Functional Anatomy of Dominance for Speech Comprehension in Left Handers vs Right Handers

Functional Anatomy of Dominance for Speech Comprehensionin Left Handers vs Right Handers1

N. Tzourio, F. Crivello, E. Mellet, B. Nkanga-Ngila, and B. Mazoyer2

Groupe d’Imagerie Neurofonctionnelle, UPRES EA 2127 Universite de Caen and CEA LRC 13, 14074 Caen Cedex, France

Received December 11, 1997

In order to study the functional anatomy of hemi-spheric dominance for language comprehension wecompared the patterns of activations and deactiva-tions with PET and H2

15O during a story-listening taskin two groups of normal volunteers selected on thebasis of their handedness. The reference task was asilent rest. The results showed asymmetrical temporalactivations favoring the left hemisphere in right hand-ers (RH) together with Broca’s area and medial frontalactivations. A rightward lateralization of deactiva-tions located in the parietal and inferior temporalgyrus was also observed. In left handers (LH) thetemporal activations were more symmetrical as werethe parietal and inferior frontal deactivations. Broca’sarea and medial frontal gyrus activations were pres-ent in LH. The direct comparison of RH and LHactivations revealed larger activations in the left supe-rior temporal, in particular in the left planum tempo-rale and temporal pole of RH, while LH activated anadditional right middle temporal region. Individualanalysis of LH differences images superimposed onindividual MRI planes demonstrated an importantvariability of functional dominance, with two LH left-ward lateralized, two symmetrical, and one showing arightward lateralization of temporal activations. Therewas no relationship between functional dominanceand handedness scores. These results are in accor-dance with data from aphasiology that suggest agreater participation of the right hemisphere in lan-guage processing in LH. In addition, the presence ofbilateral deactivations of the dorsal route could sup-port the assumption that LH ambilaterality concerns,in addition to language, other cognitive functions suchas visuospatial processing. r 1998 Academic Press

Key Words: PET; language; temporal cortex; domi-nance; handedness.

INTRODUCTION

Cerebral dominance is a component of cerebral orga-nization that concerns major brain functions such aslanguage, movement, attention, and spatial processing.But since the discovery by Broca that language func-tions are lateralized to the left hemisphere in righthanders (RH), its origin, epigenesis, and consequencesfor brain organization are still under debate (Hiscockand Kinsbourne, 1995). Following his discovery thatlanguage functions were leftward lateralized in RH,Broca made the assumption that a mirror organizationshould be present in left handers (LH). However,aphasiology abandoned this concept which turned intothe study of language area variability and its relationto handedness and gender. Indeed, while the relation-ship between handedness and hemispheric dominancefor language appears to be quite strong in RH, itappears to be much harder to draw any conclusion inLH or ambidextrous subjects.

Results of the presurgical assessment of hemisphericlanguage dominance in patients suffering from intrac-table epilepsy, with the amobarbital test or Wada test(Wada and Rasmussen, 1960), have shown that 92 to99% of dextral individuals are left-hemisphere domi-nant for language (for review see Loring et al., 1990),while the pattern in nondextral individuals includesleftward, but also bilateral or even rightward, domi-nance for language in 15% of LH without any earlybrain injury, rising to 19% when subjects with earlybrain injury are included (Rasmussen and Milner,1977). As a matter of fact, early left-hemisphere lesionsappearing before the age of 1 or 3 can produce a shift inboth manual preference and cerebral dominance(Strauss and Wada, 1983; Vargha-Khadem et al., 1985).The incidence of such a phenomenon was thought to beeven underestimated and a review of Wada tests per-formed in 237 epileptic patients showed that takinginto account early brain injuries results in an absenceof correlation between handedness and hemisphericdominance for language (Woods et al., 1988), althoughthis conclusion should be taken with caution given thevery small sample of nonhemiparetic LH in the study.

1 This work was presented in part at the Third InternationalConference on Functional Mapping of the Human Brain, Copenha-gen, May 23–19, 1997.

2 To whom correspondence and reprint requests should be ad-dressed at GIP Cyceron, Boulevard Becquerel, BP 5229, 14074 CaenCedex, France. Fax: 33 2 31 47 02 22. E-mail: [email protected].

NEUROIMAGE 8, 1–16 (1998)ARTICLE NO. NI980343

1 1053-8119/98 $25.00Copyright r 1998 by Academic Press

All rights of reproduction in any form reserved.

The same conclusions were drawn from aphasiology.First studies showed that 60% of right handers withlesion in the left hemisphere developed aphasia, whileonly 32% of nondextral with lesion in the same hemi-sphere presented a language impairment (Benson,1962). Further studies by Hecaen on the comparison ofaphasia in right and left handers demonstrated that,although left-hemisphere lesions had the same effectson language functions in LH, albeit with more frequenttroubles in comprehension in RH, lesions of the righthemisphere resulted in troubles of oral and writtenlanguage in LH only (Gloning et al., 1969; Gloning,1977; Hecaen and Sauguet, 1971). Moreover, Hecaenshowed that LH with left posterior lesions had lessfrequent comprehension deficits but showed deficitsusually encountered in right hemisphere lesions in RHsuch as spatial disorientation (Hecaen and Ajuria-guerra, 1963). He concluded that LH present a greaterambilaterality for language and other lateralized func-tions, in particular when presenting familial sinistral-ity (Hecaen et al., 1981). The concept of a more frequentimplication of the right hemisphere in language process-ing in LH was challenged by Kimura, who, in a series of520 patients, confirmed that aphasia was less severe inLH but did not find more frequent aphasia in LH withleft or right lesions. He claimed that the right hemi-sphere had a negligible role in speech function in LHwithout early left hemisphere damage (Kimura, 1983).Presurgical mapping conducted with electrocorticalstimulations started from this point, namely the ab-sence of right-hemisphere lateralization of languageexcept after early left-hemisphere brain injury, andfocused on the investigations in the left hemisphere.These studies demonstrated that there was a great dealof language variability within the left hemisphere ofadults with left lateralization of language (Ojemann,1991).

From these clinical data it seems very difficult toextrapolate what would be the functional lateralizationfor language in normal subjects, as already pointed outby others (Woods et al., 1988). Moreover, little is knownabout the regions supplying hemispheric dominance forlanguage within the hemispheres, since the methodsused until today were of very low resolution: the Wadatest questions the whole hemisphere, while aphasiastudies frequently lack anatomical analysis and, whenthe latter is available, are limited by the usually largesize of the lesions. As for cortical mapping, it allows oneto document only the exposed cortex of the alteredhemisphere.

With this in mind, functional imaging appears as akey tool for such investigations. The functional anatomyof language has been extensively studied over the past10 years in RH (for review see Cabeza and Nyberg,1997; Frackowiak, 1994), but very few studies havebeen devoted to the question of the cerebral dominance

for language. Three functional imaging studies con-ducted in epileptic patients were designed to comparetheir results for functional dominance assessment withthose of the Wada test during either verb generation(Hertz-Pannier et al., 1997; Pardo and Fox, 1993) orsingle-word semantic decision task (Binder et al., 1996);in the latter case, lateralization was first evaluated innormal subjects (Binder et al., 1995). These studiesresulted in a good correlation between the two meth-ods, but the effect of functional dominance in terms ofits anatomofunctional organization and variability re-mains to be investigated.

The aim of the present work was thus to investigatethe anatomofunctional support of hemispheric domi-nance for language comprehension. Within this contextLH, who constitute a heterogeneous population with anabsence of clear relationship between manual prefer-ence and hemispheric dominance for language (Bentonet al., 1962; Hecaen et al., 1981; Hecaen and Sauguet,1971), represent a potential model for such an investiga-tion. To achieve this goal we measured normalizedregional cerebral blood flow (NrCBF) with positronemission tomography (PET) in five LH during a story-listening task and, in order to compare their meanactivation pattern to that of RH, have reanalyzed withSPM a previously published dataset obtained in 10 RH(Mazoyer et al., 1993). Moreover, to study the support oflanguage comprehension dominance anatomofunc-tional variability, we conducted an individual analysisin these five LH subjects.

MATERIALS AND METHODS

Data Analysis

Subject Selection

The subjects were 5 LH and 10 RH healthy Frenchmale graduate medical students, all having French astheir mother tongue; their mean age was 24 years(SD 5 2.2 years). Handedness was assessed using theEdinburgh inventory (Oldfield, 1971) and we derivedfrom the questionnaire a manual preference score(MPS) ranging from 2100 to 100, plus the preferred eyeand foot. The presence of familial sinistrality was alsoevaluated (see Table 1).

The selected LH considered themselves left handersand showed a clear leftward hand preference in all butLH5, together with left foot preference for all and lefteye preference for all but LH4. Familial sinistrality waspresent in two of the five subjects: LH4 had a left-handed father and LH5 had numerous left-handedsecond-degree relatives (one uncle and two cousins);familial sinistrality was unknown in one orphan sub-ject and absent in the remaining two subjects.

All RH MPS scores were higher than 66 and theirpreferred foot and eye were usually right except in

2 TZOURIO ET AL.

subject RH10 who used both feet to shoot a ball. RHfirst-degree relatives were RH except for RH3 as well asRH5 who each had a brother who could be ambidex-trous.

The subjects were free from cerebral abnormalitiesas assessed by their MRI brain scans.

The study was approved by the Atomic EnergyCommission Ethics Committee and all subjects gavetheir written informed consent.

Task Design

We chose to study the functional anatomy of lan-guage dominance during a story-listening task becausewe had demonstrated in a previous report that this taskelicits in RH large strongly leftward lateralized activa-tions in the temporal cortices (Mazoyer et al., 1993),allowing individual analysis (Levrier et al., 1993;Mazoyer et al., 1993).

The 15 subjects were instructed to passively butattentively listen to factual stories in French that weredesigned for the RH protocol (Mazoyer et al., 1993). Allstories, each lasting about 2 and a half minutes, wereread by a female speaker with comparable pitch, intona-tion, and volume (Text condition). Auditory stimuliwere presented binaurally over earphones, starting 45s before water injection. Different texts were used forthe replications. The texts were emotionally rich fac-tual stories taken from recent events. The first onedescribes a police misconduct during which a youngperson was murdered; the second concerns the harass-ment of a young couple, with a pregnant young woman,by a violent neighbor; the third one was about disquali-

fication during a ski competition. After listening tostories subjects were asked questions about the texts toensure that they understood the stories and thus paidattention to the task. A rest condition (Rest) served as areference and consisted in resting silently, eyes closed,without any particular instruction except to relax. Allexaminations were performed in total darkness.

Data Acquisition

Using PET and oxygen-15-labeled water, NrCBF wasmeasured six times in each subject, including tworeplications of the series of two conditions in the RHgroup (whose experimental protocol included anothertask not reported here) and three replications in the LHgroup (giving 20 and 15 pairs of measurements, respec-tively). The order of the presentation was determinedby a Latin square design in the RH group and wasrandomized by block in the LH group.

Two different PET cameras were used for NrCBFmeasurements. For the 10 RH, NrCBF was measuredon a time-of-flight PET system (Mazoyer et al., 1990)giving seven brain slices of 9-mm thickness every 12mm with an in-plane resolution of 5 mm. The images ofthe 5 LH were acquired on an ECAT 953B/31 PETcamera giving 31 contiguous brain slices of 3.375-mmthickness with an in-plane resolution of 5 mm21

(Mazoyer et al., 1991). All emission data were acquiredwith septa extended.

In both cases, following the intravenous bolus injec-tion of 60 mCi of 15O-labeled water a single 80-s scanwas reconstructed (including a correction for headattenuation using a measured transmission scan) witha Hanning filter of 0.5 mm21. The interval between twoinjections was 15 min.

Image Analysis

Average Analysis

Because of the difference in the z axis directionsampling of the two cameras that were used in eachgroup, our image analysis strategy for comparing theRH and LH groups aimed at bringing the averagedatasets to similar final resolution in the Talairachspace. Accordingly, we reanalyzed with SPM our RHdataset which was previously published with a volumeof interest analysis.

The t statistic corresponding to the comparison be-tween the Text and the Rest conditions was tested withthe three-dimensional version of SPM in each group ofsubjects (Friston et al., 1995). The original brain im-ages were transformed into the standard stereotaxicTalairach space (Talairach and Tournoux, 1988) usingthe same MNI template. A 12-mm Gaussian filter was

TABLE 1

Laterality Scores in the 15 Subjects Selected for the Study

Subjects Hand Foot Eye FS

RH1 75 R R 2RH2 100 R R 2RH3 75 R R 1RH4 100 * * 2RH5 100 * * 1RH6 81 R R 2RH7 81 R R 2RH8 100 R R 2RH9 100 * * 2RH10 66 B R 2LH1 250 L L *LH2 277 L L 2LH3 2100 L L 2LH4 2100 L R 1LH5 11 L L 1

Note. Edinburgh score is given for the preferred hand and rangesfrom 100 (exclusive right-hand utilization) to 2100 (exclusive left-hand utilization). Preferred eye and foot are given as right or left orboth (R, right; L, left; B, both; FS, familial sinistrality; * missingdata).

3STORY LISTENING IN RIGHT AND LEFT HANDERS

then applied on the images giving a 3D smoothness of12.4, 13.9, and 18 mm (in the x, y, and z axes, respec-tively) in the RH group and of 13.4, 15.4, and 14 mm inthe LH group.

Global CBF differences within and between subjectswere covaried out, and comparisons across conditionswere made by the way of t statistics. In order to keepthe larger field of view in each group, activations anddeactivations during the Text compared to the Rest ineach group are reported separately with a threshold setto P 5 0.001, uncorrected. After alignment in thestereotaxic space the number of resels was 324 and 566for RH and LH, respectively, with a voxel size of 2 mm3.The group comparison was performed on a commonvolume of 336 resels limited to slices located from 220to 140 mm in the z direction of the stereotaxic space,with a smoothness of 12.7 3 14.4 3 15.9 mm. TheANOVA design of SPM96 was used with thresholds setto 0.001 for the F value and to 0.01 for post hoc t.

Individual Analysis

Text minus Rest difference images were averagedand interpolated for each LH subject, in order togenerate isotropic voxels (size, 1.956 mm3). A firstanisotropic tridimensional Gaussian filter was firstapplied in order to obtain isotropic smoothness in the x,y, and z directions. On this fully tridimensional isotro-pic difference volume (in terms of voxel size and resolu-tion), a second isotropic tridimensional Gaussian filterwas applied, bringing the smoothness of the final image

to 9 mm. Filtered difference images were then normal-ized to 1 SD and thresholded at 2 SD. A 3D regiongrowing algorithm was applied in order to isolate andquantify 3D clusters showing a significant increase ofNrCBF. For each of these clusters, we computed thecoordinates of its weighted center of mass, its volumeexpressed in voxels, and its mean NrCBF value.

To proceed to the analysis of the relationships of theactivated areas with individual anatomy, the signifi-cant clusters were superimposed onto individual MRIafter 3D MRI to PET registration (Woods et al., 1993).The activated areas were described in each subjectrelative to major sulci in the temporal lobe that hadbeen identified by an expert using a method that wasdescribed elsewhere (Tzourio et al., 1997).

RESULTS

Right Handers Average Analysis

Activations during the Text-Listening Taskin RH (Table 2)

The SPM analysis of the RH confirmed the previouslyreported results of this dataset using an anatomicalvolume of interest (AVOI) analysis (Mazoyer et al.,1993). The comparison of text listening minus rest inRH showed a very large activation in terms of volumeand significance that encompassed the whole left supe-rior temporal and part of the middle temporal gyri,extending to the left planum temporale posteriorly, to

TABLE 2

Foci of Significant NrCBF Increases in Text Compared to Rest in the Group of 10 Right-Handed Subjects

Region size (voxels) Anatomical location of maximum voxel

Coordinates

Z score DCBFx y z

8750 L mid temporal 260 214 24 7.44 10.5L mid temporal 258 2 28 7.37 9.5L sup temporal (BA 42) 254 226 8 7.36 10L planum temporale (post BA 22) 262 228 8 7.22 10L Heschl gyrus (BA 41) 240 230 16 6.30 7L planum temporale (post BA 22) 260 252 18 6.15 6L amygdala 220 26 28 5.00 4L temporal pole (BA 38) 230 8 222 4.71 5L inf frontal gyrus (BA 45) 246 30 2 4.34 4L inf frontal gyrus (BA 44) 262 14 18 3.85 3.5

4178 R planum temporale (post BA 22) 50 232 6 7.02 7R sup temporal gyrus (BA 22) 54 214 2 6.84 10R sup temporal gyrus (BA 22) 58 22 22 6.82 8R Heschl gyrus (BA 41) 46 228 12 6.45 6

19 R temporal pole (area 38) 48 8 218 5.85 6R temporal pole (area 38) 36 12 222 5.47 5

4 L thalamus 212 232 6 4.04 4

Note. Anatomical localization of the maximum Z-score voxels is given as stereotaxic coordinates in mm. Uncorrected significance level wasset at P , 0.001 (Z score . 3.09; L, left; R, right; sup, superior; mid, middle; inf, inferior; post, posterior; BA, Brodmann’s area).

4 TZOURIO ET AL.

the left amygdala internally, and to the temporal poleanteriorly. This volume of activated pixels includedBroca’s area, with two maxima, one in the pars triangu-laris and the other in the pars opercularis of the leftinferior frontal gyrus (see Fig. 1).

In the right temporal cortex, a large area was acti-vated but was less than half of the volume of thecorresponding left-hemisphere temporal cortex activa-tion. It included the whole superior temporal gyruswith the temporal pole and the planum temporale butwithout any extension toward the right middle tempo-ral gyrus nor toward the right inferior frontal gyrus. Asignificant activation was observed in the left thala-mus.

Deactivations during the Text-Listening Taskin RH (Table 3)

Also, we were able to describe deactivations thatwere not previously reported. Deactivations duringText in right handers were asymmetrical, favoring theright hemisphere, with two main locations: frontal andparietal. The main frontal deactivations were observedin the right middle frontal gyrus and in the middlefrontal sulcus in front of the inferior frontal gyrus.

In the posterior part of the brain, deactivations werelocated in the right posterior cingulate and the rightintraparietal sulcus extending to the superior occipital,in the right inferior temporal cortex, near the occipi-totemporal junction and extending to the fusiformgyrus, and in the precuneus. In the left hemisphere asmall deactivation was located in the supramarginalisgyrus.

Left Handers Average Analysis

Activations during the Text-Listening Taskin LH (Table 4)

Subtracting the Rest condition from the text-listen-ing task in the LH group showed almost symmetricalactivations in the temporal cortex (see Fig. 2). Thelargest activation was, as in RH, located in the leftsuperior temporal and included the whole superiortemporal gyrus with the left temporal pole, with themiddle temporal gyrus, and extending toward the leftinferior frontal gyrus including Broca’s area and thepars orbitaris of this gyrus.

The second set of activated voxels was of similarvolume and covered the whole right superior temporalgyrus extending toward the right superior temporalsulcus and the middle temporal and included thetemporal pole. The Z scores for the two first maximawere similar to that for the left corresponding voxelswhich were located in the homologous regions of theright superior temporal gyrus (BA 22).

FIG. 1. Statistical parametric maps of the 10 right handers (Npairs 5 20) corresponding to the story-listening versus rest compari-son activations (top) and deactivations (bottom). Z volumes wereprojected in three orthogonal directions, sagittal, coronal, and axial,and thresholded at Z0 5 3.1 (P , 0.001, uncorrected for multiplecomparisons). Stereotactic coordinates of local maxima within theactivated areas are given in Tables 2 and 3.


The left medial frontal gyrus (BA 9) was activatedand a second medial frontal spot was observed in theorbital part of the frontal gyrus.

Deactivations during the Text-Listening Taskin LH (Table 5)

In the LH group deactivations were located, as in theRH group, in middle frontal and parietal regions andinferior temporal gyrus but appeared symmetrically inboth hemispheres.

In the posterior part of the brain, the pattern ofdeactivations involved bilaterally the supramarginalisgyri and medially, the precuneus and the cingulategyrus. In the temporal lobe, bilateral inferior temporalgyri NrCBF decreases were present.

In the frontal lobe, bilateral superior frontal sulciand middle frontal gyri were deactivated with, on theleft, a deactivation of the middle frontal sulcus follow-ing the sulcus’ route, just in front of Broca’s area.

In other words, the deactivation patterns were very

TABLE 4

Foci of Significant NrCBF Increases in Text Compared to Rest in Five Left Handers

Region size(voxels) Anatomical location of maximum voxel

Coordinates

Z score DCBFx y z

6203 L sup temporal (BA 22) 260 214 4 6.86 10L sup temporal (BA 22) 256 224 4 6.86 10L temporal pole (BA 38) 252 4 218 6.06 10L temporal pole (BA 38) 236 14 230 4.43 5L inf frontal gyrus (BA 45) 252 26 4 4.42 4.5L mid temporal gyrus 244 234 24 3.67 4.5L inf frontal gyrus (BA 47) 244 24 210 3.38 4L inf parietal 248 258 24 3.24 4

5398 R sup temporal (BA 22) 62 212 2 6.80 10R sup temporal (BA 22) 58 22 0 6.57 8R sup temporal sulcus/middle temporal gyrus 56 226 6 6.50 9R temporal pole (BA 38) 50 10 226 5.29 8R temporal pole (BA 38) 34 18 234 4.41 5R Heschl gyrus (BA 41) 34 232 12 3.77 3

39 L orbital frontal 24 54 216 3.93 348 Left medial frontal gyrus 28 58 22 3.44 4

Note. Anatomical localization of maximum Z-score voxels is given as stereotaxic coordinates in mm. Uncorrected significance level was set atP , 0.001 (Z score . 3.09; L, left; R, right; sup, superior; mid, middle; inf, inferior).

TABLE 3

Foci of Significant NrCBF Decreases in Text Compared to Rest in the 10 Right-Handed Subjects


Coordinates

Z score DCBFx y z

1100 R mid frontal sulcus 42 46 10 5.68 26R mid frontal gyrus 42 50 22 5.34 25R mid frontal gyrus 50 34 26 3.54 24

1048 R post cingulate 16 254 20 5.29 25R intraparietal sulcus 36 272 20 4.90 24R sup occipital gyrus 30 274 34 4.38 23

577 R mid temporal sulcus 54 248 28 4.91 24.5R fusiform gyrus 50 238 220 3.91 23R fusiform gyrus 44 232 220 3.89 23.5

136 R supramarginalis gyrus 62 226 28 4.70 251018 L precuneus 28 270 36 4.68 25

R precuneus 8 268 40 4.63 23191 R sup frontal gyrus (area 10) 14 68 22 4.63 2461 L supramarginalis gyrus 258 222 32 4.43 23

Note. Anatomical localization of maximum Z-score voxels is given as stereotaxic coordinates in mm. Uncorrected significance level was set atP , 0.001 (Z score . 3.09; L, left; R, right; sup, superior; mid, middle; inf, inferior; post, posterior).

6 TZOURIO ET AL.

close to those of RH, but with additional involvement inthe left hemisphere of middle frontal, supramarginalis,and inferior temporal gyri.

Comparison of Activations during the ListeningTask: RH vs LH

Larger Activations in Right Handers Than in LeftHanders (Fig. 3, Top, Table 6)

This contrast revealed a greater left hemisphereinvolvement during the text-listening task in RH. Afirst area was detected in the left planum temporaleand left superior temporal gyrus in which the between-group difference was due to larger activation in RHthan in LH.

A second region was significantly detected in the leftsuperior temporal gyrus and was located in the ante-rior part of the gyrus including the temporal pole. Inthe temporal pole at the local maxima the NrCBFincrease in RH during story listening compared to restwas double that of LH.

In the left amygdala the observed between-groupdifference was due to the fact that while RH showedNrCBF increase in this region, LH had no activation orsmall NrCBF decreases.

In the orbital part of the left inferior frontal gyrus(BA 47) significantly larger activations were observedin RH, with an absence of increase or even a smallNrCBF decrease in LH.

Larger Activations in Left Handers versus RightHanders (Fig. 3, Bottom, Table 6)

This contrast revealed two right middle temporalregions with higher activations during the listeningtask in LH than in RH. The first one, located in theanterior and superior part of the right middle temporalgyrus, near the superior temporal sulcus, was due to alarge activation in LH, while no activation or a smallNrCBF decrease was observed in RH. In contrast, thesecond, located in the posterior and inferior part of theright middle temporal gyrus, near the inferior temporaland the occipital cortex, was due to greater deactiva-tions in RH than in LH.

Finally, the left precuneus was also more deactivatedin RH than in LH.

Individual Analysis in Left Handers

The individual analysis of activation image in LHdemonstrated that temporal regions involved duringtext listening were in all subjects composed of theHeschl’s gyris, the planum temporale, and the temporalpoles (see Fig. 4). LH1 showed a pattern close to thoseof RH as established with the average analysis of the 10RH, activations favoring the left superior temporalgyrus in terms of intensity and extent, encompassing

the left middle temporal gyrus and associated with aBroca activation (visible on slice 3 from the left). A leftmedian frontal activation was also detected. LH2 pre-sented a clear leftward asymmetry in the superiortemporal gyrus including the temporal poles, extendingto the left middle temporal, but an extension to theright middle temporal gyrus was also detected. A leftmedian frontal gyrus activation was observed as wellas an activation of the left inferior frontal gyrus. LH3temporal activations were almost symmetrical togetherwith a bilateral activation of the cerebellum. The rightprecentral gyrus and thalamus were also activated inthis subject. LH4 showed a bilateral implication of thesuperior and middle temporal gyri. An activation lo-cated in the left median frontal gyrus was present. NoBroca’s area nor cerebellar activation could be detected.LH5 showed a clear rightward asymmetry favoring theright superior and middle temporal with bilateralinferior frontal activation and a large left cerebellumparticipation.

In summary at the temporal level, two subjects wereclearly leftward lateralized (LH1, LH2), two were sym-metrical (LH3, LH4), and one showed a rightwardasymmetry. In addition, inferior frontal gyrus activa-tion was detected on the left in four subjects (LH1, LH2upper part, LH3, LH5) with a rightward component inLH5. Right cerebellar cortex activations were observedin LH1, LH3, and LH5 together with leftward activa-tions in LH3 and LH5, the asymmetry favoring the leftin the last case.

DISCUSSION

Temporal Cortex Activations

The pattern of activations in the LH group includedthe same network of regions as in the RH group but thelateralization was strikingly different: in LH the extentof the activated areas in the temporal cortex during thetext-listening task were 30% higher in the left hemi-sphere (using the same field of view and smoothness inboth groups L, 6884; R, 5002 voxels), while in RH thevolume of activation was 75% larger in the left hemi-sphere (L, 8477; R, 4833 voxels). Amplitudes of NrCBFincreases were similar in both groups. This result inRH confirms our previous AVOI study in which statisti-cally significant leftward asymmetry was described inthe temporal cortex and Broca’s area (Mazoyer et al.,1993). Although a statistical direct comparison of asym-metry is not possible with SPM, the lesser asymmetryin terms of the volume of activated resels in LHindicates that LH as a group have a lesser temporalfunctional asymmetry than RH, which is in agreementwith what had been suggested by authors studyingaphasia in LH (Hecaen et al., 1981). Whatever themethod used to evaluate functional dominance, there isa consensus that RH show an important leftward


FIG. 2. Statistical parametric maps of the 5 left handers (N pairs 5 15) corresponding to the story-listening versus Rest comparison.activations (top) and deactivations (bottom). Z volumes were projected in three orthogonal directions, sagittal, coronal, and axial, andthresholded at Z0 5 3.1 (P , 0.001, uncorrected for multiple comparisons). Stereotactic coordinates of local maxima within the activated areasare given in Tables 4 and 5.

FIG. 3. Statistical parametric maps of the between-group activations comparison during story listening versus Rest. Right handers versusleft handers comparison (top) and left handers versus right handers (bottom). After an ANOVA for group comparison with an F value set at0.001, the Z volumes were projected in three orthogonal directions, sagittal, coronal, and axial, and thresholded at Z0 5 2.33 (P , 0.01, posthoct tests). Stereotactic coordinates of local maxima within the activated areas are given in Table 6.

8 TZOURIO ET AL.

FIG. 4. Results of the individual detection of activation in the 5 LH. Areas of detected activation are copied onto the corresponding MRIslice after MRI to PET coregistration; all images are given with the same scale from 0 to 60% of activation. Individual identification ofanatomical landmarks was conducted in each subject thanks to a 3D software (Voxtool, General Electric) that allows 3D reconstruction andreslicing of axial MRI slices that were acquired for each subject. White arrows indicate the sylvian fissure, yellow arrows the superior temporalsulcus, yellow-green arrows the middle temporal sulcus, and red arrows the Rolando sulcus. Each row corresponds to one of the LH: from LH1(top) to LH5 (bottom). From left to right are given lower to upper slices. Left is on the left side of the image. One may observe that although thefirst two subjects show a leftward asymmetry, LH3 and LH4 show language comprehension ambilaterality and LH5 a rightward dominance.


language lateralization. In the present study this asym-metry is supported by a greater implication of the lefttemporal cortex during auditory speech comprehen-sion. As a matter of fact, aphasia studies have shownthat RH are characterized by significantly more fre-quent verbal comprehension disorders after lesion of

the left hemisphere than LH (Hecaen and Sauguet,1971).

The comparison of RH and LH activations allowed usto characterize this functional asymmetry difference: inthe temporal cortex, the RH activate the left hemi-sphere more, in particular the left planum temporale

TABLE 5

Foci of Significant NrCBF Decreases in Text Compared to Rest in the Five Left Handers

Region size Anatomical location of maximum voxel

Coordinates

Z score DCBFx y z

605 L supramarginalis gyrus 258 228 34 4.80 24L supramarginalis gyrus 250 244 46 4.59 24L supramarginalis gyrus 236 236 48 4.04 23.5

122 L inf temporal gyrus 250 260 210 4.80 241900 L precuneus 210 258 66 4.77 23.5

R median cingulate 4 236 48 4.63 23L paracentral lobule 28 234 52 4.57 23

527 L mid frontal gyrus 244 30 32 4.39 24.5L mid frontal sulcus 236 32 20 4.39 24L mid frontal sulcus 238 46 8 4.07 24

573 R supramarginalis gyrus 62 232 34 4.19 23.5R supramarginalis gyrus 50 252 48 3.89 24R supramarginalis gyrus 54 238 42 3.80 23.5

116 L sup frontal gyrus (area 6) 222 2 66 3.92 23.539 R mid frontal gyrus (area 6) 38 28 36 3.81 23.562 R mid frontal gyrus (area 6) 26 8 60 3.78 24

103 R inf temporal gyrus 56 236 222 3.75 2493 R mid frontal sulcus 48 42 8 3.67 23

Note. Anatomical localization of the maximum Z-score voxels is given as stereotaxic coordinates in mm. Uncorrected significance level wasset at P , 0.001 (Z score . 3.09; L, left; R, right; sup, superior; mid, middle; inf, inferior).

TABLE 6

Comparison of Right and Left Handers’ NrCBF Variations during Text Compared to Rest


Coordinates

Z score

DCBF

x y z RH LH

DNrCBF in right handers . DNrCBF in left handers

245 L planum temporale (post BA 22) 268 236 8 3.48 18 14L sup temporal (BA 42) 266 222 16 2.77 15 11

96 L amygdala region 214 22 214 3.36 13 21.5L amygdala region 222 210 24 3.17 13 0

110 L inf frontal orbital (BA 47) 234 28 214 3.28 14 21L inf frontal orbital (BA 47) 230 10 218 3.14 15.5 11

162 L sup temporal (BA 22) 246 12 0 2.98 15 0L temporal pole (BA 38) 256 12 210 2.45 110 15

DNrCBF in left handers . DNrCBF in right handers

262 R mid/inf temporal gyrus 50 246 28 3.99 25 0R mid temporal gyrus 46 252 6 3.77 22.5 12

157 L precuneus 26 268 34 3.59 25 20.5128 R sup temporal sulcus/mid temporal 44 248 10 3.42 20.5 14

R mid temporal/sup temporal sulcus 52 246 6 3.25 0 15

Note. Anatomical localization of the maximum Z-score voxels is given as stereotaxic coordinates in mm (F , 0.001; P , 0.01; RH, righthanders; LH, left handers; L, left; R, right; sup, superior; inf, inferior).

10 TZOURIO ET AL.

and the left temporal pole, while LH activate anadditional right hemisphere region in the middle tempo-ral.

Planum Temporale

The greater NrCBF activation of the planum tempo-rale in RH is congruent with anatomical studies thatshowed a leftward asymmetry of the planum temporalein RH (Geschwind and Levitsky, 1968), which wasconfirmed by in vivo MRI anatomical studies (Stein-metz, 1996) together with the evidence that LH presenta decrease of this asymmetry (Steinmetz et al., 1991).From these structural studies, the hypothesis wasraised that planum temporale asymmetry could reflectthe left hemisphere functional dominance for language.With functional MRI, Binder et al. (1996) revisited thisidea by showing an absence of additional activation inthe planum temporale when comparing auditory wordsversus tone sequences processing. However, this lastresult was challenged by a recent sentence-processingstudy, using the same technique, that showed an in-crease of the amount of activation in the superiortemporal gyrus, including the planum temporale, withsentence complexity (Just et al., 1996). This auditory-associative area, corresponding to the cytoarchitectonicarea Tpt, encloses the posterior part of BA 22 (Gala-burda and Sanides, 1980). As numerous ERP (forreview see Naatanen and Picton, 1987) and MEG(Hillyard et al., 1995) studies have shown, it is impli-cated in the early processing of sounds (Celesia, 1976;Liegeois-Chauvel et al., 1994; Pantev et al., 1994) andselective auditory attention. The left-hemisphere domi-nance for speech could in part rely on this earlyprocessing of complex language sounds in the planumtemporale and adjacent regions. A default in the left-hemisphere dominance for this processing could be atthe origin of language developmental pathology such asdysphasia (Tallal et al., 1993, 1996) which was sup-ported by the observation of decreased planum tempo-rale asymmetry in dysphasics (Jerningan et al., 1991)and dyslexics (Larsen et al., 1990). The results of thepresent study support the idea that the larger leftplanum temporale could indeed reflect left-hemispheredominance for language comprehension, since it ismore activated in RH who show a high incidence ofleft-hemisphere functional dominance for language. Asa matter of fact, we demonstrated in a conjoint study acorrelation between the left planum temporale surfaceand the amount of left superior temporal gyrus activa-tion during story listening (Tzourio et al., 1998).

Temporal Poles

We confirm here an original finding of our early RHstudy of story listening (Mazoyer et al., 1993), namelythe implication of the temporal poles during continuous

speech processing. The temporal poles’ putative role, ifone refers to neuropsychological studies, is to be part ofthe memory component implicated in the grasping ofthe coherence of the text. Indeed, Milner has shown(Milner, 1958) that after left anterior temporalectomypatients had an impoverished recall of stories, despiteintact sentence comprehension and working-memorycapacities (Frisk and Milner, 1990). Further functionalimaging studies have confirmed in part this hypothesissince bilateral activations of the temporal poles havebeen described during the free recall of novel and ofpracticed narratives (Andreasen et al., 1995a), as wellas during the free recall of word lists (Andreasen et al.,1995c), but without any involvement during word-recognition memory task (Andreasen et al., 1995b). Theimplication of temporal poles during listening to storiesseems specific to the mother tongue, since no implica-tion of the temporal poles was detected during factualstory listening delivered auditorily in an unknown oracquired language (Mazoyer et al., 1993; Perani et al.,1996).

The left temporal pole had also been implicated invisually presented sentence processing (Bavelier et al.,1997; Bottini et al., 1994) and could thus be part of thesyntactic system. Indeed, bilateral temporal pole activa-tion was observed during nonautobiographic episodicmemory retrieval based on listening to sentences, astudy design in which both sentence processing andmemory were implicated (Fink et al., 1996). One shouldnote, however, that the right temporal pole, togetherwith the right amygdala, was more activated whensentences referred to autobiographic memory with agreater affective charge (Braak et al., 1996). Bilateraltemporal pole activations, with an asymmetry favoringthe right side, were also observed during externallygenerated emotions whatever the media: a movie pre-sentation (Lane et al., 1997a; Reiman et al., 1997), theview of emotional words (see Fig. 2 of Beauregard et al.,1997), or the recall of internally generated emotion(Reiman et al., 1997).

It seems thus that the temporal poles, anatomicallyclose to the amygadala and made of an archaic cortexpart of the limbic system (Mesulam, 1985), could bepart of the memory system for sentences and continu-ous speech implicated in the processing of the emo-tional component of language such as that embedded inthe mother tongue. The temporal pole showed a left-ward dominance for language as indicated by the factthat it is implicated more during text listening in RHthan in LH, while the right temporal pole could bedominant for the processing of word- or story-relatedevoked emotions.

Middle Temporal

Another striking result of the present study is theactivation of a region of the right middle temporal


gyrus, near the superior temporal sulcus, during thelanguage task in LH only. Although the left middletemporal gyrus has been repeatedly implicated duringvarious language tasks (Fiez et al., 1996; Zatorre et al.,1992), the right posterior middle temporal had neverbeen, to our knowledge, implicated during auditorylanguage task in RH. This result indicates in LH aparticipation of the right hemisphere in auditory lan-guage comprehension, which reinforces the conceptthat their ambilaterality is particularly marked forcomprehension and is consistent with previous aphasiastudies showing that LH with right-hemisphere poste-rior lesion have more frequent language deficits thanRH (Hecaen and Sauguet, 1971).

A second right middle temporal region more acti-vated in LH was located in the posterior part of theright middle temporal and inferior temporal gyrus nearthe occipital lobe and corresponds to a region consid-ered a visual field belonging to the ventral route: it hadbeen found activated in RH during the learning andrecognition of colored patterns (Roland and Gulyas1995), the processing of new versus old pictures (Tulv-ing et al., 1996), passive perception of visual motion(Watson et al., 1993), motion–form discrimination (Gul-yas et al., 1994), and retrieving and encoding objectfeatures compared to object location (Owen et al., 1996).In our study, the difference between RH and LH wasdue to a greater deactivation in RH during storylistening; a deactivation of this region during storylistening tasks has also been described in a recentstudy (Andreasen et al., 1995a). As will be discussed inthe deactivation section, this lower deactivation in LHcould reflect a lesser lateralization for visual processingof objects.

Broca’s Area

The implication of Broca’s area during text listeningin RH confirms what we already described in ourprevious report (Mazoyer et al., 1993) and is in agree-ment with other reports (Perani et al., 1996). Thisresult also fits well with aphasia studies that havedemonstrated that Broca’s area lesions may result inboth language production and comprehension deficits(Damasio, 1992). Broca’s area, as was first suggested byPetersen, could be implicated in semantic processing(Petersen et al., 1988), a hypothesis that was confirmedby the fact that Broca is activated during passivelistening of list of words (Mazoyer et al., 1993; Price etal., 1996) and during language search, independent ofwhether the search is guided by phonological or seman-tic cues (Klein et al., 1995). The fact that Broca isactivated during visually presented complex sentenceprocessing (Stromswold et al., 1996), as well as duringtext listening, indicates that it could be implicated inboth semantic and syntactic processing.

In the present study, no difference was observed in

Broca’s area activation between RH and LH. As amatter of fact, aphasia studies on LH told us thattroubles in naming in LH always follow left-hemi-sphere lesions (Hecaen et al., 1981). This could indicatea different dominance pattern in frontal and temporalcerebral areas during language tasks. However, indi-vidual results showed that LH5, who demonstrates aclear rightward lateralization in the temporal lobe, hadbilateral inferior frontal activations, which points to-ward a participation of the right inferior frontal gyruswhich may have been overlooked by the average analy-sis.

Medial Wall of the Hemispheres

Medial Frontal and Orbital Frontal

Two significant activations of the medial wall of theleft frontal were noted in LH, one in the medial frontalgyrus and one in the gyrus rectus. These activationswere present at lower statistical level in RH (medialfrontal 210, 248, 28; Z 5 3.71; volume, 137 voxels;orbital frontal 0, 52,216; Z 5 3.88; volume, 90 voxels),which explains why they did not show up in the LHminus RH comparison. The first activated area, corre-sponding to Brodmann’s area 9, is little documented infunctional-imaging studies. Neuropsychology assignsto the lesion of median frontal and orbitofrontal regiona defect in processing of emotion (Damasio et al., 1994).As a matter of fact, its activation has been observed,together with orbital frontal, amygdala, and thalamusactivations, during emotion processing (Lane et al.,1997a,b; Reiman et al., 1997), and again together withthe orbital frontal, during the recall of emotional words(Beauregard et al., 1997), as well as during the recall ofpersonal events from the past, a condition rich inemotion (Andreasen et al., 1995a). As underlined al-ready in our study, the stories subjects listened to wererich in emotional content, which could explain theimplication of a network of regions for both linguisticand emotion processing, the latter being very likely toinvolve these median frontal and orbitofrontal regions.The absence of difference between LH and RH for theseactivations indicates that they do not contribute to thelateralization of language.

Amygdala

In the RH group, additional regions were detectedwith the SPM analysis, namely the left amygdala andthe left thalamus, small regions that were overlookedusing the AVOI method. The activation of the leftamygdala region could be related, together with theactivation of the very near temporal pole, to the encod-ing of the factual stories relying on the processing oftheir emotional content. As a matter of fact, the amyg-dala is known to be involved in the acquisition andexpression of emotional memory (for review see Phelps

12 TZOURIO ET AL.

and Anderson, 1997). Numerous functional-imagingstudies dealing with emotion have demonstrated amyg-dala involvement in different cognitive tasks includingemotional processing: face expression (Breiter et al.,1996; Morris et al., 1996), emotion self-rating (Schneideret al., 1995), stress of a difficult cognitive task (Schneideret al., 1996), mental imagery of a stressful situation(Shin et al., 1997), and aversive olfactory stimulation(Zald and Pardo, 1997). The amygdala is consideredpart of the memory systems (Squire and Zola, 1996), inparticular the memory of emotions (Cahill et al., 1996).The leftward lateralization of this activation in thepresent study would indicate the existence of a special-ization for encoding of language-related emotions. Infact, the amygdala does not seem to be implicated inverbal memory free of emotion since left amygdaladeactivation has been reported during practiced wordrecall (Andreasen et al., 1995c).

Thalamus

In LH, no activation of the left thalamus was ob-served, while an activation in its posterior part waspresent in the RH group. This activation could also berelated to the memory-processing component of thestory-listening task. Indeed, recordings from long-termelectrodes have shown asymmetries of neuronal activ-ity favoring the left thalamus during word recognition(Bechtereva et al., 1992; Bechtereva and Medvedev,1990). Moreover, the thalamus has been involved dur-ing memorization of words (Grasby et al., 1994) andfree recall of complex narratives (Andreasen et al.,1995a), albeit in a more anterior location. As a matter offact, although thalamic lesions can conduct to aphasia,anterior nucleus damage is necessary for the appear-ance of aphasia (Damasio, 1992), and this posteriorthalamic activation is unlikely to reflect the left thala-mus involvement during language processing.

One should note, however, that bilateral thalamusactivations, located at coordinates very close to those ofthe present study, were observed during the processingof emotions together with medial and orbitofrontal andamygdala activations (Lane et al., 1997a; Reiman et al.,1997), indicating that this activation could reflect theimplication of the thalamus in the emotion processingnetwork. This does not explain, however, why no NrCBFincrease was observed in this region in LH and thusneeds further documentation.

Deactivations

In both groups deactivations were observed in thesame regions: occipital, parietal, and posterior cingu-late cortices; inferior temporal; and middle frontal.These deactivations can be interpreted in two differentways, either as activations during the Rest condition assuggested by N. Andreasen (Andreasen et al., 1995d) or

as deactivations specific to auditory language tasks. Areview of the literature in regard to the Rest conditionshows, indeed, that the retrosplenial regions, namelyposterior cingulate and precuneus, show systematicallylarger values during this condition (Andreasen et al.,1995a). This finding is probably related to the episodicmemory component of the Rest condition, the retrosple-nial regions having been frequently implicated duringepisodic memory task implicating verbal stimuli (Grasbyet al., 1993) or visual, including mental images, stimuli(Fletcher et al., 1995; Kosslyn et al., 1993; Mellet et al.,1996; Petit et al., 1996; Roland and Gulyas, 1995).

Regarding the inferior temporal and occipital re-gions, deactivations of visual cortices during auditorylanguage tasks have already been described (Fink etal., 1996; Mellet et al., 1996) as well as deactivations oftemporal language areas during visual tasks (Dupontet al., 1993; Petit et al., 1997). Such cross-modalinhibition has also been shown with somatosensorystimulations during which visual-area NrCBF de-creases have been observed (Kawashima et al., 1995).The same kind of explanation could be proposed for theright supramarginalis gyrus, part of the inferior pari-etal, a region involved in visuospatial processing andvisuospatial attention and that has already been de-scribed as particularly deactivated during languagetasks (Shulman et al., 1997).

The major difference between the two groups relieson the observation that deactivations are rightwardlateralized in RH while they were bilateral and slightlyleftward lateralized in LH. This means that the left-hemisphere dominance for language implicates right-hemisphere inhibition of visuospatial areas, functionsthat are represented mainly in the right hemisphere inRH, while this cross-modal deactivation implicatesboth hemispheres in LH. This result is in accordancewith the studies conducted by Hecaen that showedmuch smaller differences in the comparison of left- andright-hemisphere syndromes associated with hemi-spheric lesions in left handers than in right handers,thereby establishing the existence of cerebral ambilat-erality in left handers for language that extends tospatial functions (Hecaen et al., 1981). The same au-thor also showed that in the left posterior hemisphericsyndrome in LH there were some elements usuallyobserved in lesions of the posterior right hemisphericsyndrome in RH, namely a spatial disorientation (He-caen and Ajuriaguerra, 1963). Accordingly, the bilateraldorsal route deactivations during text listening in LHwould then be a reflect of the ambilaterality of theirspatial function cerebral representation.

Relationship between Left Handednessand Functional Dominance

We observed in the individual analysis two LH with aleftward dominance and an anatomofunctional pattern


close to that of RH. But the three other subjects had apattern different from RH, with LH3 presenting sym-metrical activations and LH4 and LH5 a right temporaldominance. This significant participation of the righttemporal cortex in three LH weakens the claim ofKimura that the role of right hemisphere in speechfunction in most LH is negligible (Kimura, 1983). As amatter of fact the subjects we selected did not sufferfrom early left hemisphere injury.

No definitive conclusion can be drawn from this smallsample, and to characterize functional dominance vari-ability in LH and RH we will need to acquire largergroups of subjects. But this study demonstrated thatthis project is worthy and that functional imaging is,definitely, an ideal tool for noninvasive mapping offunctional dominance.

ACKNOWLEDGMENTS

We are deeply indebted to the Orsay radiochemistry staff forlabeled water production, to Monique Crouzel and Laurence Laurierfor data acquisition, to Marc Joliot and Dimitri Papathanassiou forthoughtful discussions, and to our colleagues from the Laboratoire dePsycholinguistique (Jacques Mehler, Director) for the tape recordingof the stories.

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Functional Anatomy of Dominance for Speech Comprehension in Left Handers vs Right Handers

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