MirrorBot

IST-2001-35282

Biomimetic multimodal learning in a mirror neuron-based robot

Title: Functional Interaction Of Language And Action Processing: A TMS Study (Deliverable D1)

Authors: Friedemann Pulvermüller , Olaf Hauk, Vadim Nikulin and Risto J. IlmoniemiCovering period 1.6.2002-1.6.2003

MirrorBot Report 8

Report Version: 1

Report Preparation Date: 1. June 2002

Classification: Restricted

Contract Start Date: 1st June 2002 Duration: Three Years

Project Co-ordinator: Professor Stefan Wermter

Partners: University of Sunderland, Institut National de Recherche en Informatique et en Automatique at Nancy, Universität Ulm, Medical Research Council at Cambridge, Università degli Studi di Parma

Table of Contents

0. ABSTRACT 2

1. INTRODUCTION 3

2. MATERIAL AND METHODS 7

3. RESULTS 13

4. DISCUSSION 17

5. ACKNOWLEDGEMENT 22

6. REFERENCES 23

1

0. Abstract

Transcranial magnetic stimulation (TMS) was applied to motor areas in both hemispheres

while right-handed subjects made lexical decisions on words related to actions. Words

referring to leg actions (example: "to kick") were compared with words referring to

movements involving the arms and hands ("to pick"). Magnetic stimulation was to hand

motor areas and to dorsal sites that included the pre-motor representation of the legs.

TMS at hand and leg loci influenced the processing of arm and leg words differentially:

Stimulation at the leg loci speeded lexical decisions on leg words specifically, whereas

hand locus stimulation produced the opposite effect, faster processing of arm words

compared with leg words. A separate analysis of the effects of TMS to the dominant left

hemisphere confirmed the significant interaction of the factors stimulation site and word

group, whereas right-hemispheric stimulation failed to yield significant effects,

suggesting that left-hemisphere networks are more relevant for linking actions and words

in the brain of right-handers. The results support a distributed account of word processing

according to which information about words and the actions they refer to are stored and

processed by distributed neuronal ensembles that include mirror neurons with

somatotopic localization.

2

1. Introduction

Word processing in the context of objects and actions leads to correlated activity in

different cortical areas. If a word is frequently used when an action is performed by the

learner or by a person perceived by the learner, neurons subserving lexical processing and

those involved in processing the action become active simultaneously. This correlated

activity leads to strengthening of neuronal connections and thus to a linkage of word form

and action representations (Pulvermüller, 1999). The resulting word-related neuron

ensembles, word webs, may have distinct topographies, depending on where in the cortex

the correlated activity occurred.

The somatotopic organization of the motor and pre-motor cortex implies that actions

performed with different body parts relate to different topographic patterns of activation

in motor, pre-motor and adjacent prefrontal areas. Somatotopic organization has been

demonstrated for the primary motor cortex (Penfield and Rasmussen, 1950) and could be

revealed for more rostral frontal areas, in particular for pre-motor areas as well (He et al.,

1993; Rizzolatti et al., 2001). In the primary motor cortex, the leg representation is to a

large extent hidden in the interhemispheric sulcus, but pre-motor representations of the

legs are also present on the lateral surface of the frontal lobe, where they are located

superior and medial to the hand representation anterior to the precentral gyrus. In both the

precentral gyrus and the pre-motor areas, arm and hand movements are represented

lateral and inferior to leg movement representations. If action-related information is

woven into the cortical neuron webs representing and processing words, one may predict

that words referring to different body parts correspond to networks with different cortical

3

distributions. The action-related neurons of a word referring to a leg movement - such as

"to kick" - should be located superior and medial to those of a word related to an arm or

hand movement - as, for example, "to pick". The semantic difference between

subcategories of action words should thus be laid down in the cortical distribution of

word-related neuron webs, a hypothesis with clear implications for neurophysiological

brain research on language (Pulvermüller, 2001).

We investigated the processing of action words using Transcranial Magnetic

Stimulation (TMS), a well-established tool for scrutinizing the brain basis of cognition

and language. In recent years, TMS pulses delivered to different parts of the left

perisylvian language cortex have been shown to interfere with language processing

(Epstein, 1998; Bailey et al., 2001). Single-pulse or repetitive TMS (rTMS) of inferior

frontal sites can lead to speech arrest and specific temporary articulatory deficits

(Pascual-Leone et al., 1991; Michelucci et al., 1994; Epstein et al., 1996; Stewart et al.,

2001) and stimulation of superior temporal areas to a facilitation of naming (Mottaghy et

al., 1999; Sparing et al., 2001). Language laterality has a clear reflection in the influence

of TMS pulses to left and right perisylvian areas; only in subjects with strong language

laterality - either to the left or to the right hemisphere - unilateral TMS causes a marked

dysfunction of language processing (Knecht et al., 2002). From a linguistic perspective, it

is of particular interest that rTMS of the frontal cortex led to deficits in the processing of

one specific lexical category, namely verbs (Shapiro et al., 2001). This latter result

suggests that language functions, such as the processing of specific lexical categories, can

be monitored using TMS. Further, listening to spoken words that include phonemes

strongly involving one particular articulator – e.g. [r], which strongly involves the tongue

4

– had a facilitatory effect on the TMS-induced muscle movement of that relevant

articulator – in this case the tongue (Fadiga et al., 2002). Together, these results

document the importance of TMS as a research tool for exploring very specific brain

processes of language. It is, however, also noteworthy that TMS, as any other method in

brain science, has its limitations, most of which are due to the fact that the biophysical

mechanisms elicited by TMS pulses are not fully understood (Bailey et al., 2001;

Ruohonen and Ilmoniemi, 2002). One open question is why TMS sometimes leads to a

disruption of processes supported by the stimulated area, whereas, in other cases,

facilitatory effects were observed (Maeda et al., 2000). The direction of the effect TMS

takes is difficult to predict. More specifically, language functions have been found to be

impaired (Shapiro et al., 2001; Knecht et al., 2002) or improved (Mottaghy et al., 1999;

Sparing et al., 2001) as a result of magnetic stimulation (Epstein, 1998; Epstein et al.,

1999). It appears that stimulation amplitude, duration, frequency and the topography of

the magnetic field applied crucially influence the mode (excitation or inhibition) and the

magnitude of the effect of TMS (Pascual-Leone et al., 1999; Maeda et al., 2000; Bailey et

al., 2001; Stewart et al., 2001; Rijntjes and Weiller, 2002; Ruohonen and Ilmoniemi,

2002).

In this study, we ask whether stimulation of different motor areas has a specific

influence on the processing of arm- and leg-related action words in a lexical decision

task. If word representations in the perisylvian cortex have specific links to action

representations in motor, pre-motor, and possibly prefrontal areas controlling arm and leg

movements, stimulation of arm and leg areas should differentially influence the

processing of arm and leg words. Generally, stimulation of the hand and leg motor areas

5

should have opposite effects on the processing of hand- and leg-related words. By

choosing single-pulse TMS with moderate stimulation intensity, ~90% of the individual

motor threshold, we aimed at generating a physiological activation that could facilitate

activation in the neuronal networks targeted.

6

2. Material and Methods

Subjects: 12 subjects (mean age: 26 years, S.D. = 4.8; 5 females) participated in the

study. All were native speakers of English and all except for one were monolinguals.

Results on the Oldfield Handedness Inventory (Oldfield, 1971) indicated that all subjects

were right-handed (mean laterality quotient = 84, S.D. 25). Furthermore, all participants

had normal or corrected-to-normal vision and reported no history of neurological illness

or drug abuse. Informed consent was obtained from all subjects and they were paid for

their participation. The study was approved by the Ethics Committee of the Helsinki

University Central Hospital.

Stimuli: The stimuli were 250 letter strings, including 50 arm- and 50 leg-related

English words, 50 English distractor words and 100 pseudowords that were in accordance

with the phonotactic and orthographic rules of English. The action word groups were

matched for word-length (average lengths were 4.5 letters for arm words and 4.6 for leg

words) and standardized lexical frequency according to the CELEX database (average

word frequency for arm words was 259 and for leg words 263 occurrences per million).

A rating study was performed before the experiment. Subjects were asked to rate each

word as to whether it reminded them of actions they can perform with their hands/arms or

legs, respectively. Ratings were obtained on a seven-point scale. The results shown in

Figure 1 demonstrate that there was a clear double dissociation between the two

subcategories of action words. Words from one group were consistently reported to elicit

strongest arm/hand motor associations, with weak leg associations, whereas the other

group was characterized by strong leg (but weak arm) associations. The interaction of

7

Word group and Association type (arm/leg) was highly significant (F (1,49) = 839.00, p

< 0.001). This ascertained that arm-related words elicited stronger associations of arm

actions than leg actions, whereas the opposite pattern was seen for leg words (F > 100; p

< 0.001). Further, ratings of familiarity and imageability of the action words did not

reveal differences between the stimulus groups.

Figure 1: Association ratings of word stimuli used in this study. Words from two groups

were judged as to whether they reminded subjects of arm/hand actions (red bars) and of

leg/foot actions (blue bars), respectively.

TMS stimulation: The study was performed with the TMS device at the BioMag

Laboratory, Helsinki University Central Hospital. The magnetic pulses were biphasic

with a duration of 320 µs. A figure-of-eight coil was used in order to produce focal

cortical stimulation (Bailey et al., 2001). It consisted of two coplanar circular wings (40-

mm diameter) with 15 turns of copper wire in each. The coil was oriented so that the

induced current flow was in posterior-anterior direction during the rising phase of the

pulse.

8

The following procedure was applied for determining stimulation sites and intensities.

The subjects were seated in a comfortable chair below the montage holding the TMS coil.

The motor threshold was found separately for each hemisphere. TMS pulses were given

every 2 s. EMG responses were recorded through 2 electrodes placed next to the first

dorsal interosseous (FDI) muscle of the hand contralateral to the stimulation site. The

EMG responses were continuously monitored on a computer screen. Initially, the coil

was placed at the C3 or C4 sites of the International 10-20 system of placement of EEG

electrodes (Jasper, 1958), which are known to be close to the motor representation of the

hand (Lagerlund et al., 1994). An area around C3/C4 was monitored in steps of 5 mm to

find the largest elicited muscle response of the FDI. These points were used later as the

hand stimulation loci. The motor threshold was determined as the smallest intensity

eliciting EMGs with amplitudes of at least 50 µV in 5 out of 10 successive trials.

Ethical guidelines recommended a maximum stimulation intensity for our device and

research purpose. Within the range of intensities permitted, it was not possible to

determine the leg-areas for each individual subject, i.e., no reliable EMG responses could

be measured at a lower limb muscle (M. tibialis anterior). Previous studies also found

leg-motor areas to require higher stimulation intensity than the hand motor area (e.g.,

Chen and Garg, 2000). For targeting the leg areas, we chose that point on the line

connecting the hand stimulation locus and the vertex that was one third of this distance

away from the vertex.

At the end of the experiment, control trials were added, in which a 2-cm-thick plastic

block was placed between the TMS coil and the scalp, so that no relevant TMS of cortical

tissue could occur. This condition served to mimic the auditory and somatosensory

9

sensations produced by the mechanical vibration of the coil (Nikouline et al., 1999).

Separate control runs were performed for the left and right hemispheres, respectively.

The control experiment was run to investigate possible processing differences between

word groups in the absence of TMS.

There were two competing requirements for choosing the optimal stimulation intensity.

On the one hand, the intensity of the pulse-related click, which varies with TMS intensity,

should be kept equal for the stimulation sites, to avoid differences in inter-sensory

interference. On the other hand, different motor thresholds for different hemispheres are

likely to reflect different geometry of the skull and the brain, or of the excitability of

neuronal populations. We decided to find a compromise between these requirements by

applying the following procedure: The mean of the left- and right- hemispheric motor

thresholds were computed for each subject. The mean between this value and the actual

motor threshold was then calculated for each hemisphere, and 90% of this intensity was

chosen for stimulation at hand- and leg-loci. The motor threshold for the right hemisphere

was on average 9% above that for the left hemisphere.

Stimulation procedure: During the entire experiment, a fixation cross appeared in the

middle of the screen, which was occasionally replaced by linguistic stimuli. Word and

pseudoword stimuli were tachistoscopically presented, for 100 ms, in pseudo-random

order with a stimulus onset asynchrony of 3 s. TMS pulses were applied 150 ms after the

onset of each linguistic stimulus. Letter strings were presented in white capital letters on a

gray background in the middle of a computer screen at a distance of 2 m from the

subjects' eyes. Letter strings subtended a horizontal visual angle smaller than 4 degrees.

Subjects were instructed to fixate their eyes on the fixation cross and to respond as

10

quickly and as accurately as possible by a lip movement to words only. The usual

response was that subjects articulated the syllable "ba" or performed the corresponding

lip movement. A mouth response was chosen to prevent interference of the preparation of

the behavioral response with any putative word-elicited activation of hand or leg motor or

pre-motor areas.

For each stimulation site, two successive runs, each lasting for about 3 minutes, were

performed. The stimulus set was presented 3 times, once when stimulation was to the

left-hemispheric loci, once when the right hemisphere was stimulated, and once in the

control trials (see below). For stimulation of each hemisphere, the set of stimuli was

halved and 25 items from each word category were presented together with 50

pseudowords when TMS was delivered to the arm and leg loci, respectively. The order of

the four blocks - where stimulation was to the left hand, left leg, right hand, and right leg

areas, respectively - was counterbalanced over subjects. In the control trial performed at

the end, 25 stimuli of each word group and 50 pseudowords were presented while the coil

was placed over each hemisphere.

Recording of behavioral responses: As mentioned, subjects were instructed to respond

by brisk mouth movements. These movements were measured using two EMG

electrodes. EMG electrodes were fixed on the left below the lower lip and above the

upper lip. The ground electrode was placed on the right cheek. The signal from these

electrodes was recorded using bipolar channels of an EEG amplifier. Its input was

blocked for 10 ms during and after the pulse by a sample-and-hold technique, thus

avoiding the recording channels to be saturated by the relatively high voltages induced by

the TMS pulse (Virtanen et al., 1999). The sampling rate was 1450 Hz and the analog

11

passband 0-500 Hz.

Data analysis: An EMG response was determined in the following way. For each

participant, the average EMG amplitude was calculated. Since maximal EMG amplitudes

varied over individuals, the criterion for overt behavioral responses in single trials was

defined as the first point in time exceeding 50% of the maximum average value. The

accuracy and average response times of these responses were calculated for each word

group and subject, which were then entered into three-way Analysis of Variance

(ANOVAs) with the factors Word Group, Stimulation Site, and Hemisphere. Additional

ANOVAs were performed to separately investigate effects obtained for stimulation of the

left and right hemisphere. One-tailed t-tests were used for Planned Comparison Tests.

12

3. Results

Error rates of lexical decision responses were low in most individuals. Ten out of 12

subjects made less than 12% errors. In the 2 remaining subjects, there was substantial

EMG activity in the baseline, which resulted in an unreliable assessment of responses and

high error rates, 33% and 17% respectively. Because no reliable lexical decision

responses could be obtained through EMG measures in these subjects, their data were

excluded from further analysis.

The analysis of response accuracy revealed a significant main effect of the factor

Hemisphere (F (1,9) = 7.87, p < 0.02). In the average, more errors were made when the

left hemisphere was stimulated as compared with right-hemispheric stimulation (11.2 vs.

6.7%). There were no reliable differences between stimulation sites, or between word

groups in the analysis of response accuracy. Pseudowords, for which no response was

required, led to some false positive responses. The number of errors made on these items

did not differ reliably between stimulation of the left and right hemisphere (8.0 vs.

6.2%).

13

Figure 2: Average response speed of lexical decisions on arm- and leg-related action

words in a lexical decision task after TMS to the arm and leg loci. The diagram at the top

shows data obtained when TMS was to the dominant left hemisphere. In the diagram at

the bottom, data obtained during arm and leg stimulation over both hemispheres are

collapsed. Both interactions (Stimulation site x Word group) were significant. Asterisks

indicate significant planned comparison tests.

Average latencies obtained for subjects and word groups ranged between 450 and 800

ms, with an average of 570 ms. This is compatible with the outcome of lexical decision

14

Both Hemispheres

520540560580600

arm legstimulation site

lexi

cal d

ecis

ion

RT

(ms) arm words

leg words

**

Left Hemisphere

500520540560580600

arm legstimulation site

lexi

cal d

ecis

ion

RT

(ms) arm words

leg words

*

experiments using button press responses carried out with the left or right index finger

(see, for example, Mohr et al., 1994). The three-way ANOVA revealed a significant

interaction of the factors Word Group and Stimulation Site (F (1,9) = 9.54, p < 0.01).

Faster responses to leg than arm words were found when TMS was applied to the leg loci

(t (9) = 3.38; p < 0.02; arm words: 565; leg words: 545 ms), whereas responses to arm

words were faster than those to leg words when TMS was to the arm loci (t (9) = 7.03; p

< 0.01; arm words: 575 ms; leg words: 588 ms). In addition, stimulation of leg loci

significantly facilitated leg word processing compared with TMS of arm loci (F (1,9) =

8.23, p < 0.01). Separate analyses of left-hemispheric responses did reveal the same

cross-over interaction of Word Group and Stimulation Site (F (1,9) = 5.98, p < 0.04).

Faster responses to leg words were seen with leg area stimulation as compared with arm

words (t (9) = 10.9, p < 0.005), and the opposite effect to arm-area stimulation

approached significance (p < 0.1). There were again significantly faster responses to leg

words when stimulation was to the leg locus as compared with arm locus stimulation (F

(1,9) = 5.15, p < 0.03). No reliable differences were obtained when the effects of TMS to

the right hemisphere were analyzed separately. Figure 2 displays both significant

interactions. Overall, the arm locus stimulation tended to lead to slower lexical decision

responses, but this effect did not reach significance (F (1,9) = 2.97, p = 0.12 for the

overall analysis of TMS to both hemispheres; F (1,9) = 3.4, p = 0.10 for the analysis of

left-hemispheric TMS).

The control data obtained without TMS revealed similar response times (576 vs. 572

ms) and accuracies (8.4 vs. 9.0%) for the two groups of action words. This indicates that

the processing differences between word categories seen in the TMS conditions do not

15

relate to the acoustic or somatosensory stimulation, or to word-immanent properties, but

rather to the magnetic stimulation of cortical areas.

16

4. Discussion

Stimulation of leg and arm areas in the human cortex affected the processing of leg-

and arm-related words differentially. Lexical decision responses to leg words were faster

than those to arm words when the leg area was stimulated magnetically. Similarly, faster

processing of arm- than leg-words was present when TMS pulses were delivered to the

motor areas of the hand. Significant modulation of action word processing was found

when data from TMS of both hemispheres were analyzed together or separately for left-

hemispheric stimulation sites. These results suggest that the cortical representations of

actions and words are tightly interwoven, and that strongly connected neuronal networks

processing different kinds of action words reflect the somatotopy of the motor cortical

systems involved in performing the relevant body movements.

Left hemispheric TMS influenced lexical decision latencies significantly and

specifically, but no comparable effects were apparent after stimulation of the right

hemisphere. All subjects were strongly right-handed, as revealed by neuropsychological

testing, and it is known that right-handedness is usually associated with left-hemispheric

dominance for language (see, for example, Knecht et al., 2000). The effect of left-

hemispheric TMS is therefore best explained by interference with cortical language

networks lateralized to the left hemisphere. For subjects with strong left-handedness, one

may expect similar effects to occur after TMS to the right hemisphere as well (Knecht et

al., 2002). Although no significant effect of right-hemispheric TMS was present in the

present population of strong right-handers, this does not exclude a possible contribution

of right-hemispheric functions to language processing in this population. For example,

17

fine-grained word-category-specific deficits can follow focal ischaemic lesions in the

right frontal lobe in right handed neurological patients (Neininger and Pulvermüller,

2001, 2002). Thus, while the present TMS results support an extended left-hemispheric

network contributing to language processing, they do not argue against a contribution of

right-hemispheric circuits to language processing.

The suggestion that semantic factors can determine the cortical loci at which magnetic

stimulation influences lexical processing, may lead one to ask whether other properties of

our word material may contribute to the differential facilitation of arm and leg words by

TMS to action-related cortical areas. The answer is that the likely alternative

explanations, based, for example, on features such as standardized lexical frequency,

familiarity, length or physical features, or imageability were carefully controlled in this

study and can therefore be ruled out as possible confounds, as discussed in Material and

Methods. Also, from a linguistic perspective, all words could be used as English verbs

with some of them having additional possible uses as nouns or adjectives. The fact that

the lexical categories of the arm and leg words were the same discourages an explanation

of the effect in terms of grammatical word categories. The effect appears to be due to

word meaning, more precisely to the type of action the words regularly refer to.

The question why facilitatory effects of TMS, rather than inhibitory ones, were

obtained in this study is difficult to answer. The leg words were processed 32 ms faster

when TMS pulses were applied to the left leg stimulation locus compared with the

responses to the same words in the control condition, and their processing was 35 ms

faster in comparison with arm-related words in the same TMS condition. We note that

this is not the first study revealing speeding of language or other cognitive processes as a

18

consequence of TMS (see, for example, Epstein, 1998; Sparing et al., 2001). For

example, as we have pointed out in the Introduction, stimulation of Wernicke's area was

found to facilitate naming (Mottaghy et al., 1999), an effect that depends on the choice of

stimulation parameters (Sparing et al., 2001). We suggest that, in the present study, the

low intensity, about 90% of the motor threshold, was important for obtaining facilitation,

and that the stimulus onset asynchrony between onset of word presentation and the TMS

pulse was relevant as well. In earlier neurophysiological studies, responses differentiating

between lexical items and pseudowords, as well as between lexical and semantic word

categories, have been reported to be present around 200 ms after the onset of visual word

presentation (for review, see Pulvermüller, 2002). Our choice of an SOA of 150 ms was

motivated by this observation. We hoped to provide cortical areas potentially relevant in

word processing with additional activity just before the activity wave caused by the word

stimulus reaching these critical areas. In this view, the TMS pulse applied to areas that

potentially play a role in the processing of word meaning has a similar effect as priming

by presentation of semantically related words. Semantic priming is known to have a

robust and immediate facilitatory effect on the processing of target words which has a

clear neurophysiological correlate (Kiefer, 2002). It is possible that similar facilitatory

effects can be caused by TMS. The results reported here suggest that this facilitatory

effect can be both locally specific within the cortex and restricted to a semantically

defined category of words, for example leg-related action words in the present case.

Closely following ethical guidelines, it was not possible in the present study to localize

an area where an EMG response in leg muscles could be elicited by TMS. The primary

motor cortex controlling leg movements is known to be mostly hidden in the

19

interhemispheric sulcus in man (Penfield and Rasmussen, 1950), and, in order to cause a

leg muscle contraction by TMS, high intensities are therefore necessary. The leg

stimulation loci were placed a few centimeters superior to the arm stimulation loci, which

had been determined using TMS-evoked EMG responses. The pre-motor cortex is to a

large extent localized on the outer surface of the cortex and is therefore easier to

influence using magnetic pulses (He et al., 1993; Buccino et al., 2001; Rizzolatti et al.,

2001). Thus, the stimulated area superior to the arm motor representation included part of

the leg representation in the pre-motor cortex. A TMS pulse can influence a cortical area

of several square centimeters (Ilmoniemi et al., 1997), and, therefore, a large area may

have been stimulated, including substantial parts of pre-motor and possibly prefontal

cortex. The stimulation of pre-motor sites may be relevant for obtaining facilitatory

effects.

An earlier study reported a deterioration of verb processing as a consequence of

prefrontal TMS (Shapiro et al., 2001). The question why these authors observed

inhibition while we saw facilitation may find an answer in aspects of the methods

applied: Shapiro and colleagues used rTMS (300 pulses at 1Hz stimulation rate), whereas

in the present study, single pulses were delivered. Stimulation intensity was 110% of the

motor threshold in Shapiro's study and about 90% in ours. Further investigation of the

factors determining the excitatory or inhibitory direction of the behavioral and

neurophysiological effects of TMS remain for future research. Regardless of the direction

the effect takes, the study by Shapiro and colleagues and ours converge on the finding

that word category specific processes can be induced by TMS, thus providing further

support that words of different kinds are processed by neuronal assemblies with distinct

20

cortical topographies (Pulvermüller, 1999). From a linguistic point of view, it is

important to note that both a difference in lexical category (nouns vs. verbs) and a

semantic difference (leg action words vs. arm action words) can crucially underlie the

difference in cortical representation and processing.

The differential modulation of arm- and leg-word processing by TMS to arm- and leg

motor areas can be explained on the basis of the concept of mirror neurons in the pre-

motor cortex, whose activation relates to both the performance of an action and the

perceptions related to the same action (Rizzolatti and Luppino, 2001; Rizzolatti et al.,

2002). The networks determining the mirror neuron behavior likely include long-distance

links bridging between sensory and pre-motor cortical areas. These networks may form

on the basis of associative learning, and similar networks may link the cortical

representation of a word form to that of the actions the word refers to (Pulvermüller,

2001). Cortical networks linking neurons controlling leg movements to word forms may

underlie the facilitation of leg words by TMS to the leg locus. The corresponding effect

after arm-locus stimulation may crucially depend on the connections between the

representations of arm movements and word forms of arm-related words. The present

research provides further support that specific information about word semantics,

reference to action, is tightly linked, at the cortical level, to the representation of word

forms.

21

5. Acknowledgement

We thank Chris Bailey, Dubravko Kicic, Tuomas Murdoch and Yury Shtyrov for help at

different stages of this work.

22

6. References

Bailey CJ, Karhu J, Ilmoniemi RJ (2001) Transcranial magnetic stimulation as a tool for

cognitive studies. Scand J Psychol 42:297-305.

Buccino G, Binkofski F, Fink GR, Fadiga L, Fogassi L, Gallese V, Seitz RJ, Zilles K,

Rizzolatti G, Freund HJ (2001) Action observation activates premotor and parietal

areas in a somatotopic manner: an fMRI study. Eur J Neurosci 13:400-404.

Epstein CM (1998) Transcranial magnetic stimulation: language function. Journal of Clin

Neurophysiol 15:325-332.

Epstein CM, Lah JJ, Meador K, Weissman JD, Gaitan LE, Dihenia B (1996) Optimum

stimulus parameters for lateralized suppression of speech with magnetic brain

stimulation. Neurology 47:1590-1593.

Epstein CM, Meador KJ, Loring DW, Wright RJ, Weissman JD, Sheppard S, Lah JJ,

Puhalovich F, Gaitan L, Davey KR (1999) Localization and characterization of

speech arrest during transcranial magnetic stimulation. Clin Neurophysiol

110:1073-1079.

Fadiga L, Craighero L, Buccino G, Rizzolatti G (2002) Speech listening specifically

modulates the excitability of tongue muscles: a TMS study. Eur J Neurosci

15:399-402.

He SQ, Dum RP, Strick PL (1993) Topographic organization of corticospinal projections

from the frontal lobe: motor areas on the lateral surface of the hemisphere. J

Neurosci 13:952-980.

Ilmoniemi RJ, Virtanen J, Ruohonen J, Karhu J, Aronen HJ, Naatanen R, Katila T (1997)

23

Neuronal responses to magnetic stimulation reveal cortical reactivity and

connectivity. Neuroreport 8:3537-3540.

Jasper H (1958) The 10-20 electrode system of the international federation.

Electroencephalogr Clin Neurophysiol 10:371-375.

Kiefer M (2002) The N400 is modulated by unconsciously perceived masked words:

further evidence for an automatic spreading activation account of N400 priming

effects. Cognit Brain Res 13:27-39.

Knecht S, Drager B, Deppe M, Bobe L, Lohmann H, Floel A, Ringelstein EB,

Henningsen H (2000) Handedness and hemispheric language dominance in

healthy humans. Brain 123 Pt 12:2512-2518.

Knecht S, Floel A, Drager B, Breitenstein C, Sommer J, Henningsen H, Ringelstein EB,

Pascual-Leone A (2002) Degree of language lateralization determines

susceptibility to unilateral brain lesions. Nature Neurosci 5:695-699.

Lagerlund TD, Sharbrough FW, Jack CR, Jr., Erickson BJ, Strelow DC, Cicora KM,

Busacker NE (1994) Determination of 10-20 system electrode locations using

magnetic resonance scanning with markers. Electroencephalogr Clin

Neurophysiol 86:7-14.

Maeda F, Keenan JP, Tormos JM, Topka H, Pascual-Leone A (2000) Interindividual

variability of the modulatory effects of repetitive transcranial magnetic

stimulation on cortical excitability. Exp Brain Res 133:425-430.

Michelucci R, Valzania F, Passarelli D, Santangelo M, Rizzi R, Buzzi AM, Tempestini

A, Tassinari CA (1994) Rapid-rate transcranial magnetic stimulation and

hemispheric language dominance. Neurology 44:1697-1700.

24

Mohr B, Pulvermüller F, Zaidel E (1994) Lexical decision after left, right and bilateral

presentation of content words, function words and non-words: evidence for

interhemispheric interaction. Neuropsychologia 32:105-124.

Mottaghy FM, Hungs M, Brugmann M, Sparing R, Boroojerdi B, Foltys H, Huber W,

Topper R (1999) Facilitation of picture naming after repetitive transcranial

magnetic stimulation. Neurology 53:1806-1812.

Neininger B, Pulvermüller F (2001) The right hemisphere's role in action word

processing: a double case study. Neurocase 7:303-317.

Neininger B, Pulvermüller F (2002) Word-category specific deficits after lesions in the

right hemisphere. Neuropsychologia (in press).

Nikouline V, Ruohonen J, Ilmoniemi RJ (1999) The role of the coil click in TMS

assessed with simultaneous EEG. Clin Neurophysiol 110:1325-1328.

Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh

Inventory. Neuropsychologia 9:97-113.

Pascual-Leone A, Gates JR, Dhuna A (1991) Induction of speech arrest and counting

errors with rapid-rate transcranial magnetic stimulation. Neurology 41:697-702.

Pascual-Leone A, Bartres-Faz D, Keenan JP (1999) Transcranial magnetic stimulation:

studying the brain-behaviour relationship by induction of 'virtual lesions'. Philos

Trans R Soc Lond B Biol Sci 354:1229-1238.

Penfield W, Rasmussen T (1950) The cerebral cortex of man. New York: Macmillan.

Pulvermüller F (1999) Words in the brain's language. Behav Brain Sci 22:253-336.

Pulvermüller F (2001) Brain reflections of words and their meaning. Trends Cognit Sci

5:517-524.

25

Pulvermüller F (2002) A brain perspective on language mechanisms: from discrete

neuronal ensembles to serial order. Prog Neurobiol 67:85-111.

Rijntjes M, Weiller C (2002) Recovery of motor and language abilities after stroke: the

contribution of functional imaging. Prog Neurobiol 66:109-122.

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

Rizzolatti G, Fogassi L, Gallese V (2001) Neurophysiological mechanisms underlying

the understanding and imitation of action. Nature Rev Neurosci 2:661-670.

Rizzolatti G, Fogassi L, Gallese V (2002) Motor and cognitive functions of the ventral

premotor cortex. Curr Opin Neurobiol 12:149-154.

Ruohonen J, Ilmoniemi RJ (2002) Physical principles for transcranial magnetic

stimulation. In: Handbook of transcranial magnetic stimulation (Pascual-Leone A,

Davey NJ, Rothwell J, Wassermann EM, Puri BK, eds), pp 18-29. London:

Arnold Publishers.

Shapiro KA, Pascual-Leone A, Mottaghy FM, Gangitano M, Caramazza A (2001)

Grammatical distinctions in the left frontal cortex. J Cognit Neurosci 13:713-720.

Sparing R, Mottaghy FM, Hungs M, Brugmann M, Foltys H, Huber W, Topper R (2001)

Repetitive transcranial magnetic stimulation effects on language function depend

on the stimulation parameters. J Clin Neurophysiol 18:326-330.

Stewart L, Walsh V, Frith U, Rothwell J (2001) Transcranial magnetic stimulation

produces speech arrest but not song arrest. Ann N Y Acad Sci 930:433-435.

Virtanen J, Ruohonen J, Naatanen R, Ilmoniemi RJ (1999) Instrumentation for the

measurement of electric brain responses to transcranial magnetic stimulation. Med Biol

ng Comput 37:322-326.

26