specialisation in broca area

8/10/2019 Specialisation in Broca area

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Specialisation in Broca's region for semantic, phonological, and

syntactic fluency?

Stefan Heim,a,b, Simon B. Eickhoff,a, c and Katrin Amuntsa,b,d

aResearch Centre Jlich, Institute of Neurosciences and Biophysics (INB-3), Jlich, GermanybBrain Imaging Center West (BICW), Jlich, GermanycC. & O. Vogt Institut fr Hirnforschung, Heinrich-Heine Universitt, Dsseldorf, GermanydDepartment of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany

Received 21 August 2007; revised 28 December 2007; accepted 8 January 2008

Available online 19 January 2008

The literature suggests that that semantic and phonological fluency tasks

selectively activate left Brodmann's area (BA) 45 and 44, respectively, in

Broca's speech region. We used functional MRI to test this hypothesis.

Subjects performed a semantic and a phonological fluency task. In

addition, a syntactic fluency task (e.g. Generate nouns with masculine

gender) was included. Resting blocks were included as a low-level

control condition. The exact localisation of the effects was tested with

cytoarchitectonic probability maps of BA 44 and BA 45. Participants

generated fewer words in the syntactic than in both the semantic and the

phonological condition, which did not differ from each other. Compared

to rest, all language tasks activated the well-known language network in

the left hemisphere including both left BA 44 and BA 45. In the direct

contrasts between the different verbal fluency tasks, phonological

fluency activated BA 44 more strongly than semantic or syntactic

fluency. However, semantic fluency did not elicit higher activation thanthe phonological fluency tasks in any part of Broca's region. No

differences were observed between syntactic and semantic fluency. Thus,

the activation in BA 45 observed during verbal fluency tasks seems to be

not restricted to semantic processing as suggested by the literature. In

contrast, phonological verbal fluency additionally involved the left BA

44. In conclusion, different parts of Broca's region support task-specific

and more general processes in verbal fluency.

2008 Elsevier Inc. All rights reserved.

Introduction

In verbal fluency tasks participants are required to produce

words according to a given criterion. Typical examples for verbal

fluency tasks are the generation of words of a particular semantic

category (e.g. animals;semantic fluency) or with a given letter or

sound (e.g. words starting with F; phonological fluency). The

word generation may either be overt or covert. It can follow the

subject's own speed (i.e. self-paced) or be externally paced by the

experimenter (cf.Basho et al., 2007).

Verbal fluency tasks have since long (e.g. Burt, 1917; Lotsof,

1953; Rogers, 1953) been standard paradigms in psychology,

psychiatry, and neurology (e.g. Frith et al., 1995; Gaillard et al.,

2000; Monsch et al., 1992) for testing the cognitive abilities of

patients or for identifying language-related brain regions before

neurosurgery. The advent of neuroimaging techniques such as

functional magnetic resonance imaging (fMRI) revealed that

verbal fluency recruits the left inferior frontal gyrus (IFG)

including Broca's speech region. A recent meta-analysis (Costa-

freda et al., 2006) demonstrated that different types of verbal

fluency recruit different aspects of the left IFG: Whereas semanticfluency tasks tended to activate a more ventral-anterior portion of

the IFG (roughly corresponding to Brodmann's area [BA] 45),

phonological fluency appeared to involve a more dorsal-posterior

aspect (approximately BA 44). This finding was seen in

accordance with recent neurocognitive models of language

processing describing a functional parcellation for semantic,

syntactic, and phonological processing in the IFG (e.g. Book-

heimer, 2002; Friederici, 2002; Hagoort, 2005) and with patient

data (Szatkowska et al., 2000).

Although the results by Costafreda et al. (2006) are appealing,

some issues remain to be addressed. First, as the authors

acknowledged, none of the included studies directly compared

semantic and phonological fluency in the same subjects. This is

critical because only such direct comparison of two tasks allows a

precise assessment of activation differences. Second, the meta-

analysis was performed on the locations of the peak activations,

which do not reflect the extent of the activation clusters. This

implies that the actual activations in the single studies may have

been more blurred than suggested by the location of the local

maxima. Third, the assignment of the peak coordinates to BA 44 or

BA 45 was only based on macroanatomical criteria, i.e. the sulcal

pattern in the IFG. However, asAmunts et al. (1999)demonstrated,

borders of cytoarchitectonically defined brain areas such as BA 44

or BA 45 do not necessarily coincide with the sulcal landmarks.

www.elsevier.com/locate/ynimgNeuroImage 40 (2008) 1362 1368

Corresponding author. Research Centre Jlich, Institute of Neuros-

ciences and Biophysics, 52425 Jlich, Germany. Fax: +49 2461 61 2820.

E-mail address:[email protected](S. Heim).

Available online on ScienceDirect (www.sciencedirect.com).

1053-8119/$ - see front matter 2008 Elsevier Inc. All rights reserved.

doi:10.1016/j.neuroimage.2008.01.009
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Thus, the assignment of the coordinates to BA 44 and BA 45

in the study by Costafreda et al. (2006) remains imprecise with

respect to the underlying cortical areas.

Therefore, we tested the hypothesis that semantic and

phonological fluency recruit left BA 45 or BA 44, respectively,

in a new functional imaging study that compared different types of

verbal fluency in the same subjects. The localisation of the effectswas assessed with cytoarchitectonic probability maps of Broca's

region (Amunts et al., 1999, 2004).

Materials and methods

Participants

28 healthy right-handed participants (mean age 29.4 years; 14

females) participated in the experiment. They were native German

speakers and had normal or corrected-to-normal vision. Participants

had no history of neurological or psychiatric disorders. Informed

consent was obtained from all participants. The experimental

standards were approved by the local ethics committee of the

University of Aachen.

Tasks

A total of four overt word generation tasks were applied in

German: semantic, syntactic, phonological, and free (no explicit

criterion). Each generation task was performed in six blocks (see

below). In the semantic fluency task subjects had to overtly

generate examples for the following six categories: birds,

mammals, food, weapons, tools, and toys. In the phonological

fluency task the participants were required to generate nouns

starting with the following phonemes: /b/, /f/, /k/, /m/, /sh/, and /t/.

In the syntactic fluency task, nouns with masculine, feminine, or

neuter gender had to be produced. The syntactic fluency task was

included since, according to the model of language production by

Levelt et al. (1999; seeFig. 1), it taps a level in the mental lexicon

(the lemma level) which is not targeted by the other two fluency

tasks. According to recent neurocognitive models of language

(Friederici, 2002; Hagoort, 2005) syntactic fluency should also

activate BA 44 and/or BA 45. A free generation task in which the

participants produced any nouns without a predefined criterion was

administered as a high-level baseline task controlling for the

retrieval and articulation of words. In addition, resting blocks were

included as a low-level baseline.

In the present paper the term verbal fluency task(s) will be

used when referring to the semantic, syntactic, or phonological

fluency task as opposed to the free word generation baseline. In

contrast, word generation (tasks)

includes the verbal fluencytasks and the free word generation baseline, and is used to contrast

these tasks requiring overt speech to the resting baseline.

Stimulus Presentation

Visual stimuli were presented as written strings in Helvetica

font at 48 pts via goggles (VisuaStim, Resonance Technology,

CA, USA). Stimulus presentation was controlled by a computer

placed in the control room using Presentation software (Neurobe-

havioral Systems, Albany, CA, USA).

The study employed a block design. There were six blocks for

each condition and 24 resting blocks separating the task blocks.

Before each task block a written instruction was presented for

6 seconds. The blocks started immediately after that instruction and

lasted for 20 seconds. The condition blocks were presented in a

pseudo-randomised order, with different randomisations for eachparticipant. The total duration of the experiment was 19 minutes.

Each block included ten repetitions of experimental trials

(generation of a single word). Each trial lasted 2 seconds. The

fMRI data wereacquiredin the first 1.04 seconds of eachtrial usinga

bunched-early sequence (see below). After this time, a fixation cross

appeared for the remaining 0.96 seconds of silence, indicating the

subject that he or she could now utter the next word during a silent

period (see Fig. 2and the section Data Acquisition and Analysis;

cf.Heim et al., 2002; de Zubicaray et al., 2001, 2002).

This procedure combines a number of advantages. First, it

prevents motion-induced susceptibility artefacts, since subjects

only speak when no fMRI data are recorded. Second, the scanner

noise is not superimposed on the verbal response. Consequently,

the subject's utterances can be better evaluated during or after the

experiment to assess the number of produced items. Finally, cueing

the overt speaking implies paced word generation, which has been

shown to reduce head motion during speaking as compared to

unpaced generation (Basho et al., 2007).

Speech recordings

The participants' speech production was recorded using the

microphone of the goggle system. The cable from the microphone

to the patient intercom in the MR control room was plugged there

into a splitter, from which one cable led to the intercom and one to

the line-in port of an external sound card attached to a Toshiba

Fig. 1. The serial model of language production by Levelt et al. (1999).

Semantics (concept), syntax (lemma), and phonology of a word are retrieved

during different stages of the production process. The fluency tasks tapping

the different stages are indicated.

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notebook used for digital recording. These recordings were used

for qualitative and quantitative analyses of the participants' overt

responses in each condition, yielding information about what they

said and how many items were generated.

Data acquisition and analysis

Functional and anatomical data

The fMRI experiment was carried out on a 3T Siemens Trio

scanner. A standard birdcage head coil was used with foam paddings

reducing head motion. The functional data were recorded from 17

sagittal slices in the left hemisphere using a gradient-echo EPI

sequence with echo time (TE)=30 ms, flip angle=90 degrees, and

repetition time (TR)=2 s. The sagittal orientation of the slices was

chosen in order to correct head motion in-plane, which is highest in the

yzplane. Acquisition of the slices within the TR was arranged so that

all slices were acquired in the first 1040 ms, followed by a 960-ms

period of no acquisition to complete the TR during which the subjects

spoke. The field of view (FOV) was 200 mm, with an in-plane

resolution of 3.1 mm 3.1 mm. The slice thickness was 3 mm with an

inter-slice gap of 1 mm. In addition, anatomical T1-weighted MP-

RAGE images (resolution 1 mm1 mm1 mm, FOV=256 mm,

TR= 2250 ms, TE= 3.03 ms, flip angle= 9 degrees) werealsoobtained.

The data processing was performed using MATLAB 6.5 (The

Mathworks Inc., Natick, USA), and SPM5 (Wellcome Department

of Cognitive Neurology, UK). Two dummy scans before the

beginning of the experiment were discarded to allow for magneticsaturation. Data pre-processing included the standard procedures of

realignment, normalisation to the MNI single subject template, and

spatial smoothing (FWHM=8 mm).

Head motion parameters were as follows: The mean translations

were0.08 mm (x), 0.2 mm (y), and 0.5 mm (z), with corresponding

rotations of 0.04degrees, 0.03degrees, and 0.03degrees, respectively.

For the statistical analysis at the single participant level, the block

functions for each word generation condition were convolved with a

canonical haemodynamic response function (HRF). For each

participant, the contrasts of each task vs. rest were calculated. For

the group analysis, the individual contrast images were entered into a

repeated-measures ANOVA as a second level random effectsanalysis.

From this ANOVA the following low-level baseline contrasts were

calculated: SemanticNRest, SyntacticNRest, and PhonologicalNRest.

Moreover, a conjunction analysis (Price and Friston 1997) was per-

formed to assess brain regions significantly activated in all three

fluency conditions. Finally, the relative differences between the three

fluency tasks were tested in pair-wise comparisons.

Anatomical localisation of the fMRI dataFor the anatomical localisation we used cytoarchitectonic

probability maps of BA 44 and BA 45 in Broca's region (Amunts

et al., 1999, 2004). These maps are based on an observer-independent

analysis of the cytoarchitecture in a sample of ten post-mortem brains

(Schleicher et al., 1999; Zilles et al., 2002). They provide information

about the location and variability of cortical regions in standard MNI

space. For the assignment of coordinates to cytoarchitectonically

defined regions, we used the SPM Anatomy Toolbox (Eickhoff et al.,

2005; available with all published cytoarchitectonic maps from www.

fz-juelich.de/ime/spm_anatomy_toolbox ).

Since the present study was designed to test a hypothesis about

the differential involvement of the left BA 44 and BA 45 in different

verbal fluency tasks, the analysis wasconfined to these two areas in a

region of interest (ROI) analysis. The combined maximumprobability maps of BA 44 and BA 45 were used as the search

volume for small volume corrections (SVC) when differential task

effects in Broca's region were examined (Eickhoff et al., 2006).

Results

Behavioural data

The subjects produced on average (standard error of mean)

46.8 (1.2) words in the semantic fluency task, 40.9 (1.7) words

Fig. 2. Speaking during scanning: A bunched-early EPI sequence was used for

the acquisition of the fMRI data. All slices were recorded in the first 1.04

seconds of theTR, resulting in a silent period of 0.96 seconds in thesecond half

of the TR. During this silent period, the participants generated the words. The

speechsignal is clearly discernable, since it is not obscuredby thescanner noise.

Fig. 3. Top:Activation in the left cytoarchitectonic BA 44 andBA 45 in semantic

fluency (red), syntacticfluency (yellow), andphonologicalfluency(cyan).Bottom:

Conjunction analysis of the three fluency conditions and activation strength (beta

values) at the local maxima in BA 44 and BA 45. Abbreviations: L, left; R, right;

SEM, semantic fluency; SYN, syntactic fluency; PHO, phonological fluency.

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in the syntactic fluency task, 45.3 ( 1.3) words in the phonological

fluency task, and 56.5 (0.7) words in the free generation task.

The one-factorial repeated-measures ANOVA of the number of

generated items yielded a main effect for task (F1,29=97.3;pb .001).

The post-hoc contrasts revealed that the subjects produced signifi-

cantly (allpb .001) more words in the free generation task than in any

of the fluency tasks (semantic vs. free: t29=

10.8; syntactic vs. free:t29=12.2; phonological vs. free: t29=9.2). Among the fluency

tasks, less words were produced in the syntactic condition than in the

semantic (t29=5.5; pb .001) or the phonological (t29=3.9; p =.001)

condition. No difference was present between the semantic and the

phonological condition (t29=1.4;p =.174).

In the phonological task subjects produced on average 8.1

words with /b/, 8.0 words with /t/, 7.6 words with /k/, 7.2 words

with /m/ and with /sh/, and 7.1 words with /f/. This ranking seems

to differ from the ranking according to the frequency of occurrence

of the corresponding letters in German, which is 1.89% for B,

6.15% for T, 1.21% for K, 2.53% for M, 7.27% for S/SH, and

1.66% for F (URL: http://de.wikipedia.org/wiki/Buchstabenh%

C3%A4ufigkeit#_note-1).

The qualitative analysis of the participants' verbal responsesrevealed that only few errors were made, with highest error rates in

syntactic fluency (semantic: 1.1%; syntactic: 3.2%; phonological:

0.2%). However, it appeared that in the free generation condition the

participants engaged various strategies that were either phonological

(a series of words with the same initial phoneme), semantic (items

from related categories), or scenic/imagery (participants imagined e.g.

a room and named theobjectsin this room).Suchstrategies resulted in

a supposedly inconsistent free generation baseline which could

obscure task-related activation in the other three generation conditions

if these were compared to it. We therefore refrained from using the

free generation condition as a high-level baseline condition. Instead,

as planned, we compared the task-related activations against the

resting baseline and pair-wise with each other.

fMRI data

The brain activation effects in Broca's region for contrasting each

single verbal fluency task against the resting baseline are displayed in

Fig. 3(top row) and listed in Table 1(allpcorr

b.05 are FWE-corrected

for the search volume of BA 44 and BA 45, kN10 voxels). Semantic

fluency elicited activation in the left cytoarchitectonic BA 44

(maximum cytoarchitectonic probability: 60%) and BA 45 (maximum

cytoarchitectonic probability: 40%). Syntactic fluency also activated

both BA 44 (maximum cytoarchitectonic probability: 40%) and BA

45 (maximum cytoarchitectonic probability: 40%). Finally, phonolo-

gical fluency also activated BA 44 (maximum cytoarchitectonic

probability: 50%) and BA 45 (maximum cytoarchitectonic prob-

ability: 40%). A conjunction analysis of all three fluencies (Fig. 3,

bottom row) revealed common significant activation in the left BA 44(maximum cytoarchitectonic probability: 60%) and BA 45 (maximum

cytoarchitectonic probability: 40%).

Table 1

MNI coordinates and Tvalue (Tmax) at the local activation maxima in the

contrasts of each fluency task against the resting baseline (pcorr

b.05 are

family-wise error corrected for the search volume of BA 44 and BA 45)

Coordinates

Contrast BAcyto x y z T max

SemanticNRest 44 52 2 23 8.30

45 44 26 25 5.55

SyntacticNRest 44 52 2 23 8.00

45 44 26 25 6.39

Phonological NRest 44 52 6 23 8.76

45 44 28 23 5.61

Conjunction analysis 44 52 2 23 8.00

45 44 28 23 5.49

The cytoarchitectonic Brodmann's area (BAcyto) at the local maximum (see

Amunts et al., 2004) is given.

Table 2

Localisation of the peak activations in the differential contrasts of the verbal

fluency tasks (atpcorrb.05 SVC for Broca's region, kN10 voxels)

Coordinates

Contrast BAcyto x y z T max

SemanticNSyntactic n.s.

SyntacticNSemantic n.s.SemanticNPhonological n.s.

Phonological NSemantic 44 50 10 21 6.93

SyntacticNPhonological n.s.

Phonological NSyntactic 44 50 8 23 5.16

For details see the legend ofTable 1. Further abbreviation: n.s., not significant.

Fig. 4. Top: Surface renderings of brain activation (atPb.05 whole-brain

FWE-corrected) of semantic (SEM) and phonological (PHO) fluency

compared to the resting baseline (REST) reveal comparable patterns.

Bottom: Differential fMRI effects (atPb.05 whole-brain FWE-corrected) of

semanticNphonological fluency and phonologicalNsemantic fluency.

http://de.wikipedia.org/wiki/Buchstabenh%C3%A4ufigkeit#_note-1http://de.wikipedia.org/wiki/Buchstabenh%C3%A4ufigkeit#_note-1http://de.wikipedia.org/wiki/Buchstabenh%C3%A4ufigkeit#_note-1http://de.wikipedia.org/wiki/Buchstabenh%C3%A4ufigkeit#_note-1


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The differential contrasts between the three verbal fluency tasks

are reported in Table 2 (all pcorr

b.05 are FWE-corrected for the

search volume of BA 44 and BA 45, kN10 voxels). The activation

in the phonological vs. syntactic fluency and in the semantic vs.

syntactic fluency did not differ significantly. Phonological fluency

yielded higher activation than semantic fluency in BA 44 (maximum

cytoarchitectonic probability: 50%). The reverse contrast was notsignificant in Broca's region. Phonological fluency also yielded

higher activation than syntactic fluency in BA 44 (maximum

cytoarchitectonic probability: 50%). Again, the reverse contrast did

not reach significance within Broca's region.

Outside Broca's region semantic fluency showed higher activation

than phonological fluency in the left middle frontal gyrus (60,10,

23;t=7.29) and the left fusiform gyrus (28, 38, 19;t=5.71).

The reversed contrast yielded higher activation for phonological than

for semantic fluency in the left inferior parietal lobule (40,40, 47;

t=6.55) which was due to deactivation in the semantic rather than

activation in the phonological condition. These effects (all Pcorr

b.05

whole-brain are FWE-corrected) are displayed in Fig. 4 (bottom).

Discussion

In the present study we tested the hypothesis that the left BA 44

supports phonological fluency whereas the left BA 45 is engaged

in semantic fluency. To this end we compared semantic, phonolo-

gical, and syntactic verbal fluency in an fMRI study and super-

imposed the results on cytoarchitectonic maps of BA 44 and BA 45.

The data are only partly in line with this hypothesis. Compared to a

resting baseline, semantic fluency indeed activated BA 45. More-

over, phonological fluency yielded activation in BA 44 which was

higher than activation in BA 44 in any other task. So far, these data

corroborate the meta-analysis byCostafreda et al. (2006) and our

previous results that semantic fluency involves cytoarchitectonic

BA 45 (Amunts et al., 2004).

The observed pattern of activations, however, was more complex

than previously assumed, since activation in BA 45 was also present

during phonological and syntactic fluency. Likewise, the activation

in BA 44 was also observed for semantic and syntactic fluency.

These findings are not in line with the hypothesis that BA 44 and BA

45 are specialised for phonological vs. semantic fluency, respectively.

Therefore, alternative interpretations need to be considered.

The comparable effects in BA 45 in all three conditions may

reflect an unspecific aspect of verbal fluency shared by all three

fluency tasks rather than condition-specific demands. This idea is in

accordance with the findings byRogers (1953)who observed in a

factor analysis of behavioural data from different fluency tasks one

factor for general verbal ability and another for oral verbal

ability. Interestingly, and supporting the observation of comparableengagement of inferior frontal areas in the present study, no evidence

for separate factors for semantic, syntactic, or phonological fluency

was obtained in the Rogers (1953) study. Therefore, it would be

plausible to attribute the unspecific activation in BA 45 in all

fluency tasks to a general selection mechanism possibly related to

Rogers' (1953) oral verbal ability. Further support for our position

comes from a study byGold and Buckner (2002)who also observed

comparable inferior frontal activation during the controlled proces-

sing of semantic and phonological information. Moreover, in

addition to the shared inferior frontal activation in both tasks, the

authors found a functional dissociation of semantic and phonolo-

gical processing in inferior parietal and temporal regions. In

particular, the left inferior parietal lobule was activated more

strongly for phonological than for semantic processing. This finding

could be replicated when directly contrasting phonological vs.

semantic fluency in the present study.

Given the data from the Gold and Buckner (2002) study the

activation in the present study in BA 44 and BA 45 in all fluency

tasks maybe related to the controlledretrievalof lexical information.

This argument is also in line with other studies showing that the leftIFG supports lexical selection processes (e.g. Badre et al., 2005; Kan

and Thompson-Schill, 2004; Snyder et al., 2007). When additionally

considering the behavioural results in the present study one may

even be more specific about thenature of the process reflected by the

activation in BA 44 and BA 45. If this activation was related to

lexical selection it should vary as a function of taskdifficulty, i.e., the

number of words produced in each condition. This is exactly what

we observed. There was no difference in the activation in semantic

and phonological fluency, which proved equally difficult when

considering the number of produced words in both conditions. In

contrast, the activation was significantly higher in the syntactic

fluency task which, according to the number of produced items and

also to the error rates, was the most difficult one. To conclude, the

activation data are compatible with the view that Broca's regionsupports a rather unspecific selection mechanism that is shared by

semantic, phonological, and syntactic verbal fluency and that is

sensitive only to the difficulty of the selection.

Alternatively, one might suppose that the activation effects in

Broca's region do not reflect some unspecific selection mechanism,

but distinct processes which are specific for semantic fluency,

syntactic fluency, or phonological fluency, respectively.

The present study cannot provide ultimate evidence against this

view. However, the scenario is not very convincing given that the local

maxima in particular in BA 45 were at almost identical coordinates.

But even if one assumed some condition-specific function in BA 45 it

is nonetheless striking that semantic and phonological fluency showed

no differential effects, in particular given the large sample size in the

present study. To conclude, the observed effects are best understood as

reflecting lexical selection for verbal fluency in BA 45 which is not

specific for the actual type of fluency.

Another cognitive process that could be reflected by the activation

of BA 45 common to all three fluency conditions is working memory.

Verbal working memory has been reported to activate the dorsal

aspect of the posterior IFG (dorsal aspect of pars opercularis:

Zurowski et al., 2002; dorsal aspect of pars triangularis: see the meta-

analysis by Vigneau et al.,2006). Thus,one couldassume that a verbal

working memory component which is shared by the three fluency

tasks is reflected in the activation in BA 45. In particular, it has to be

considered that this study used a paced fluency paradigm in which the

participants had to utter one word every 2 seconds. The participants

might have internally generated words at a faster rate (e.g. a rate of 1word every 1.5 seconds was used by Ischebeck et al., in press) and

rehearsed this item until the cue to speak aloud. However, the

combination of the imaging datawith the behaviouraldata renders this

argumentation rather unlikely, for the following reason. If the

activation in BA 45 reflected verbal working memory the activation

should increase with the increasing number of generated words, since

a higher number of generated words implies a higher number of trials

during which these words must be kept in working memory, resulting

in a higher working memory load. However, no such pattern was

observed. Activation in BA 45 was equally high in all conditions

despite the fact that significantly different numbers of words were

produced. Therefore, although we cannot entirely rule out a

contribution of working memory processes, the idea that the

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activation in BA 45 in all three fluency tasks was primarily related to

verbal working memory is unlikely given the behavioural results.

The activation effects in BA 44 were distinct from those in BA 45.

Although all three fluency tasks significantly activated BA 44, they did

not do so to the same extent. Rather, BA 44 yielded higher activation

for phonological than for semantic (or syntactic) fluency. On the one

hand, such pattern of effects provides an argument against the initialhypothesis of a selective involvement of BA 44 in phonological

fluency, since semantic and syntactic fluency also recruited BA 44.

However, whereas the balance of all three types of activation was

similar to each other in BA 45, phonological fluency was emphasized

in BA 44, thus indicating its relevance in this particular area. An

explanation might incorporate the view that BA 44 supports two

different types of processes: (i) specific for phonological fluency and

(ii) relevant for all tested types of fluency. Two candidate processes are

controlled vs. automatic phonological processing. The relevance of

BA 44 for controlled phonological processing (e.g. during phonolo-

gical decisions) has been demonstrated earlier (e.g. Burton et al., 2000;

Dmonet et al. 1992; Heim et al. 2003; Zatorre et al. 1992). Such

controlled processing is also required during phonological fluency

where phonological cues need to be used as criteria for word retrieval.In addition to its role in controlled processing, it has also been shown

that BA 44 is involved in object naming during the automatic retrieval

of phonological information prior to articulation (for a review of object

naming studies cf. e.g. Price et al. 2005). Since controlled and

automatic phonological processing may occur independently from and

on top of each other in BA 44 (Noesselt et al. 2003), the effects in BA

44 observed in the present study could be explained as the summation

of activation from controlled and automatic phonological processing.

Such summation only occurs during phonologically cued word

generation but not during syntactic and semantic word generation,

where other thanphonological cues are relevant. For the purpose of the

present study one may conclude that BA 44 is relevant for all tested

types of verbal fluency and, in particular, for phonological fluency.

The present study used cytoarchitectonically defined volumes of

interest in order to test the hypothesis of functional specialisation

within Broca's region for semantic and phonological verbal fluency.

Beside the obvious advantages of this method with respect to

(1) observer-independence and availability of quantitative data (e.g.

Amunts et al., 2004) and (2) the use of anatomically-informed

regions of interest rather than spheres or boxes (Eickhoff et al.,

2006), thisapproachmight also have some drawbacks forthe present

study. So far only maps of BA 44 and BA 45 are available. In

contrast, BA 47 which is supposed to be located in the pars orbitalis

of the IFG, i.e. its most rostro-ventral part, has not yet been mapped.

Thus, when using the maps of BA 44 and BA 45 for the present

analysis we might systematically have ignored more anterior

activation in the IFG. This would be of importance in the case ofthe less strict anatomical hypothesis (e.g. Poldrack et al., 1999;

Vigneau et al., 2006) that phonological fluency involves the more

posterior part of the IFG (i.e. BA 44/45) whereas semantic fluency

recruits the more anterior portion (i.e. BA 45/47). However, the

whole-brain analyses of the semantic and the phonological fluency

tasks reveal that the anterior aspect of the left IFG was neither

activated in the tasks per se nor in the direct comparison of the two

tasks (Fig. 4 and Tables 2 and 3). Consequently, one may exclude the

possibility that the cytoarchitecture-based approach used in the

present study biased or obscured relevant data.

Finally, it should be noted that, even though the subjects produced

overt speech, the average head motion parameters were very small

and even below the values reported in earlier overt production

experiments (e.g. Gracco et al., 2005; Heim et al., 2006a). This

finding again demonstrates that overt language production is a valid

and useful paradigm for fMRI studies.

Conclusion

The present study tested whether the left cytoarchitectonic BA

44 and BA 45 specifically support phonological and semantic

fluency, respectively. However, both regions were involved in all

tested types of verbal fluency. Thus, the present study challenges

the contemporary view of a clear-cut functional parcellation of

Broca's region during verbal fluency. It seems that basically the

general demands on the selection of entries from the mental

lexicon rather than the particular linguistic domain (semantic or

phonological) are reflected by the amplitude of the fMRI signal in

verbal fluency tasks. Future studies may build upon the findings

from the present and earlier studies (e.g. Thompson-Schill et al.,

1997) and parametrically vary the selection demands in phonolo-

gical and semantic fluency.

Acknowledgments

This Human Brain Project/Neuroinformatics research is funded

by the National Institut e of Biomedical Imaging and Bioengine er-

ing, the National Institute of Neurological Disorders and Stroke,

and the National Institute of Mental Health (KA). Further support

by Helmholtz-Gemeinschaft (VH-N6-012 to KA) and the Brain

Imaging Center West (BMBF 01GO0204) is gratefully acknowl-

edged. We thank N. Jon Shah for the support of the NMR group at

the INB-3 during fMRI data acquisition, in particular Barbara

Elghahwagi for her assistance with fMRI data recording. More-

Table 3

Activations in the semantic and phonological fluency tasks in the left

hemisphere (Pcorrb.05 whole-brain are FWE-corrected)

Region x y z T max

SemanticNRest

Postcentral gyrus 46 10 41 13.12

Cerebellum

14

58

17 11.43Precentral gyrus 52 4 25 10.14

Caudate nuclues 16 10 21 8.62

Insula 34 16 5 7.89

Temporal pole 48 6 13 6.53

Inferior frontal gyrus 46 8 7 6.40

Fusiform gyrus 30 2 43 6.26

Middle temporal gyrus 58 30 5 5.61


Superior temporal gyrus 60 24 5 5.40

PhonologicalNRest

Postcentral gyrus 48 10 41 12.20

Cerebellum 16 58 19 10.27

Precentral gyrus 50 0 45 9.46

Caudate nuclues

14 0 17 8.53Insula lobe 34 16 5 7.93


Temporal pole 48 6 13 5.89


Putamen 18 6 9 5.43

Pallidum 50 6 5 5.34

Fusiform gyrus 30 2 43 5.27



7/7

over, we appreciate the support of the Cognitive Neurology group

at the INB-3 relating to the peripheral stimulation devices. Finally,

we wish to thank Helen Schreiber for her assistance with the

analysis of the behavioural data.

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