Available online at www.sciencedirect.com

www.elsevier.com/locate/b&l

Brain & Language 106 (2008) 177–183

Functional topography of early periventricular brain lesionsin relation to cytoarchitectonic probabilistic maps

Martin Staudt a,b,*, Luca F. Ticini c, Wolfgang Grodd b, Ingeborg Krageloh-Mann a,Hans-Otto Karnath c

a Department of Pediatric Neurology and Developmental Medicine, University Children’s Hospital, Hoppe-Seyler-Str. 1, D-72076 Tubingen, Germanyb Section Experimental MR of the CNS, Department of Neuroradiology, Radiological Clinic, University of Tubingen, Tubingen, Germany

c Section Neuropsychology, Center for Neurology, Hertie-Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany

Accepted 13 January 2008Available online 13 February 2008

Abstract

Early periventricular brain lesions can not only cause cerebral palsy, but can also induce a reorganization of language. Here, we askedwhether these different functional consequences can be attributed to topographically distinct portions of the periventricular white matterdamage. Eight patients with pre- and perinatally acquired left-sided periventricular brain lesions underwent focal transcranial magneticstimulation to assess the integrity of cortico-spinal hand motor projections, and functional MRI to determine the hemispheric organi-zation of language production. MRI lesion-symptom mapping revealed that two distinct portions of the periventricular lesions were crit-ically involved in the disruption of cortico-spinal hand motor projections on the one hand and in the induction of languagereorganization into the contra-lesional right hemisphere on the other hand. Both regions are located in a position compatible withthe course of cortico-spinal/cortico-nuclear projections of the primary motor cortex in the periventricular white matter, as determinedby the stereotaxic probabilistic cytoarchitectonic atlas developed by the Julich group.� 2008 Elsevier Inc. All rights reserved.

Keywords: Early brain lesions; Reorganization; Cerebral palsy; Functional MRI; Transcranial magnetic stimulation; Cortico-spinal tract

1. Introduction

Periventricular brain lesions are among the most fre-quent causes for cerebral palsy (Ashwal et al, 2004). Thistype of lesion typically occurs during the early 3rd trimesterof pregnancy, either as intrauterine insults or as complica-tions of premature birth (Krageloh-Mann, 2004; Staudtet al, 2004). The motor dysfunction of patients with suchlesions is commonly believed to result from structural dam-age to cortico-spinal projections in the periventricularwhite matter (Banker & Larroche, 1962). Indeed, severaltranscranial magnetic stimulation (TMS) studies couldshow that in patients with large unilateral periventricularlesions, TMS of the affected hemisphere did not elicit

0093-934X/$ - see front matter � 2008 Elsevier Inc. All rights reserved.

doi:10.1016/j.bandl.2008.01.007

* Corresponding author. Fax: +49 7071 295473.E-mail address: martin.staudt@med.uni-tuebingen.de (M. Staudt).

motor responses in target muscles of the (contralateral)paretic hand, indicating that the lesion had disrupted thenormal crossed cortico-spinal projections from the affectedhemisphere (Carr, Harrison, Evans, & Stephens, 1993;Maegaki et al, 1997; Nezu, Kimura, Takeshita, & Tanaka,1999; Staudt et al, 2002a).

Periventricular lesions, however, do not only affect themotor system, but can—in the case of left-sided lesions—also induce a reorganization of productive language func-tions into the contralesional, right hemisphere (Staudtet al, 2001, 2002b). Right-hemispheric language organiza-tion induced by early left-sided brain lesions typicallyachieves normal language functions (Table 1; Muter, Tay-lor, & Vargha-Khadem, 1997; Staudt et al., 2002b), but cancompromise right-hemispheric functions such as visuo-spa-tial abilities (Lidzba, Staudt, Wilke, & Krageloh-Mann,2006). To observe right-hemispheric organization in our

Tab

le1

Pat

ien

tsd

emo

grap

hic

and

clin

ical

dat

a,p

re-

and

per

inat

alh

isto

ry,

resu

lts

of

the

TM

Sin

vest

igat

ion

(pre

serv

edvs

.d

isru

pte

dco

rtic

o-s

pin

alp

roje

ctio

ns

fro

mth

eaff

ecte

dh

emis

ph

ere

toth

ep

aret

ich

and

),o

fth

efM

RI

inve

stig

atio

n[n

um

ber

of

acti

vate

dvo

xels

inle

ft(L

)an

dri

ght

(R)

hem

isp

her

e;S

PM

99,

p<

0.05

corr

ecte

dfo

rm

ult

iple

com

par

iso

ns

atvo

xel

leve

l],

and

verb

alIQ

sco

res

(usi

ng

the

Ger

man

adap

tati

on

of

the

Wec

hsl

ersc

ale;

Tew

es,

1994

)

Pt

Age

(y)

Sex

Pre

mat

uri

ty(G

A)

Bir

thw

eigh

t(g

)P

re-

and

per

inat

alco

mp

lica

tio

ns

Han

ded

nes

sH

and

mo

tor

dys

fun

ctio

nC

ort

ico

-sp

inal

trac

tin

tegr

ity

(TM

S)

Lan

guag

eL

ater

alit

y(f

MR

I)N

um

ber

of

acti

vate

dvo

xels

Ver

bal

IQ

LR

123

m–

3800

Cer

clag

eat

33w

GA

L1

Pre

serv

edL

>R

295

9512

92

17m

–36

50–

L1

Pre

serv

edL

>R

129

9093

820

f–

3040

–L

1P

rese

rved

R>

L11

247

290

522

m33

w23

80–

L2

Pre

serv

edR

>L

4417

413

63

20f

–33

40–

L2

Dis

rup

ted

L>

R10

069

93

421

f–

3400

–L

2n

/aR

>L

6536

3n

/a6

18m

–23

00A

bn

orm

alC

TG

,C

SL

3D

isru

pte

dR

>L

021

112

725

f36

w25

00–

L2

Dis

rup

ted

R>

L10

645

292

Han

dm

oto

rd

ysfu

nct

ion

was

grad

edw

ith

the

seq

uen

tial

fin

ger

op

po

siti

on

task

asre

po

rted

pre

vio

usl

y(S

tau

dt

etal

,20

02a)

,w

ith

1=

no

rmal

per

form

ance

;2

=sl

ow

and

/or

inco

mp

lete

per

form

ance

;3

=in

abil

ity

top

erfo

rman

yin

dep

end

ent

fin

ger

mo

vem

ents

,b

ut

wit

ha

pre

serv

edgr

asp

fun

ctio

n.

Th

ep

atie

nts

are

nu

mb

ered

asin

ou

rp

revi

ou

sp

ub

lica

tio

n(S

tau

dt

etal

,20

01),

bu

tso

rted

acco

rdin

gto

the

TM

San

dfM

RI

fin

din

gs.

GA

,ge

stat

ion

alag

e;C

TG

,ca

rdio

toco

gram

;C

S,

Cae

sare

anse

ctio

n;

w,

wee

ks;

n/a

,n

ot

avai

lab

le.

178 M. Staudt et al. / Brain & Language 106 (2008) 177–183

patients with periventricular lesions was unexpected insofaras these lesions typically leave cortical language zones—atleast macroscopically—intact. As a possible explanationfor this phenomenon, we suggested that structural damageto facial motor projections of the left hemisphere, withtheir well-known relevance for articulation (Wildgruber,Ackermann, Klose, Kardatzki, & Grodd, 1996), mightinduce this reorganization of language.

In the current study, we addressed this issue by askingwhether specific, topographically distinct locations of peri-ventricular lesions are critical for (a) the disruption of handmotor projections of the cortico-spinal tract and (b) theinduction of language reorganization. We did this by takingadvantage of previously collected and published data on thiswell-described sample of patients (Staudt et al., 2001, 2002a).

2. Materials and methods

2.1. Subjects

Eight patients (4 women; age range, 17–25 years) withcongenital right hemiparesis due to left-sided periventricu-lar brain lesions were included (Table 1). Informed writtenconsent and approval from the local ethics committee wereobtained.

In a previous study (Staudt et al., 2002a), seven of thesepatients had undergone focal TMS to determine whetherthe affected hemisphere still possessed crossed cortico-spinal projections to the paretic hand. Four patientsshowed preserved crossed projections to the paretic hand,three did not. No TMS data were available for patient#4 (Table 1); the subject thus was excluded from the anal-ysis on cortico-spinal projections (see below).

In a further study (Staudt et al., 2001), all but onepatient (#8) from the current sample were examined withrespect to right- and left-hemisphere activation duringspeech by functional MRI during silent word generation:The subjects were instructed to silently generate wordchains, the first word starting with a letter given by theexaminer, the next word starting with the last letter ofthe previous word, and so on. The procedure, which wasapplied in an identical manner in patient #8, is describedin detail in Staudt et al. (2001). The lateralization of lan-guage production in this group of patients was found tobe highly variable (Table 1)—in contrast to healthy right-handed controls, who showed a consistent and strong left-ward asymmetry of activation. Due to the overall samplesize, we dichotomized the patient group into those present-ing a higher number of fMRI activated voxels in the leftversus the right hemisphere (L > R; n = 3), and those witha higher number in the right versus the left hemisphere(R > L; n = 5; Table 1).

2.2. Lesion analysis

The brain lesions of the patients were demonstrated bystructural MRI (Fig. 1). Anatomical 3D data sets were

1 In the paper by Burgel and coworkers (Burgel et al, 2006), alldescending projections originating from primary motor cortex (M1) wereidentified as ‘‘cortico-spinal” projections. This nomenclature is somewhatmisleading, since the approach these authors used also labelled motorprojections from the M1 face representation (K. Amunts, personalcommunication). Since these fibers do not project to the spinal cord, butto the facial nerve nuclei, we used the term ‘‘cortico-spinal/cortico-nucleartract” to refer to this structure.

M. Staudt et al. / Brain & Language 106 (2008) 177–183 179

obtained on a 1.5 Tesla Siemens Vision system (MPRAGE,128 contiguous sagittal slices, TR [repetitiontime] = 9.7 ms, TI [inversion time] = 300 ms, TE [echotime] = 4 ms, voxel size 1 � 1 � 1.5 mm3.) Mapping oflesions was carried out by one experimenter withoutknowledge of test results and clinical features of thepatients. The boundary of the lesion (including periventric-ular white matter loss and ventricular enlargement) wasdelineated manually on every single transversal slice ofthe individual MRI using MRIcro software (Rorden &Brett, 2000) (http://www.mricro.com). Periventricularwhite matter loss was determined by delineating theenlarged portion of the left ventricle through direct com-parison with the unaffected right ventricle shape on thesame transversal slice. Both the scan and lesion shape werethen transformed into stereotaxic space using the spatialnormalisation algorithm provided by SPM2 (http://www.fil.ion.ucl.ac.uk/spm/), using default settings. Fordetermination of the transformation parameters, cost-func-tion masking was employed (Brett, Leff, Rorden, & Ash-burner, 2001). None of the patients showed a midlineshift, neither before nor after normalisation (Fig. 1).

To investigate whether topographically different por-tions of a periventricular lesion are responsible for a dis-ruption of cortico-spinal hand motor projections and forthe reorganization of language into the contra-lesionalright hemisphere, we classified the patients into differentgroups and performed group contrasts using lesion sub-traction analysis (Rorden & Karnath, 2004). To identifythe white matter structures that are commonly damagedin patients who develop language representation predomi-nantly in the right hemisphere but are typically spared inthose with language representation predominantly in theleft hemisphere, a first contrast was performed. We sub-tracted the superimposed lesions of those patients with pre-dominant left hemisphere language representation (L > R)(Fig. 2A, 2nd row) from the overlap images of those withpredominant language representation in the right hemi-sphere (R > L) (Fig. 2A, 1st row). Moreover, to identifythe white matter structures that are commonly damagedin patients with disrupted crossed cortico-spinal projec-tions to the paretic hand but are typically spared in patientswith preserved hand motor projections, in a second con-trast we subtracted the patients with preserved cortico-spinal hand motor projections Fig. 2A, 4th row) from thepatients with disrupted cortico-spinal projections Fig. 2A,3rd row). For both contrasts, an arbitrarily chosen thresh-old of 70% difference between groups was applied to definevoxels that are ‘‘critically involved”, so that all voxels weremarked with

Number of patients in Group A with voxel lesioned

Total number of patients in Group A

�Number of patients in Group B with voxel lesioned

Total number of patients in Group B

> 70%

with Groups A and B being either patients with disrupted(A) versus preserved (B) hand motor projections, or withpredominantly right-hemispheric (A) versus predominantlyleft-hemispheric (B) language activation.

In our sample, this meant that, for the language con-trast, all voxels were marked in which a lesion was presentin 4/5 (80%) or 5/5 (100%) patients with right-hemisphericlanguage organization (Group A), but in 0/3 (0%) of thepatients with predominantly left-hemispheric languageactivation (Group B)—resulting in supra-threshold differ-ences of (80% � 0% = 80%) or (100% � 0% = 100%),respectively. For the hand motor contrast, all voxels weremarked in which a lesion was present in 3/3 patients(100%) with disrupted hand motor projections (GroupA0), but in 0/4 (0%) or only 1/4 patients (25%) with pre-served hand motor projections (Group B0)—resulting insupra-threshold differences of (100% � 0% = 100%) or(100% � 25% = 75%), respectively (Fig. 2B).

To identify the anatomical relation of the affected whitematter structures to the anatomical position of cortico-spinal/cortico-nuclear projections1 originating in the pri-mary motor cortex, we here used the new strategy of lesionanalysis suggested by Papageorgiou and co-workers (inpress). These authors combined established lesion subtrac-tion techniques with the stereotaxic probabilistic cytoarchi-tectonic atlas, the latter developed by the Julich group(Amunts & Zilles, 2001). In Fig. 3, we thus plotted theresulting subtraction images onto the stereotaxic probabi-listic cytoarchitectonic map of the cortico-spinal/cortico-nuclear tract by Burgel et al. (2006). This map illustratesthe relative frequency with which the cortico-spinal/cor-tico-nuclear tract of ten normal human brains was presenton a MNI reference brain in a voxel (e.g., a 50% value ofthe cortico-spinal tract in a certain voxel of the referencebrain indicates that the fiber tract was present in that voxelin five out of ten brains). The probabilistic cytoarchitecton-ic map thus serves as a measure of intersubject variabilityfor each voxel of the reference space.

3. Results

We found the two centers of overlap in the white matterclose to the left ventricle and clearly separated (Fig. 2).Plotting these centers onto the Julich stereotaxic probabi-listic cytoarchitectonic map revealed that both centersclearly affected the cortico-spinal/cortico-nuclear projec-tion (Fig. 3). The area typically damaged in patients withdisrupted cortico-spinal projections to the paretic hand(red area in Fig. 2B; pink contour in Fig. 3) extended from

Fig. 1. Coronal reconstructions of the normalized 3D data sets depicting the extent of the lesion in each individual patient. MNI y-coordinates of thecoronal sections are given.

180 M. Staudt et al. / Brain & Language 106 (2008) 177–183

MNI coordinates (x, �21; y, �23; z, 31) over (x, �21; y,�20; z, 32) to (x, �20; y, �17; z, 35). In contrast, the white

matter structure that was commonly damaged in patientswho developed language representation predominantly in

Fig. 2. (A) Conventional lesion overlay plots based on normalized T1-weighted MR images for the four groups of patients represented from top to bottomas follows: language representation predominantly in the right hemisphere, language representation predominantly in the left hemisphere, disruptedcrossed cortico-spinal projections to the paretic hand, preserved cortico-spinal projections. The number of overlapping lesions is illustrated by differentcolours, coding increasing frequencies from violet (n = 1) to red (n = max). MNI y-coordinates of the coronal sections are given. L > R, languagerepresentation predominantly in the left hemisphere; R > L, language representation predominantly in the right hemisphere. Note that patient #4 couldonly be included in the analysis regarding language, but not regarding motor projections, since no TMS data could be obtained. (B) Overlay plots of thesubtracted superimposed lesions of (i) patients showing language representation predominantly in the right hemisphere minus patients with languagerepresentation predominantly in the left hemisphere as well as (ii) patients with disrupted crossed cortico-spinal projections to the paretic hand minuspatients with preserved cortico-spinal projections (for mathematical formula see Section 2). The differences between the respective groups in each voxel areindicated by colors: regions damaged at least 70% more frequently in patients who developed language representation in the right hemisphere are markedin dark green (80%) and light green (100%); regions damaged at least 70% more frequently in patients with a disruption of the cortico-spinal projections tothe paretic hand are marked in dark red (75%) and light red (100%).

M. Staudt et al. / Brain & Language 106 (2008) 177–183 181

the contralesional right hemisphere (green area in Fig. 2B;white contour in Fig. 3) was located more inferiorly (z-direction) and more anteriorly (y-direction). The areaextended from MNI coordinates (x, �18; y, �22; z, 21)

over (x, �17; y, �18; z, 21) and (x, �18; y, �13; z, 22) to(x, �8; y, �4; z, 16).

Neither of the reverse contrasts, i.e., the contrast search-ing for brain areas typically damaged in patients with

Fig. 3. Probabilistic cytoarchitectonic map of the cortico-spinal/cortico-nuclear tract by Burgel and co-workers (2006). The color bar indicates theabsolute frequency of voxels containing the cortico-spinal/cortico-nuclear tract from 1 (dark blue) individual brain to 10 (red, overlap of all ten[=Maximum] brains). The superimposed pink contour represents the center of the subtracted lesion overlap obtained in the present study for patients withdisrupted crossed projections to the paretic hand (see red area in Fig. 2B). The superimposed white contour represents the center of the subtracted lesionoverlap obtained in the present study for patients who developed language representation predominantly in the contralesional right hemisphere (see greenarea in Fig. 2B).

182 M. Staudt et al. / Brain & Language 106 (2008) 177–183

preserved cortico-spinal hand motor tracts but not inpatients with disrupted tracts, nor the contrast searchingfor brain areas typically damaged in patients with predom-inantly left-hemispheric language but not in patients withpredominantly right-hemispheric language yielded anyvoxels fulfilling this condition.

4. Discussion

Our present analysis revealed that topographically sepa-rate locations of early left periventricular brain lesions arecritical for the disruption of cortico-spinal hand motor pro-jections and for the induction of language reorganization inthe contralesional right hemisphere.

The congruency of the critical region for the integrity ordisruption of hand motor projections with cytoarchitecton-ical probabilistic maps of the cortico-spinal tract suggestthat the cortico-spinal system had already been establishedat the time of the insult (the early 3rd trimester of preg-nancy; Krageloh-Mann, 2004). This is consistent withobservations by Eyre and colleagues (2000), who reportedthat, in the human fetus, outgrowing cortico-spinal projec-tions have already reached their spinal target zones at thebeginning of the 3rd trimester of pregnancy. In contrast,in the somatosensory system, we could recently demon-strate that outgrowing thalamo-cortical somatosensoryprojections can bypass a periventricular lesion along alter-native routes, so that the new position of such pathways isno longer compatible with predictions from ‘‘adult” anat-omy (Staudt et al, 2006).

The white matter locus critically involved in inducingreorganization of language production in the contralesion-al right hemisphere is—at least partially—also located inthe course of motor projections originating in the primary

motor cortex, as determined from the present analysis com-bining lesion subtraction techniques with the Julich stereo-taxic probabilistic cytoarchitectonic atlas. Furthermore,this region is located anterior and inferior to the regioncritically involved in the integrity or disruption of handmotor projections, which is compatible with the positionof facial motor projections relative to hand motor projec-tions in the periventricular white matter: According tothe homuncular organization of the primary motor cortex(Fig. 2b, left), the face is represented inferior and, due tothe oblique course of the precentral gyrus, also anteriorto the hand. In addition, in the somatotopic organizationof the internal capsule, the facial motor projections passthrough the genu and, thus, again anterior to the handmotor projections passing through the posterior limb.Together, these findings corroborate our previously pub-lished hypothesis (Staudt et al., 2001) that structural dam-age to facial motor projections plays an important role ininducing right-hemispheric language organization in suchpatients. This hypothesis is also in accordance with recentreports on a relevance of speech-related cortical motorareas already during the early phases of normal languagedevelopment during the first year of life (Imada et al, 2006).

One could further confirm this finding by testing theintegrity or disruption of facial motor tracts in suchpatients using TMS. We refrained, however, from perform-ing such measurements in our patients, since TMS of theface motor region often implies painful stimulation of tem-poral muscles. Future research on periventricular lesionsmight also include diffusion tensor imaging, to furtherenhance our understanding of the functional consequencesof such lesions on specific white matter tracts.

The observations of this study should not be mistaken asclaiming that damage to facial motor projections is the

M. Staudt et al. / Brain & Language 106 (2008) 177–183 183

only possible mechanism responsible for right-hemisphericorganization of language in patients with left-sided peri-ventricular lesions. Especially in the patients with largerlesions, it is quite evident that other white matter structuresinvolved in language processing (e.g., the arcuate fascicu-lus) as well as subcortical grey matter structures such asthe basal ganglia are at least partially damaged; further-more, the periventricular lesions might also have had a neg-ative influence on the microanatomical integrity of corticallanguage areas, even if this was not evident on structuralMRI. Finally, all our patients were left-handed (most likelydue to their right-sided hemiparesis), so that a potentialinfluence of this ‘‘pathological left-handedness” on theorganization of language cannot be excluded either.

In conclusion, this study demonstrates that differentfunctional consequences of early periventricular brainlesions can be attributed to topographically distinct lociof the white matter damage.

Acknowledgments

This work was supported by the Deutsche Forschungs-gemeinschaft (SFB 550 - A4, C4, C5) and the EuropeanUnion (PERACT- Marie Curie Early Stage TrainingMEST-CT-2004-504321).

References

Amunts, K., & Zilles, K. (2001). Advances in cytoarchitectonic mappingof the human cerebral cortex. Neuroimaging Clinics of North America,

11, 151–169.Ashwal, S., Russman, B. S., Blasco, B. A., Miller, G., Sandler, A., Shevell,

M., et al. (2004). Practice parameter: Diagnostic assessment of thechild with cerebral palsy. Neurology, 62, 851–863.

Banker, B. Q., & Larroche, J. C. (1962). Periventricular leukomalacia ofinfancy. Archives of Neurology, 7, 386–410.

Brett, M., Leff, A. P., Rorden, C., & Ashburner, J. (2001). Spatialnormalization of brain images with focal lesions using cost functionmasking. NeuroImage, 14, 486–500.

Burgel, U., Amunts, K., Hoemke, L., Mohlberg, H., Gilsbach, J. M., &Zilles, K. (2006). White matter fiber tracts of the human brain: Three-dimensional mapping at microscopic resolution, topography andintersubject variability. NeuroImage, 29, 1092–1105.

Carr, L. J., Harrison, L. M., Evans, A. L., & Stephens, J. A. (1993).Patterns of central motor reorganization in hemiplegic cerebral palsy.Brain, 116, 1223–1247.

Eyre, J. A., Miller, S., Clowry, G. J., Conway, E. A., & Watts, C. (2000).Functional corticospinal projections are established prenatally in the

human foetus permitting involvement in the development of spinalmotor centres. Brain, 123, 51–64.

Imada, T., Zhang, Y., Cheour, M., Taulu, S., Ahonen, A., & Kuhl, P. K.(2006). Infant speech perception activates Broca’s area: A develop-mental magnetoencephalography study. Neuroreport, 17, 957–962.

Krageloh-Mann, I. (2004). Imaging of early brain injury and corticalplasticity. Experimental Neurology, 190, S84–S90.

Lidzba, K., Staudt, M., Wilke, M., & Krageloh-Mann, I. (2006).Visuospatial deficits in patients with early left-hemispheric lesionsand functional reorganization of language: Consequence of lesion orreorganization? Neuropsychologia, 44, 1088–1094.

Maegaki, Y., Maeoka, Y., Ishii, S., Shiota, M., Takeuchi, A., Yoshino,K., et al. (1997). Mechanisms of central motor reorganization inpediatric hemiplegic patients. Neuropediatrics, 28, 168–174.

Muter, V., Taylor, S., & Vargha-Khadem, F. (1997). A longitudinal studyof early intellectual development in hemiplegic children. Neuropsych-

ologia, 35, 289–298.Nezu, A., Kimura, S., Takeshita, S., & Tanaka, M. (1999). Functional

recovery in hemiplegic cerebral palsy: Ipsilateral electromyographicresponses to focal transcranial magnetic stimulation. Brain and

Development, 21, 162–165.Papageorgiou, E., Ticini, L. F., Hardiess, G., Schaeffel, F., Wiethoelter,

H., Mallot, H., Bahlo, S., Wilhelm, B., Vonthein, R., Schiefer, U., &Karnath, H. O. (in press). Anatomy of the pupillary light reflexpathway: cytoarchitectonic probabilistic maps in hemianopic patients.Neurology.

Rorden, C., & Brett, M. (2000). Stereotaxic display of brain lesions.Behavioral Neurology, 12, 191–200.

Rorden, C., & Karnath, H.-O. (2004). Using human brain lesions to inferfunction: a relic from a past era in the fMRI age? Nature Reviews

Neuroscience, 5, 813–819.Staudt, M., Braun, C., Gerloff, C., Erb, M., Grodd, W., & Krageloh-

Mann, I. (2006). Developing somatosensory projections bypass peri-ventricular brain lesions. Neurology, 67, 522–525.

Staudt, M., Gerloff, C., Grodd, W., Holthausen, H., Niemann, G., &Krageloh-Mann, I. (2004). Reorganization in congenital hemiparesisacquired at different gestational ages. Annals of Neurology, 56,854–863.

Staudt, M., Grodd, W., Gerloff, C., Erb, M., Stitz, J., & Krageloh-Mann,I. (2002a). Two types of ipsilateral reorganization in congenitalhemiparesis: A TMS and fMRI study. Brain, 125, 2222–2237.

Staudt, M., Grodd, W., Niemann, G., Wildgruber, D., Erb, M., &Krageloh-Mann, I. (2001). Early left periventricular brain lesionsinduce right hemispheric organization of speech. Neurology, 57,122–125.

Staudt, M., Lidzba, K., Grodd, W., Wildgruber, D., Erb, M., & Krageloh-Mann, I. (2002b). Right hemispheric organization of languagefollowing early left-sided brain lesions: Functional MRI topography.NeuroImage, 16, 954–967.

Tewes, U. (1994). Hamburg-Wechsler Intelligenztest fur Erwachsene.Revision 1991 (2nd ed.). Huber, Bern.

Wildgruber, D., Ackermann, H., Klose, U., Kardatzki, B., & Grodd, W.(1996). Functional lateralization of speech production at primarymotor cortex: A fMRI study. Neuroreport, 7, 2791–2795.