior temporal cortex are key areas of grammar processing: they are more strongly active in response to complex sentences than to simple control sentences, and they are also strongly active in response to ungrammatical word strings99103. Lesion studies have also revealed the necessary role of Brocas area and adjacent perisylvian sites for grammar processing. Important evidence came from patients with agrammatism a grammar processing deficit that is characteristic of Brocas aphasia104. Although agrammatism frequently occurs after lesions in the inferior frontal cortex including Brocas area, a systematic study showed that lesions anywhere in the left perisylvian cortex can cause this deficit 105. In addition to deficits in the production of words and affixes with predominantly grammatical function and grammatically correct sentences, the patients typically show an agrammatical comprehension
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Box 3 | Brain mechanisms of syntax a challenge for neuroscience

How the mechanisms for processing discrete grammatical rules or, alternatively, probabilistic syntactic regularities, are organized in the brain and how they develop in ontogeny has been studied with network simulations, but remains a matter of debate121123. One class of neural network model extracts information about the combination of string elements from sentences. As the networks did not seem to develop or use mechanisms that were functionally similar to linguistic rules, researchers concluded that no rules operate in the processing of language124. However, when features of cortical structure and function (including sequence-sensitive cells, excitatory connections between neurons in the same area, sparse coding and unsupervised Hebbian learning) were incorporated into the network, grammar circuits emerged as a consequence of learning. These circuits served functions similar to rules113, supporting the idea that language processing in neuronal circuits involves the application of linguistic rules123. The built-in structural features of these networks imply that some a priori combinatorial knowledge is available at the onset of learning, a claim supported by differences in brain activation that occur in response to structurally different syllable sequences in newborn babies125. The mechanisms underlying grammar and syntax may be domain general, applying to every kind of action. Indeed, similar to phrases in sentences, basic body acts are joined in action chains to form a meaningful goal-directed action sequence (drinking from a cup requires grasping, lifting, turning and so on). Importantly, even very complex types of syntactic structures have an equivalent in other action domains. The hierarchical structure of embedded or nested sentences is paralleled, for example, in music and bodily interaction111,126, as the following examples illustrate: a centreembedded sentence (The man {whom the dog chased} ran away) has the same nested structure as a standard jazz piece (theme {solos} modified theme) and complex everyday action sequences (open door {switch on light} close door). In each case, a superordinate sequence surrounds a nested action or sequence (in the inner parentheses). Because language, music and body action have similar hierarchical syntactic structures, the principal underlying brain mechanisms might be the same58. The domain-general role of Brocas area, especially Brodmann area 44, in the hierarchical structuring of actions (see the main text) could be derived from its evolutionarily earlier premotor functions in action control and action recognition. It will be a fruitful target of future research to clarify how syntactic processes and representations emerge from actionperception circuits and which properties of the human brain are important for building syntactic circuits127.

deficit: their impairment in understanding single words is only mild (see the discussion above), but they have great difficulty in aligning scrambled words into a sentence or in understanding complex sentences for example, passive (but not active) sentences and object-relative (but not subject-relative) sentences89,106. The important role of Brocas area in understanding the grammar of sentences is paralleled in non-linguistic modalities107. Together with their syntactic deficits, patients with lesions in the inferior frontal cortex have difficulty in ordering pictures into well-known sequences of actions89. Similar results have been shown in healthy individuals during temporary inactivation of Brocas area by TMS108. The inferior frontal area also provides a common substrate for processing grammatical sentences and familiar musical sequences109111. In summary, brain activation and lesion data confirm that Brocas area in the inferior frontal cortex is active during, and is necessary for, the production and understanding of complex syntactic structures that are immanent in sequences of body actions, musical tunes and grammatical word strings58. Why are inferior frontal cortex and superior temporal areas important for

understanding grammar? We propose that the brains grammar network evolved in areas in which actionperception circuits for hand, mouth and articulator actions were already established that is, in the left perisylvian cortex. This includes premotor area BA 44 (REF. 58), which is probably the human homologue of monkey area F5 (REF. 13). Neurons that respond specifically to sequences of words may also be present in this area; note that sequence-specific neurons have been found in a range of animals (for example, see REF. 112), making it likely that the same mechanisms operate on language in humans. Neurocomputational work shows that word sequence processors are joined together (by learning) into circuits that provide a basis for higher-level syntactic structures. These circuits link syntactic categories (such as articles, nouns and verbs) to each other 113. Even complex types of syntactic structures, such as hierarchical nesting (BOX 3), might engage word and sequence processors in the left perisylvian cortex. Consistent with this conjecture, hearing hierarchically nested sequences activates the posterior superior temporal cortex together with the pars opercularis of Brocas area, which are linked by the arcuate fascicle114,115. These results further confirm the important role
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of the inferior frontal and superior temporal areas in grammar processing at different levels. Further deciphering the neuronal wiring that enables the human brain to support grammar is a major target of future research.
Conclusions Language processing is based on neuronal circuits that reciprocally connect action systems of the brain with perceptual circuits. There is agreement that, in the healthy brain, the production of phonemes, words and sentences requires continuous auditory and somatosensory feedback12. Recent research has answered the complementary and important question about the functional contributions of the action system to perception and comprehension. At the level of speech sound processing, functional changes in the motor and premotor cortex lead to phonological deficits in patients, and experimentally activating specific parts of these brain areas affects the recognition of specific speech sounds. In the domain of processing word meaning, the recognition of specific semantic word categories can be influenced by magnetic stimulation of the motor system. In addition, focal brain lesions of frontotemporal systems lead to specific deficits in processing semantic word types that are consistent with predictions from a model of category-specific semantic actionperception circuits. Syntactic processing of sentences, and also processing the syntax of sequential

actions more generally, requires functionality of the perisylvian cortex, especially inferior frontal areas. These results show the important contribution of motor systems to language perception and comprehension at different levels. They strongly support a new, more general idea of active perception in which, for example, listening instead of hearing and looking instead of seeing are the cross-modal products of an intention-driven sensorimotor system laid down in the brain at the neuronal circuit level. Why should the motor system be involved in perception if the brain is provided with exquisite sensory areas? Of key importance to this question are sensorimotor neurons in the frontocentral cortex: sensorimotor circuits, established (in this linguistic context) as a consequence of learning, provide automatic coupling between stimulus features and the actions that produce these sensory features. By way of recurrent connections, especially through the arcuate fascicle, the action circuits feed back to the auditory cortex, thereby enhancing the perceptual salience of specific sensory stimuli. An analogous mechanism probably forms the basis of visuospatial attention and the generation of peripersonal space8. The evidence summarized here shows that actionperception links are also effective in language understanding. These findings have wider implications for brain theory. In particular, they question

general models of bottom-up sensory processing that do not acknowledge the influence of action-related information on the cognitive perception process. Although bottom-up models hold true for early stages of perception1, they do not account for higher-order perceptual processing and understanding as it becomes relevant in cognition, especially language. Crucially, bottom-up approaches do not explain why the frontocentral action system has a profound effect on speech sound perception (FIG. 2), semantic understanding (BOX 2) and syntactic parsing. Double dissociations between perceptual and action-related abilities caused by brain lesions are accounted for by the functional structure of action perception circuits (BOX 1). Proposals that actionperception interactions are optional or only effective in cases of perceptual challenge or high attention45, are countered by observations that the motor system is active even during attentional distraction from easy-to-perceive linguistic stimuli116,117. Thus, actionperception circuits with their sensorimotor cells, including mirror neurons, offer a mechanism for language processing and understanding and for interactive sign and information processing more generally. The theoretical framework presented in this Perspective centres on the neurobiological mechanisms on which language is based. The empirical evidence for active perception of language is provided by

Glossary
Motor cortex
The portion of the frontal cortex that controls movements and is therefore classically considered an output area of the cortex. It includes primary motor, premotor and supplementary motor areas.

Semantics
Scientific discipline studying the meaning of words and, in a wider use of the term, meaning in general. The term is also used as a synonym of meaning.

Brocas area Sensorimotor neuron

A neuron that is activated both by sensory stimulation sometimes through various modalities and during action execution. Mirror neurons and canonical neurons are special types of sensorimotor neurons. The posterior part of the inferior frontal gyrus. It includes the cytoarchitectonically defined Brodmann area 44 (BA 44) and BA 45 and is involved in speech production.

in representations in adjacent brain regions. Phonological somatotopy refers to the somatotopic representation of speech sounds in the motor areas of the articulator that produced the speech sounds. Semantic somatotopy is the mapping of action-related words to the motor areas representing the body parts typically involved in executing the action.

Transcranial magnetic stimulation

A non-invasive method for focal cortical stimulation by means of a coil positioned on the scalp. It delivers brief, strong electric pulses. These create a local magnetic field, which induces a current in the surface of the cortex that temporarily changes local neural activity.

Phoneme Mirror neuron

A neuron that activates during action execution and during the observation of another individual performing a similar action. Some mirror neurons also fire during listening to action-related sounds. A speech sound and smallest unit of speech that can be used to distinguish between meaningful words in a given language.

Perisylvian cortex
The brain region surrounding the sylvian fissure which, in the left hemisphere of almost all right-handed people and in most left-handed people, is most relevant for language processing. It includes the posterior inferior frontal cortex, the superior temporal cortex, inferior parietal areas, the insula and cortico-cortical fibre bundles.

Neuropsychology
A scientific discipline studying the effects on behaviour of changes in neuronal function caused, for example, by a brain lesion, magnetic stimulation, drugs or sensory stimulation.

Syntactic
Relating to the rules of syntax the grammatical arrangement of words and phrases in a sentence, which affects relationships of meaning. For example, changing the placement of a word or phrase can change the meaning.

Wernickes region
The posterior perisylvian cortex, originally identified by the PolishGerman neurologist Carl Wernicke as the area necessary for speech comprehension. Although definitions vary, Brodmann area 22 in the superior temporal cortex is usually included.

Phonological
Relating to the scientific discipline of phonology, which studies the sound structure of languages. The term is also used to refer to the sound structure of a language itself.

Somatotopy
A property of motor and somatosensory cortices whereby the spatial organization of adjacent body parts is preserved

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neurophysiological and neuropsychological studies and suggests a general model of how the brain works. The implications of this framework for linguistic theory are obvious, as brain correlates of linguistic constructs including phonetic-distinctive features, semantic categories and syntactic structures are related to mechanistic neuronal circuits, their cortical distributions, mutual interactions, interdependence and activation dynamics. We view this new approach as an integration point at which linguistic and neuroscience experiment and theory converge.
Friedemann Pulvermller is at the Medical Research Council, Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge, CB2 2EF, UK. Luciano Fadiga is at the University of Ferrara, Department of Human Physiology, via Fossato di Mortara 17/19, 44100 Ferrara, Italy, and the Italian Institute of Technology, via Morego 30, 16163, Genova, Italy. e-mails: friedemann.pulvermuller@mrc-cbu. cam.ac.uk; fdl@unife.it doi:10.1038/nrn2811 Published online 9 April 2010 1.
2. 3. Hubel, D. Eye, Brain, and Vision (Scientific American Library, New York, 1995). Fodor, J. A. The Modulatity of Mind (MIT Press, Cambridge, Massachusetts, 1983). Shallice, T. From Neuropsychology to Mental Structure (Cambridge University Press, New York, 1988). Rizzolatti, G., Fadiga, L., Gallese, V. & Fogassi, L. Premotor cortex and the recognition of motor actions. Brain Res. Cogn. Brain Res. 3, 131141 (1996). Kohler, E. et al. Hearing sounds, understanding actions: action representation in mirror neurons. Science 297, 846848 (2002). Braitenberg, V. & Schz, A. Cortex: Statistics and Geometry of Neuronal Connectivity (Springer, Berlin, 1998). Pulvermller, F. Words in the brains language. Behav. Brain Sci. 22, 253336 (1999). Fadiga, L., Fogassi, L., Gallese, V. & Rizzolatti, G. Visuomotor neurons: ambiguity of the discharge or motor perception? Int. J. Psychophysiol. 35, 165177 (2000). Jeannerod, M. Motor Cognition: What Actions Tell to the Self (Oxford University Press, Oxford, 2006). Rizzolatti, G. & Craighero, L. The mirror-neuron system. Annu. Rev. Neurosci. 27, 169192 (2004). Pulvermller, F. Brain mechanisms linking language and action. Nature Rev. Neurosci. 6, 576582 (2005). Guenther, F. H., Ghosh, S. S. & Tourville, J. A. Neural modeling and imaging of the cortical interactions underlying syllable production. Brain Lang. 96, 280301 (2006). Petrides, M., Cadoret, G. & Mackey, S. Orofacial somatomotor responses in the macaque monkey homologue of Brocas area. Nature 435, 12351238 (2005). Fadiga, L., Fogassi, L., Pavesi, G. & Rizzolatti, G. Motor facilitation during action observation: a magnetic stimulation study. J. Neurophysiol. 73, 26082611 (1995). Fadiga, L., Craighero, L., Buccino, G. & Rizzolatti, G. Speech listening specifically modulates the excitability of tongue muscles: a TMS study. Eur. J. Neurosci. 15, 399402 (2002). Pulvermller, F., Shtyrov, Y. & Ilmoniemi, R. J. Spatiotemporal patterns of neural language processing: an MEG study using minimum-norm current estimates. Neuroimage 20, 10201025 (2003). 17. Fogassi, L. et al. Parietal lobe: from action organization to intention understanding. Science 308, 662667 (2005). 18. Tomasello, M. & Call, J. in The Gestural Communication of Apes and Monkeys (eds Call, J. & Tomasello, M.) 221239 (Lawrence Erlbaum Associates, Mahwah, 2007). 19. Werker, J. F. & Tees, R. C. Influences on infant speech processing: toward a new synthesis. Annu. Rev. Psychol. 50, 509535 (1999). 20. Mampe, B., Friederici, A. D., Christophe, A. & Wermke, K. Newborns cry melody is shaped by their native language. Curr. Biol. 19, 19941997 (2009). 21. Cheour, M. et al. Development of language-specific phoneme representations in the infant brain. Nature Neurosci. 1, 351353 (1998). 22. de Boysson-Bardies, B. & Vihman, M. M. Adaptation to language: evidence from babbling and first words in four languages. Language 67, 297319 (1991). 23. Locke, J. L. The Childs Path to Spoken Language (Harvard University Press, Cambridge, Massachusetts, 1993). 24. Braitenberg, V. & Pulvermller, F. Entwurf einer neurologischen Theorie der Sprache. Naturwissenschaften 79, 103117 (1992) (in German). 25. Catani, M., Jones, D. K. & Ffytche, D. H. Perisylvian language networks of the human brain. Ann. Neurol. 57, 816 (2005). 26. Saffran, J. R., Aslin, R. N. & Newport, E. L. Statistical learning by 8-month-old infants. Science 274, 19261928 (1996). 27. Hauser, M. D., Newport, E. L. & Aslin, R. N. Segmentation of the speech stream in a non-human primate: statistical learning in cotton-top tamarins. Cognition 78, B53B64 (2001). 28. Bishop, D. V., Brown, B. B. & Robson, J. The relationship between phoneme discrimination, speech production, and language comprehension in cerebral-palsied individuals. J. Speech Hear Res. 33, 210219 (1990). 29. Westermann, G. & Reck Miranda, E. A new model of sensorimotor coupling in the development of speech. Brain Lang. 89, 393400 (2004). 30. Garagnani, M., Wennekers, T. & Pulvermller, F. A neuroanatomically-grounded Hebbian learning model of attention-language interactions in the human brain. Eur. J. Neurosci. 27, 492513 (2008). 31. Pulvermller, F. & Preissl, H. A cell assembly model of language. Network Comput. Neur. Syst. 2, 455468 (1991). 32. Paus, T., Perry, D. W., Zatorre, R. J., Worsley, K. J. & Evans, A. C. Modulation of cerebral blood flow in the human auditory cortex during speech: role of motor-to-sensory discharges. Eur. J. Neurosci. 8, 22362246 (1996). 33. Watkins, K. E., Strafella, A. P. & Paus, T. Seeing and hearing speech excites the motor system involved in speech production. Neuropsychologia 41, 989994 (2003). 34. Zatorre, R. J., Evans, A. C., Meyer, E. & Gjedde, A. Lateralization of phonetic and pitch discrimination in speech processing. Science 256, 846849 (1992). 35. Wilson, S. M., Saygin, A. P., Sereno, M. I. & Iacoboni, M. Listening to speech activates motor areas involved in speech production. Nature Neurosci. 7, 701702 (2004). 36. Vigneau, M. et al. Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing. Neuroimage 30, 14141432 (2006). 37. Pulvermller, F. et al. Motor cortex maps articulatory features of speech sounds. Proc. Natl Acad. Sci. USA 103, 78657870 (2006). 38. Uppenkamp, S., Johnsrude, I. S., Norris, D., Marslen-Wilson, W. & Patterson, R. D. Locating the initial stages of speech-sound processing in human temporal cortex. Neuroimage 31, 12841296 (2006). 39. Scott, S. K., McGettigan, C. & Eisner, F. A little more conversation, a little less action candidate roles for the motor cortex in speech perception. Nature Rev. Neurosci. 10, 295302 (2009). 40. Diesch, E., Eulitz, C., Hampson, S. & Ross, B. The neurotopography of vowels as mirrored by evoked magnetic field measurements. Brain Lang. 53, 143168 (1996). 41. Obleser, J. et al. Vowel sound extraction in anterior superior temporal cortex. Hum. Brain Mapp. 27, 562571 (2006). 42. Fry, D. B. in The Genesis of Language (eds Smith, F. & Miller, G. A.) 187206 (MIT Press, Cambridge, Massachusetts, 1966). 43. Liberman, A. M., Cooper, F. S., Shankweiler, D. P. & Studdert-Kennedy, M. Perception of the speech code. Psychol. Rev. 74, 431461 (1967). 44. Galantucci, B., Fowler, C. A. & Turvey, M. T. The motor theory of speech perception reviewed. Psychon. Bull. Rev. 13, 361377 (2006). 45. Lotto, A. J., Hickok, G. S. & Holt, L. L. Reflections on mirror neurons and speech perception. Trends Cogn. Sci. 13, 110114 (2009). 46. Lichtheim, L. On aphasia. Brain 7, 433484 (1885). 47. Broca, P. Remarques sur la sige de la facult de la parole articule, suivies dune observation daphmie (perte de parole). Bull.Soc. Anat. 36, 330357 (1861) (in French). 48. Wernicke, C. Der aphasische Symptomencomplex. Eine psychologische Studie auf anatomischer Basis (Kohn und Weigert, Breslau, 1874) (in German). 49. De Renzi, E. & Vignolo, L. The token test: a sensitive test to detect receptive disturbances in aphasics. Brain 85, 665678 (1962). 50. Rosenbek, J. C., LaPointe, L. L. & Wertz, R. Aphasia: A Clincial Approach (College-Hill Press, Boston, 1995). 51. Moineau, S., Dronkers, N. F. & Bates, E. Exploring the processing continuum of single-word comprehension in aphasia. J. Speech Lang. Hear. Res. 48, 884896 (2005). 52. Yee, E., Blumstein, S. E. & Sedivy, J. C. Lexicalsemantic activation in Brocas and Wernickes aphasia: evidence from eye movements. J. Cogn. Neurosci. 20, 592612 (2008). 53. Utman, J. A., Blumstein, S. E. & Sullivan, K. Mapping from sound to meaning: reduced lexical activation in Brocas aphasics. Brain Lang. 79, 444472 (2001). 54. Basso, A., Casati, G. & Vignolo, L. A. Phonemic identification defect in aphasia. Cortex 13, 8595 (1977). 55. DAusilio, A. et al. The motor somatotopy of speech perception. Curr. Biol. 19, 381385 (2009). 56. Meister, I. G., Wilson, S. M., Deblieck, C., Wu, A. D. & Iacoboni, M. The essential role of premotor cortex in speech perception. Curr. Biol. 17, 16921696 (2007). 57. Mottonen, R. & Watkins, K. E. Motor representations of articulators contribute to categorical perception of speech sounds. J. Neurosci. 29, 98199825 (2009). 58. Fadiga, L., Craighero, L. & DAusilio, A. Brocas area in language, action, and music. Ann. NY Acad. Sci. 1169, 448458 (2009). 59. Binder, J. R., Desai, R. H., Graves, W. W. & Conant, L. L. Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. Cereb. Cortex 19, 27672796 (2009). 60. Wittgenstein, L. Philosophical Investigations (Blackwell Publishers, Oxford, 1953). 61. Damasio, H., Grabowski, T. J., Tranel, D., Hichwa, R. D. & Damasio, A. R. A neural basis for lexical retrieval. Nature 380, 499505 (1996). 62. Martin, A., Wiggs, C. L., Ungerleider, L. G. & Haxby, J. V. Neural correlates of category-specific knowledge. Nature 379, 649652 (1996). 63. Pulvermller, F. & Hauk, O. Category-specific processing of color and form words in left frontotemporal cortex. Cereb. Cortex 16, 11931201 (2006). 64. Simmons, W. K. et al. A common neural substrate for perceiving and knowing about color. Neuropsychologia 45, 28022810 (2007). 65. Gonzalez, J. et al. Reading cinnamon activates olfactory brain regions. Neuroimage 32, 906912 (2006). 66. Patterson, K., Nestor, P. J. & Rogers, T. T. Where do you know what you know? The representation of semantic knowledge in the human brain. Nature Rev. Neurosci. 8, 976987 (2007). 67. Wise, R. J. et al. Noun imageability and the temporal lobes. Neuropsychologia 38, 985994 (2000).

4.

5.

6.

7. 8.

9. 10. 11.

12.

13.

14.

15.

16.

NATURE REVIEWS | NEUROSCIENCE 2010 Macmillan Publishers Limited. All rights reserved

VOLUME 11 | MAY 2010 | 359

PERSPECTIVES
68. Barsalou, L. W. Grounded cognition. Annu. Rev. Psychol. 59, 617645 (2008). 69. Martin, A. The representation of object concepts in the brain. Annu. Rev. Psychol. 58, 2545 (2007). 70. Kiefer, M. Perceptual and semantic sources of category-specific effects: event-related potentials during picture and word categorization. Mem. Cognit. 29, 100116 (2001). 71. Pulvermller, F., Kherif, F., Hauk, O., Mohr, B. & Nimmo-Smith, I. Cortical cell assemblies for general lexical and category-specific semantic processing as revealed by fMRI cluster analysis. Hum. Brain Mapp. 30, 38373850 (2009). 72. Hauk, O., Johnsrude, I. & Pulvermller, F. Somatotopic representation of action words in the motor and premotor cortex. Neuron 41, 301307 (2004). 73. Kemmerer, D., Castillo, J. G., Talavage, T., Patterson, S. & Wiley, C. Neuroanatomical distribution of five semantic components of verbs: evidence from fMRI. Brain Lang. 107, 1643 (2008). 74. Tettamanti, M. et al. Listening to action-related sentences activates fronto-parietal motor circuits. J. Cogn Neurosci. 17, 273281 (2005). 75. Aziz-Zadeh, L., Wilson, S. M., Rizzolatti, G. & Iacoboni, M. Congruent embodied representations for visually presented actions and linguistic phrases describing actions. Curr. Biol. 16, 18181823 (2006). 76. Boulenger, V., Hauk, O. & Pulvermller, F. Grasping ideas with the motor system: semantic somatotopy in idiom comprehension. Cereb. Cortex 19, 19051914 (2009). 77. Marslen-Wilson, W. D. Functional parallelism in spoken word-recognition. Cognition 25, 71102 (1987). 78. Pulvermller, F., Hrle, M. & Hummel, F. Neurophysiological distinction of verb categories. Neuroreport 11, 27892793 (2000). 79. Hauk, O. & Pulvermller, F. Neurophysiological distinction of action words in the fronto-central cortex. Hum. Brain Mappp. 21, 191201 (2004). 80. Pulvermller, F., Shtyrov, Y. & Ilmoniemi, R. J. Brain signatures of meaning access in action word recognition. J. Cogn. Neurosci. 17, 884892 (2005). 81. Hauk, O., Davis, M. H., Ford, M., Pulvermller, F. & Marslen-Wilson, W. D. The time course of visual word recognition as revealed by linear regression analysis of ERP data. Neuroimage 30, 13831400 (2006). 82. Sereno, S. C., Brewer, C. C. & ODonnell, P. J. Context effects in word recognition: evidence for early interactive processing. Psychol. Sci. 14, 328333 (2003). 83. Warrington, E. K. & McCarthy, R. A. Categories of knowledge: further fractionations and an attempted integration. Brain 110, 12731296 (1987). 84. Gainotti, G. A metanalysis of impaired and spared naming for different categories of knowledge in patients with a visuo-verbal disconnection. Neuropsychologia 42, 299319 (2004). 85. Miceli, G., Mazzucchi, A., Menn, L. & Goodglass, H. Contrasting cases of italian agrammatic aphasia without comprehension disorders. Brain Lang. 19, 6597 (1983). 86. Damasio, A. R. & Tranel, D. Nouns and verbs are retrieved with differently distributed neural systems. Proc. Natl Acad. Sci. USA 90, 49574960 (1993). 87. Daniele, A., Giustolisi, L., Silveri, M. C., Colosimo, C. & Gainotti, G. Evidence for a possible neuroanatomical basis for lexical processing of nouns and verbs. Neuropsychologia 32, 13251341 (1994). 88. Neininger, B. & Pulvermller, F. Word-category specific deficits after lesions in the right hemisphere. Neuropsychologia 41, 5370 (2003). 89. Fazio, P. et al. Encoding of human action in Brocas area. Brain 132, 19801988 (2009). 90. Bak, T. H., ODonovan, D. G., Xuereb, J. H., Boniface, S. & Hodges, J. R. Selective impairment of verb processing associated with pathological changes in Brodmann areas 44 and 45 in the motor neurone diseasedementiaaphasia syndrome. Brain 124, 103120 (2001). 91. Cotelli, M. et al. Action and object naming in Parkinsons disease without dementia. Eur. J. Neurol. 14, 632637 (2007). 92. Boulenger, V. et al. Word processing in Parkinsons disease is impaired for action verbs but not for concrete nouns. Neuropsychologia 46, 743756 (2008). 93. Cotelli, M. et al. Action and object naming in frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration. Neuropsychology 20, 558565 (2006). 94. Pulvermller, F., Lutzenberger, W. & Preissl, H. Nouns and verbs in the intact brain: evidence from event-related potentials and high-frequency cortical responses. Cereb. Cortex 9, 498508 (1999). 95. Bird, H., Lambon-Ralph, M. A., Patterson, K. & Hodges, J. R. The rise and fall of frequency and imageability: noun and verb production in semantic dementia. Brain Lang. 73, 1749 (2000). 96. Tranel, D., Kemmerer, D., Adolphs, R., Damasio, H. & Damasio, A. R. Neural correlates of conceptual knowledge for actions. Cogn. Neuropsychol. 20, 409432 (2003). 97. Bak, T. H. et al. Clinical, imaging and pathological correlates of a hereditary deficit in verb and action processing. Brain 129, 321332 (2006). 98. Pulvermller, F., Hauk, O., Nikulin, V. V. & Ilmoniemi, R. J. Functional links between motor and language systems. Eur. J. Neurosci. 21, 793797 (2005). 99. Caplan, D. et al. Vascular responses to syntactic processing: event-related fMRI study of relative clauses. Hum. Brain Mapp. 15, 2638 (2002). 100. Just, M. A., Carpenter, P. A., Keller, T. A., Eddy, W. F. & Thulborn, K. R. Brain activation modulated by sentence comprehension. Science 274, 114116 (1996). 101. Kinno, R., Kawamura, M., Shioda, S. & Sakai, K. L. Neural correlates of noncanonical syntactic processing revealed by a picture-sentence matching task. Hum. Brain Mapp. 29, 10151027 (2008). 102. Friederici, A. D. Towards a neural basis of auditory sentence processing. Trends Cogn. Sci. 6, 7884 (2002). 103. Shtyrov, Y., Pulvermller, F., Ntnen, R. & Ilmoniemi, R. J. Grammar processing outside the focus of attention: an MEG study. J. Cogn. Neurosci. 15, 11951206 (2003). 104. Pick, A. Die agrammatischen Sprachstrungen. Studien zur psychologischen Grundlegung der Aphasielehre (Springer, Berlin, 1913) (in German). 105. Caplan, D., Hildebrandt, N. & Makris, N. Location of lesions in stroke patients with deficits in syntactic processing in sentence comprehension. Brain 119, 933949 (1996). 106. Caramazza, A. & Zurif, E. B. Dissociation of algorithmic and heuristic processes in sentence comprehension: evidence from aphasia. Brain Lang. 3, 572582 (1976). 107. Dominey, P. F., Hoen, M., Blanc, J. M. & Lelekov-Boissard, T. Neurological basis of language and sequential cognition: evidence from simulation, aphasia, and ERP studies. Brain Lang. 86, 207225 (2003). 108. Clerget, E., Winderickx, A., Fadiga, L. & Olivier, E. Role of Brocas area in encoding sequential human actions: a virtual lesion study. Neuroreport 20, 14961499 (2009). 109. Chen, J. L., Penhune, V. B. & Zatorre, R. J. Listening to musical rhythms recruits motor regions of the brain. Cereb. Cortex 18, 28442854 (2008). 110. Maess, B., Koelsch, S., Gunter, T. C. & Friederici, A. D. Musical syntax is processed in Brocas area: an MEG study. Nature Neurosci. 4, 540545 (2001). 111. Patel, A. D. Language, music, syntax and the brain. Nature Neurosci. 6, 674681 (2003). 112. Reichardt, W. & Varju, D. bertragungseigenschaften im Auswertesystem fr das Bewegungssehen. Zeitschrift fr Naturforschung 14b, 674689 (1959) (in German). 113. Pulvermller, F. & Knoblauch, A. Discrete combinatorial circuits emerging in neural networks: a mechanism for rules of grammar in the human brain? Neural Netw. 22, 161172 (2009). 114. Koechlin, E. & Jubault, T. Brocas area and the hierarchical organization of human behavior. Neuron 50, 963974 (2006). 115. Bahlmann, J., Schubotz, R. I. & Friederici, A. D. Hierarchical artificial grammar processing engages Brocas area. Neuroimage 42, 525534 (2008). 116. Pulvermller, F. & Shtyrov, Y. Language outside the focus of attention: the mismatch negativity as a tool for studying higher cognitive processes. Prog. Neurobiol. 79, 4971 (2006). 117. Pulvermller, F. & Shtyrov, Y. Spatio-temporal signatures of large-scale synfire chains for speech: MEG evidence. Cereb. Cortex 19, 7988 (2009). 118. Garagnani, M., Shtyrov, Y. & Pulvermller, F. Effects of attention on what is known and what is not: MEG evidence for functionally discrete memory circuits. Front. Hum. Neurosci. 30 Jun 2009 (doi:10.3389/ neuro.09.010.2009). 119. Wennekers, T., Garagnani, M. & Pulvermller, F. Language models based on Hebbian cell assemblies. J. Physiol. (Paris) 100, 1630 (2006). 120. Pulvermller, F. et al. The word processing deficit in Semantic Dementia: all categories are equal but some categories are more equal than others. J. Cogn. Neurosci. 1 Sep 2009 (doi:10.1162/ jocn.2009.21339). 121. Chater, N. & Manning, C. D. Probabilistic models of language processing and acquisition. Trends Cogn. Sci. 10, 335344 (2006). 122. Elman, J. L. et al. Rethinking Innateness. A Connectionist Perspective on Development (MIT Press, Cambridge, Massachusetts, 1996). 123. Marcus, G. F. The Algebraic Mind: Integrating Connectionism and Cognitive Science (MIT Press, Cambridge, Massachusetts, 2001). 124. McClelland, J. L. & Patterson, K. Rules or connections in past-tense inflections: what does the evidence rule out? Trends Cogn. Sci. 6, 465472 (2002). 125. Gervain, J., Macagno, F., Cogoi, S., Pena, M. & Mehler, J. The neonate brain detects speech structure. Proc. Natl Acad. Sci. USA 105, 1422214227 (2008). 126. Grafton, S. T. & Hamilton, A. F. Evidence for a distributed hierarchy of action representation in the brain. Hum. Mov. Sci. 26, 590616 (2007). 127. Pulvermller, F. Brain embodiment of syntax and grammar: discrete combinatorial mechanisms spelt out in neuronal circuits. Brain Lang. 112, 167179 (2010). 128. Petrides, M. & Pandya, D. N. Distinct parietal and temporal pathways to the homologues of Brocas area in the monkey. PLoS Biol. 7, e1000170 (2009). 129. Rilling, J. K. et al. The evolution of the arcuate fasciculus revealed with comparative DTI. Nature Neurosci. 11, 426428 (2008). 130. Saur, D. et al. Ventral and dorsal pathways for language. Proc. Natl Acad. Sci. USA 105, 1803518040 (2008). 131. Kiefer, M., Sim, E. J., Herrnberger, B., Grothe, J. & Hoenig, K. The sound of concepts: four markers for a link between auditory and conceptual brain systems. J. Neurosci. 28, 1222412230 (2008).

Acknowledgements
We thank M. Garagnani, I. Laka, R. Wise, R. Moseley and three anonymous reviewers for their comments on earlier versions of this manuscript. This work is supported by the Medical Research Council (UK) (U1055.04.003.00001.01) to F.P., by the Fondazione Cassa di Risparmio di Ferrara to L.F. and by the European Community (Nestcom (NEST-2005PATH-HUM contract 043,374) to F.P. and Robot-cub, Contact, Poeticon to L.F.).

Competing interests statement

The authors declare no competing financial interests.

DATABASES
OMIM: http://www.ncbi.nlm.nih.gov/omim frontotemporal dementia | Parkinsons disease

FURTHER INFORMATION
Friedemann Pulvermullers homepages: http://www.mrc-cbu.cam.ac.uk/people/friedemann.pulvermuller; http://www.neuroscience.cam.ac.uk/directory/ profile.php?pulvermuller Luciano Fadigas homepage: http://www.iit.it/en/people.ht ml?view=profile&layout=profile&id=228

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