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Pathogenesis of subcortical visuo-spatial neglect. A HMPAO SPECT study
\
Pergamon
PII] S9917Ð2821"85#99015Ð0
Neuropsycholo`ia\ Vol[ 24\ No[ 4\ pp[ 620Ð624\ 0886 Þ 0886 Elsevier Science Ltd[ All rights reserved Printed in Great Britain 9917Ð2821:86 ,06[99¦9[99
Pathogenesis of subcortical visuo!spatial neglect[ A HMPAO SPECT study GUY DEMEURISSE\ & CLAUDE HUBLET\ JACQUES PATERNOT\$ CATHERINE COLSON and WILLY SERNICLAES% Service de Revalidation Neurologique\ CHU Brugmann\ Brussels\ Belgium^ $Service de Diagnostic par Radio!Isotopes\ CHU Brugmann\ Brussels\ Belgium^ %Laboratoire de Statistiques Medicales\ Ecole de Sante Publique\ ULB\ Brussels\ Belgium "Received 2 June 0885^ accepted 15 October 0885#
Abstract*The pathophysiology of neuropsychological disorders due to right deep!seated hemispheric lesions remains a debated point[ We undertook this study to check the hypothesis according to which remote cortical dysfunction could be responsible for the occurrence of neglect[ Twenty!eight patients presenting with a right!sided subcortical stroke were studied[ A neuropsychological battery of tests suitable for assessment of possible visuo!spatial neglect was performed as well as HMPAO SPECT[ Neglect was observed in 04 cases out of 17[ The lesion|s site "at CT and:or MRI# did not allow discrimination between patients without neglect and patients with neglect[ The latter however could be distinguished from the former by the presence of a remote decrease in cortical blood ~ow in the right temporo!parietal region[ By suggesting that cortical involvement is necessary for the occurrence of neglect\ the results were interpreted according to a network approach in which subcortical neglect is attributed to a cortical deprivation from a}erent input in the posterior part of the brain[ Þ 0886 Elsevier Science Ltd[ Key Words] diaschisis^ neglect^ stroke^ subcortical lesion^ cerebral blood ~ow[
two patients with infarction in the right anterior cho! roidal artery territory\ neglect was directly assigned to cortical diaschisis ð3Ł[ In a case with a right cap! sulolenticular hematoma\ a cortical hypometabolism was observed in areas belonging to networks involved in spa! tial representation ð19Ł[ In a recent study ð4Ł\ a regional cortical CBF reduction was observed in two patients with a right deep!seated white matter infarct[ In the patient with neglect "case nr[ 3#\ temporo!parietal areas were concerned whereas in the patient without neglect "case nr[ 4#\ the low ~ow area was situated more anteriorly[ Results obtained in a preliminary study bearing on a limited sample of patients with right deep!seated lesions studied with 1d[xenon 022 inhalation method and single photon emission CT "SPECT# using 88 m Tc!hexamethyl propylene amine oxime "HMPAO#\ suggested that dys! function in the right inferior parietal region could play a crucial role in the occurrence of neglect ð04Ł[ However\ neglect could be present without asymmetry in cortical cerebral perfusion and severe cortical hypoperfusion could also be present without hemispatial neglect ð09Ł[ The question of whether neglect is related or not to the presence of cortical dysfunction thus remains contro! versial[
Introduction The pathophysiology of neuropsychological disorders due to deep!seated hemispheric lesions remains a debated point[ Actually\ the neural mechanism most frequently evoked suggests a causal relationship between a remote cortical decrease in neuronal activity "akin to diaschisis# and the occurrence of neuropsychological disorders[ However\ till now\ most studies were devoted to left! sided lesions and language disorders[ In some other works\ patients with left and right lesions were pooled and a separate analysis of the cortical remote e}ects according to the lesion|s lateralization was not possible ð2\ 07\ 08\ 15Ł[ Studies speci_cally devoted to right!sided lesions and subcortical neglect are scarce[ In a study by Baron et al[ ð1Ł bearing on thalamic strokes\ four right! sided lesions were observed^ di}use cortical hypo! metabolism was signi_cant in three patients with neglect and absent in the patient without neglect[ In a study of &Address for correspondence] G[ Demeurisse\ Service de Revalidation Neurologique\ CHU Brugmann\ Place A[ Van Gehuchten\ 3!B!0919!Brussels\ Belgium^ fax] 21!1!2352557^ tel[] 21!1!3661338[
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G[ Demeurisse et al[:SPECT in subcortical neglect
The purpose of the present study was to investigate further the cortical remote e}ects in relation with possible neglect in a larger sample of patients with right!sided deep!seated hemispheric lesions[
Material and methods Twenty!eight stroke patients "06 males and 00 females# aged 40Ð77 years "mean 54 years# admitted to our department for stroke rehabilitation were selected according to the following criteria] , Right!handedness assessed by the Edinburgh inventory ð06Ł[ , No history of any previous neurological event[ , Absence of mental deterioration according to a standard neuropsychological investigation performed at the admission to our department and including the following tests] assess! ment of time and space orientation\ memory for con! temporary events\ auditoryÐverbal memory "Rey|s 04 words test#\ general intellectual abilities "verbal part of the WAIS or Standard Progressive Matrices of Raven#[ , Presence "at CT and:or MRI# of a single right!sided deep! seated vascular lesion sparing the cortex even at the depth of the sulci[ Lacunae were excluded[ After incorporation into the study\ possible visuo!spatial neg! lect was assessed with a more detailed neuropsychological bat! tery involving seven tests presented to the patients in the same order[ Letter cancellation task\ Copy of Rey|s _gure ð11Ł\ Albert|s cancellation task ð0Ł\ Spontaneous drawing of a wheel\ Zazzo|s cancellation task ð16Ł\ Line bisection task\ Reading of words in which the right part could be meaningful separately "ex[ toothbrush#[ Normative values were established previously in a population of 03 subjects ð04Ł[ For each cancellation task\ the scores were obtained by with! drawing the number of targets detected on the left side from the number of targets detected on the right side[ For the line bisection task "099 mm length#\ the score was the number of millimeters deviation from the true center of the line\ a positive score corresponding to a deviation towards the right[ For these tests\ any positive score −1[4 S[D[ above the mean normal value was considered as pathological[ Three independent examiners assessed the presence of neglect in the drawings[ In the reading task\ the control subjects had an errorless performance^ consequently\ any omission of the left part of a word was abnormal[ The severity of neglect was assessed according to the number of tests displaying signs of neglect[ On the basis of the results at the neglect battery\ our patient population was divided into three subgroups] patients without neglect\ with moderate neg! lect "¾2 pathological tests#\ and with severe neglect "×2 patho! logical tests#[ CT scans were performed without enhancement[ Sixteen con! tiguous planes "7 mm thick# parallel to the orbito!meatal line were obtained[ Lesions on each CT slice were projected on standard templates "from Shipps et al[ ð13Ł and Duvernoy|s atlas ð7Ł#[ The approximate size of the lesions was estimated by summing up the surfaces of the lesions measured with a planimeter in the di}erent CT slices[
MRI\ performed in seven cases\ did not show additional cortical lesions[ Cerebral blood ~ows "CBF# were explored by 88 m Tc HMPAO SPECT "SOPHA DS X gamma!camera#[ The head of the patient was _xed using an adjustable cu} so that the transversal slices were parallel to the canthomeatal line[ 88 m Tc Pertechnetate was mixed in our laboratory with HMPAO "Exametazine# according to the procedure provided by Amer! sham "UK#[ The gamma!camera was set on the 88 m Tc peak "19) symmetrical#[ A bolus containing 639 MBq "19 mCi# 88 m Tc HMPAO was injected intravenously within 04 min after reconstitution[ Recordings were started about 04 min later on 53 angular projections "matrix format 53×53 pixels# obtained during a 05 min complete rotation time of the camera^ in such conditions\ each projection involved 29 999 to 49 999 counts[ A set of transversal "2[34 mm thick#\ coronal and sagittal slices was obtained by a standard _ltered back!projection recon! struction method using a classical HammingÐHann _lter[ In order to investigate certain regions\ transversal slices were summed up to form three 02\7 mm thick slices "Fig[ 0#[ Within these slices\ regions of interest "ROI# were de_ned back to the postcentral gyrus and in front of the precentral gyrus in order to investigate superior and inferior parietal areas\ the posterior temporal region and premotor frontal areas[ These ROI were selected because in neural models of spatial attention\ both premotor frontal and parieto!temporal regions might be involved[ "for a review\ see ð5Ł#[ The antero!posterior local! ization of the central gyrus was obtained using anatomical atlas ð7\ 13Ł[ Within each ROI\ the three highest values of activity "ex! pressed as counts per min per pixel# were summed up and con! sidered as an accurate estimation of cortical CBF[ However\ data provided by SPECT using HMPAO are semi!quantitative[ Therefore\ indexes of right to left asymmetry "asymmetry indexes] AI# were further established as ratios between activities in right and left homologous cortical ROI "AI 0] superior par! ietal area\ AI 1] inferior parietal area\ AI 2] posterior temporal region\ AI 3ÐAI 4] frontal areas#[ During the recordings\ the subjects were lying in a quiet dimly lit room with eyes closed and ears unplugged[ The neglect battery was performed about 28 days after onset and SPECT about 30 days "14Ð45# after stroke[ CT scans were performed on average 06 days after onset[ ANOVAs were used in order to assess the relationships between clinical and SPECT data[
Fig[ 0[ Localization of the regions of interest] 0] 1] 2] 3Ð4]
superior parietal area[ inferior parietal area[ posterior temporal region[ prefrontal areas[
G[ Demeurisse et al[:SPECT in subcortical neglect
Results Clinical and radiological data are represented in Table 0[ Neglect was observed in 04 cases out of 17[ Neglect was moderate in nine cases and severe in six cases[ Ischemic lesions were observed in 12 patients and hem! atomas in _ve patients[ Whether neglect was present or not\ the most frequently deep!seated injured structures were the lenticular nucleus and white matter tracts "cen! trum semiovale and posterior limb of the internal capsule# "Table 0#[ Deep!seated grey nuclei "lenticular nucleus\ thalamus# were injured more frequently in neglect pat! ients "03:04Ð82)# as compared to patients without neg! lect "8:02Ð58)#[ However\ this is hardly a trend "P 9[138#^ basically\ the lesion|s site did not allow to discriminate patients with neglect from patients without neglect[ However\ as a rule\ the size of the lesions was greater "approximately 29) larger# in neglect patients as com! pared to patients without neglect\ but there were also neglect patients with rather small lesions and the di}er! ences between subgroups did not reach a signi_cance
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level[ All neglect patients had a reduction in right cortical CBF[ Table 1 gives the mean values\ standard deviations and medians of the _ve right to left CBF asymmetry Table 1[ Means "2S[D[# and medians of the _ve perfusion asymmetry indexes "AI# in three clinical categories Without neglect Moderate neglect Severe neglect AI 0 M2S[D[ median AI 1 M2S[D[ median AI 2 M2S[D[ median AI 3 M2S[D[ median AI 4 M2S[D[ median
86[222[0 86[2
80[627[3 83[6
77[421[7 76[3
86[626[1 86[4
78[724[7 77[7
75[323[4 76[7
88[123[0 88[6
76[624[0 76[4
75[824[7 76[5
87[626[8 88[8
83[826[9 83[1
85[022[2 85[7
88[322[2 099[7
83[323[6 82[5
82[923[2 82[2
Table 0[ Clinical and radiological data Patient N>
Sex
Age
ACT
LCT
ZCT
0 1 2 3 4 5 6 7 8 09 00 01 02
F F M M M M M F F M M M M
60 53 58 47 51 53 53 72 56 53 77 56 48
9 9 9 9 9 9 9 9 9 9 9 0 9
9 0 9 9 9 9 9 9 0 9 0 0 0
9 9 9 9 9 −0 0 9 9 9 −0 0 0
03 04 05 06 07 08 19 10 11
M M M M M F M F F
54 43 40 46 50 61 51 69 57
9 9 9 9 9 9 8 2 2
2 3 3 0 3 2 7 1 2
12 13 14 15 16 17
M M F F F F
48 53 72 43 43 68
−2 12 16 9 0 03
6 2 00 4 3 2
LBT
CRF
SDW
RW
Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð
Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð
Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð
2 0 3 9 2 1 3 2 9
Moderate neglect 0\4 Ð 9\6 Ð 4\4 Ð 1 ¦ 2 ¦ 2 ¦ 1\6 Ð −3 ¦ 9 U
Ð Ð Ð Ð Ð Ð Ð Ð Ð
Ð Ð Ð Ð Ð Ð Ð Ð Ð
¦ ¦
00 09 U U 4 4
Severe neglect 26 ¦ 9\1 ¦ 14\4 U −9\6 ¦ 09\1 ¦ 9\4 ¦
Ð ¦ ¦ ¦ ¦ ¦
¦ Ð ¦ ¦ ¦ Ð
¦ ¦
No neglect 3\4 9\0 9\5 −0 9\2 9\6 1\2 2\5 0\1 1\7 9 9 9
PLIC
LN
CN
Th
¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦
¦ ¦ ¦ ¦ ¦
¦ ¦
¦ ¦ ¦ ¦
¦ ¦ ¦
¦ ¦ ¦ ¦ ¦ ¦
¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦
CSO
¦ ¦ ¦ ¦
¦ ¦
¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦
¦
¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦
ACT Albert cancellation task^ LCT letter cancellation task^ ZCT Zazzo cancellation task^ LBT line bisection task^ CRF copy of Rey|s _gure^ SDW spontaneous drawing of a wheel^ RW reading of words[ Pathological results are underlined^ U unrealizable[ PLIC posterior limb of internal capsule^ LN lenticular nucleus^ CN caudate nucleus^ Th thalamus^ CSO centrum semiovale[
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G[ Demeurisse et al[:SPECT in subcortical neglect
indexes "AI# for the three clinical categories[ Di}erences between the di}erent clinical categories were larger for AI 0\ AI 1 and AI 2 than for AI 3 and AI 4[ Variable AI 2 exhibited the largest di}erence[ This was also true for median values[ ANOVAs in which AI was taken as a single dependent variable were performed[ Three di}erent factors were considered] neglect "2 levels#\ site "4 levels# and subject[ The latter was treated as a random factor nested in neglect category\ with 02\ 8 and 5 levels respectively for absence of neglect\ moderate and severe neglect[ E}ect of neglect was highly signi_cant ðF"1\14# 05[91^ P ³ 9[994Ł[ E}ect of site was also highly signi_cant ðF"3\099# 3[56^ P ³ 9[994Ł[ The interaction was how! ever just non!signi_cant ðF"7\099# 0[73^ P 9[967Ł[ The fact that the interaction was not signi_cant might suggest that the magnitude of AI di}erences between subgroups did not depend on site[ However\ the inter! action was not far from signi_cance[ Given that sample sizes were fairly small\ the e}ect might reveal itself with slightly larger samples[ Further analyses were performed by taking only two categories for performing the ANOVAs\ namely absence of neglect vs presence of neglect[ The latter category included both subjects with mod! erate neglect and those with severe neglect[ This is sound and has the advantage of increasing sample size and hence the power of the tests[ E}ect of neglect was again highly signi_cant ðF"0\15# 20[57^ P ³ 9[994#[ E}ect of site also remained highly signi_cant ðF"3\093# 3[65^ P ³ 9[994Ł and the interaction became signi_cant ðF"3\093# 12[12^ P 9[904Ł[ This means that e}ect of presence vs absence of neglect on AI depends on site[ Contrasts between neglect e}ects for each pair of sites were also calculated[ Table 2 gives the corresponding F values for the 09 possible site pairs[ Di}erences between AI 3 and AI 2\ AI 3 and AI 1\ and AI 4 and AI 2 were signi_cant without Bonferroni correction[ Only the di}erence between AI 3 and AI 2 remained signi_cant with Bonferroni correction[ This means that interaction between neglect and site is mainly due to the magnitude of the e}ect of neglect between sites 3 and 2 "see Table 1#[ The neglect:site inter! action might also be due to di}erences between sites 3 and 1\ and between 4 and 2[ However\ these di}erences are at the limit of statistical signi_cance[ Table 2[ F values for contrasts between each pair of sites
AI 1 AI 2 AI 3 AI 4
AI 0
AI 1
AI 2
AI 3
9[71 2[54 0[89 9[15
0[90 4[10 1[99
09[72 4[76
9[64
P³9[94 without Bonferroni correction[ P³9[94 with Bonferroni correction[
Discussion In the present study\ neglect was observed in 43) of our cases[ In other studies devoted to subcortical neglect\ the frequencies of occurrence of neglect varied from 14) to 60) ð00\ 04\ 14Ł\ most probably because neuro! psychological batteries of tests of di}erent complexity were used to assess the presence of neglect[ Six patients only presented with severe neglect[ But*in the present study*no patient had a lesion centered on and restricted to the sole thalamus[ Now\ the severity of neglect would be more important in thalamic and cortical lesions ð5\ 14Ł whereas in deep!seated lesions not involving the thala! mus\ the disorder would be rather mild ð5Ł[ Additional cortical damage not seen on CT has already been observed in patients with lenticulostriate infarcts ð01Ł^ such was not the case in our patients assessed with both CT and MRI[ Regarding CT or MRI data\ our observations are in accordance with other previous studies ð00\ 14Ł[ As a rule\ in capsulo!lenticular lesions\ there is no speci_c structure whose injury proved to be necessary and su.cient to provoke neglect[ The analysis of morphological data thus contributes little to the comprehension of the patho! physiology of neglect[ Now\ in deep!seated lesions\ a remote reduction in cortical cerebral blood ~ow or metabolism has been repeatedly observed[ Controversial interpretations regarding the pathophysiology of this phenomenon have been proposed "for a review\ see ð5Ł and ð8Ł#^ but\ the most generally accepted hypothesis ascribed the cortical dysfunction to a disconnection within a neural network leading to a deprivation from a}erent input to the cortex akin to diaschisis[ An additional step was to assume that these remote e}ects could play a role in the patho! physiology of the behavioral disorder[ Till now\ literature data concerned most often left!sided lesions and language disorders[ As stated in the introduction section\ results concerning right!sided lesions and neglect are not con! clusive[ In the present study\ neglect patients could be distinguished from patients without neglect by the pres! ence of a remote decrease in cortical cerebral blood ~ow in the right temporo!parietal region[ This reduction in CBF was slightly more pronounced in patients with sev! ere neglect as compared to the other neglect patients\ the observed di}erences being however not signi_cant[ According to a network approach\ neuropsychological functions are subserved by various cerebral regions including cortical areas\ subcortical grey nuclei and their reciprocal connections[ Disruption of deep!seated neural connections would lead to a remote cortical deprivation from a}erent input[ By assigning a crucial role in spatial attention disorder to a right cortical parieto!temporal dysfunction\ our results suggest that cortical involvement is necessary for the occurrence of cognitive disorders[ Such observation is in accordance with anatomo!clinical studies in which the most frequent correlate of neglect is with cortical retro!rolandic temporo!parietal lesions ð02\
G[ Demeurisse et al[:SPECT in subcortical neglect
14Ł[ Morphological lesions or dysfunction in the same speci_c areas are thus likely to provoke the same clinical syndrome[ Di}erent neural models regarding the modulation of directed spatial attention have been evoked ð6\ 03\ 05\ 10\ 12Ł[ As a rule\ these models pointed out several cortical regions\ i[e[ premotor frontal and parieto!temporal areas[ Our results*showing a temporo!parietal cortical dys! function in neglect patients*are in accordance with these models and stress also the relevant role of posterior regions[ References 0[ Albert\ M[ L[ A simple test of visual neglect[ Neur! olo`y 12\ 547Ð553\ 0862[ 1[ Baron\ J[ C[\ D|Antona\ R[\ Pantano\ P[\ Serdaru\ M[\ Samson\ Y[ and Bousser\ M[ G[ E}ects of thal! amic stroke on energy metabolism of the cerebral cortex[ Brain 098\ 0132Ð0148\ 0875[ 2[ Baron\ J[ C[\ Levasseur\ M[\ Mazoyer\ B[\ Legault! Demare\ F[\ Mauguiere\ F[\ Pappata\ S[\ Jedynak\ P[\ Derome\ P[\ Cambier\ J[\ Tran!Dihn\ S[ and Cambon\ H[ Thalamocortical diaschisis] positron emission tomography in humans[ Journal of Neur! olo`y\ Neurosur`ery and Psychiatry 44\ 824Ð831\ 0881[ 3[ Bogousslavsky\ J[\ Miklossy\ J[\ Regli\ F[\ Deruaz\ J[ P[\ Assal\ G[ and Delaloye\ B[ Subcortical neglect] Neuropsychological\ SPECT\ and neuropathological correlations with anterior choroidal artery territory infarction[ Annals of Neurolo`y 12\ 337Ð341\ 0877[ 4[ Bradvik\ B[\ Sonesson\ B[\ Ryding\ E[ and Rosen\ I[ Spatial and perceptual impairment related to cortical cerebral blood ~ow and EEG in deep white matter infarcts of the right hemisphere[ European Neurolo`y 24\ 79Ð74\ 0884[ 5[ Cappa\ S[ F[ and Vallar\ G[ Neuropsychological dis! orders after subcortical lesions] Implications for neu! ral models of language and spatial attention[ In Neuropsycholo`ical Disorders Associated with Sub! cortical Lesions\ G[ Vallar\ S[ F[ Cappa and C[!W[ Wallesch "Editors#\ pp[ 6Ð30[ Oxford University Press\ Oxford\ 0881[ 6[ De Renzi\ E[\ Gentilini\ M[ and Barbieri\ C[ Auditory neglect[ Journal of Neurolo`y\ Neurosur`ery and Psy! chiatry 41\ 502Ð506\ 0878[ 7[ Duvernoy\ H[ Le cerveau humain[ Surface\ Coupes Seriees Tridimensionnelles et IRM[ Springer Verlag France\ Paris\ 0881[ 8[ Feeney\ D[ and Baron\ J[ C[ Diaschisis[ Stroke 06\ 706Ð729\ 0875[ 09[ Ferro\ J[\ Cantinho\ G[\ Levy\ A[ and Godinho\ F[ Subcortical neglect] is cortical diaschisis relevant< In Neuropsycholo`ical Disorders Associated with Sub! cortical Lesions\ G[ Vallar\ S[ F[ Cappa and C[!W[ Wallesch "Editors#\ pp[ 316Ð325[ Oxford University Press\ Oxford\ 0881[ 00[ Ferro\ J[ M[\ Kertesz\ A[ and Black\ S[ E[ Subcortical neglect] Quantitation\ anatomy and recovery[ Neur! olo`y 26\ 0376Ð0381\ 0876[
624
01[ Godefroy\ O[\ Rousseaux\ M[\ Leys\ D[\ Destee\ A[\ Scheltens\ P[ and Pruvo\ J[ P[ Frontal lobe dys! function in unilateral lenticulostriate infarcts[ Archives of Neurolo`y 38\ 0174Ð0178\ 0881[ 02[ Heilman\ K[\ Valenstein\ E[ and Watson\ R[ Local! ization of neglect[ In Localization in Neuro! psycholo`y\ Kertesz\ A[ "Editor#\ pp[ 360Ð381[ Aca! demic Press\ New York\ 0872[ 03[ Heilman\ K[\ Watson\ R[ and Valenstein\ E[ Neglect and Related Disorders[ In Clinical Neuropsycholo`y\ 1nd edn\ K[ Heilman and E[ Valenstein "Editors#\ pp[ 132Ð182[ Oxford University Press\ New York\ 0874[ 04[ Hublet\ C[\ Demeurisse\ G[\ Paternot\ J[\ Colson\ C[ and Capon\ A[ Remote cortical dysfunction as a possible cause of subcortical neglect< A regional cer! ebral blood ~ow study[ European Neurolo`y 24\ 143Ð 147\ 0884[ 05[ Mesulam\ M[!M[ A cortical network for directed attention and unilateral neglect[ Annals of Neurolo`y 09\ 298Ð214\ 0870[ 06[ Old_elds\ R[ The assessment and analysis of hand! edness] The Edinburgh inventory[ Neuropsycholo`ia 8\ 86Ð002\ 0860[ 07[ Pappata\ S[\ Mazoyer\ B[\ Tran!Dihn\ S[\ Cambon\ H[\ Levasseur\ M[ and Baron\ J[ C[ E}ects of cap! sular or thalamic stroke on metabolism in the cortex and cerebellum] A positron tomography study[ Stroke 10\ 408Ð413\ 0889[ 08[ Perani\ D[\ Vallar\ G[\ Cappa\ S[\ Messa\ C[ and Fazio\ F[ Aphasia and neglect after subcortical stroke] A clinical cerebral perfusion correlation study[ Brain 009\ 0100Ð0118\ 0876[ 19[ Perani\ D[\ Vallar\ G[\ Paulesu\ E[\ Alberoni\ M[ and Fazio\ F[ Left and right hemisphere contribution to recovery from neglect after right hemisphere dam! age*An "07F# FDG PET study of two cases[ Neuropsycholo`ia 20\ 004Ð014\ 0882[ 10[ Posner\ M[\ Petersen\ S[\ Fox\ P[ and Raichle\ M[ Localization of cognitive operations in the human brain[ Science 139\ 0516Ð0520\ 0877[ 11[ Rey\ A[ Test de copie d|une _`ure complexe[ Editions du Centre de Psychologie Appliquee\ Paris\ 0848[ 12[ Rizzolatti\ G[\ Gentilucci\ M[ and Mattelli\ M[ Selec! tive spatial attention] one center\ one circuit or many circuits< In Attention and Performance XI\ M[ Posner and O[ Marin "Editors#\ pp[ 140Ð154[ Lawrence Erlbaum\ Hillsdale\ NJ\ 0874[ 13[ Shipps\ F[\ Mc Andrew Jones\ J[ and D|Agostino\ A[ Atlas of Brain Anatomy for C[ T[ Scans[ Charles C[ Thomas\ Spring_eld\ 0866[ 14[ Vallar\ G[ and Perani\ D[ The anatomy of unilateral neglect after right hemisphere stroke lesions[ A clinical:CT scan correlation study in man[ Neuro! psycholo`ia 13\ 598Ð511\ 0875[ 15[ Vallar\ G[\ Perani\ D[\ Cappa\ S[\ Messa\ C[\ Lenzi\ G[ L[ and Fazio\ F[ Recovery from aphasia and neglect after subcortical stroke] neuropsychological and cerebral perfusion study[ Journal of Neurolo`y\ Neurosur`ery and Psychiatry 40\ 0158Ð0165\ 0877[ 16[ Zazzo\ R[ Le test des deux barrages[ Manuel pour l|examen psycholo`ique de l|enfant II\ Vol[ 6\ pp[ 369Ð 464[ Delachaux et Niestle\ Neufcha¼tel\ 0858[
Pergamon
PII] S9917Ð2821"85#99015Ð0
Neuropsycholo`ia\ Vol[ 24\ No[ 4\ pp[ 620Ð624\ 0886 Þ 0886 Elsevier Science Ltd[ All rights reserved Printed in Great Britain 9917Ð2821:86 ,06[99¦9[99
Pathogenesis of subcortical visuo!spatial neglect[ A HMPAO SPECT study GUY DEMEURISSE\ & CLAUDE HUBLET\ JACQUES PATERNOT\$ CATHERINE COLSON and WILLY SERNICLAES% Service de Revalidation Neurologique\ CHU Brugmann\ Brussels\ Belgium^ $Service de Diagnostic par Radio!Isotopes\ CHU Brugmann\ Brussels\ Belgium^ %Laboratoire de Statistiques Medicales\ Ecole de Sante Publique\ ULB\ Brussels\ Belgium "Received 2 June 0885^ accepted 15 October 0885#
Abstract*The pathophysiology of neuropsychological disorders due to right deep!seated hemispheric lesions remains a debated point[ We undertook this study to check the hypothesis according to which remote cortical dysfunction could be responsible for the occurrence of neglect[ Twenty!eight patients presenting with a right!sided subcortical stroke were studied[ A neuropsychological battery of tests suitable for assessment of possible visuo!spatial neglect was performed as well as HMPAO SPECT[ Neglect was observed in 04 cases out of 17[ The lesion|s site "at CT and:or MRI# did not allow discrimination between patients without neglect and patients with neglect[ The latter however could be distinguished from the former by the presence of a remote decrease in cortical blood ~ow in the right temporo!parietal region[ By suggesting that cortical involvement is necessary for the occurrence of neglect\ the results were interpreted according to a network approach in which subcortical neglect is attributed to a cortical deprivation from a}erent input in the posterior part of the brain[ Þ 0886 Elsevier Science Ltd[ Key Words] diaschisis^ neglect^ stroke^ subcortical lesion^ cerebral blood ~ow[
two patients with infarction in the right anterior cho! roidal artery territory\ neglect was directly assigned to cortical diaschisis ð3Ł[ In a case with a right cap! sulolenticular hematoma\ a cortical hypometabolism was observed in areas belonging to networks involved in spa! tial representation ð19Ł[ In a recent study ð4Ł\ a regional cortical CBF reduction was observed in two patients with a right deep!seated white matter infarct[ In the patient with neglect "case nr[ 3#\ temporo!parietal areas were concerned whereas in the patient without neglect "case nr[ 4#\ the low ~ow area was situated more anteriorly[ Results obtained in a preliminary study bearing on a limited sample of patients with right deep!seated lesions studied with 1d[xenon 022 inhalation method and single photon emission CT "SPECT# using 88 m Tc!hexamethyl propylene amine oxime "HMPAO#\ suggested that dys! function in the right inferior parietal region could play a crucial role in the occurrence of neglect ð04Ł[ However\ neglect could be present without asymmetry in cortical cerebral perfusion and severe cortical hypoperfusion could also be present without hemispatial neglect ð09Ł[ The question of whether neglect is related or not to the presence of cortical dysfunction thus remains contro! versial[
Introduction The pathophysiology of neuropsychological disorders due to deep!seated hemispheric lesions remains a debated point[ Actually\ the neural mechanism most frequently evoked suggests a causal relationship between a remote cortical decrease in neuronal activity "akin to diaschisis# and the occurrence of neuropsychological disorders[ However\ till now\ most studies were devoted to left! sided lesions and language disorders[ In some other works\ patients with left and right lesions were pooled and a separate analysis of the cortical remote e}ects according to the lesion|s lateralization was not possible ð2\ 07\ 08\ 15Ł[ Studies speci_cally devoted to right!sided lesions and subcortical neglect are scarce[ In a study by Baron et al[ ð1Ł bearing on thalamic strokes\ four right! sided lesions were observed^ di}use cortical hypo! metabolism was signi_cant in three patients with neglect and absent in the patient without neglect[ In a study of &Address for correspondence] G[ Demeurisse\ Service de Revalidation Neurologique\ CHU Brugmann\ Place A[ Van Gehuchten\ 3!B!0919!Brussels\ Belgium^ fax] 21!1!2352557^ tel[] 21!1!3661338[
620
621
G[ Demeurisse et al[:SPECT in subcortical neglect
The purpose of the present study was to investigate further the cortical remote e}ects in relation with possible neglect in a larger sample of patients with right!sided deep!seated hemispheric lesions[
Material and methods Twenty!eight stroke patients "06 males and 00 females# aged 40Ð77 years "mean 54 years# admitted to our department for stroke rehabilitation were selected according to the following criteria] , Right!handedness assessed by the Edinburgh inventory ð06Ł[ , No history of any previous neurological event[ , Absence of mental deterioration according to a standard neuropsychological investigation performed at the admission to our department and including the following tests] assess! ment of time and space orientation\ memory for con! temporary events\ auditoryÐverbal memory "Rey|s 04 words test#\ general intellectual abilities "verbal part of the WAIS or Standard Progressive Matrices of Raven#[ , Presence "at CT and:or MRI# of a single right!sided deep! seated vascular lesion sparing the cortex even at the depth of the sulci[ Lacunae were excluded[ After incorporation into the study\ possible visuo!spatial neg! lect was assessed with a more detailed neuropsychological bat! tery involving seven tests presented to the patients in the same order[ Letter cancellation task\ Copy of Rey|s _gure ð11Ł\ Albert|s cancellation task ð0Ł\ Spontaneous drawing of a wheel\ Zazzo|s cancellation task ð16Ł\ Line bisection task\ Reading of words in which the right part could be meaningful separately "ex[ toothbrush#[ Normative values were established previously in a population of 03 subjects ð04Ł[ For each cancellation task\ the scores were obtained by with! drawing the number of targets detected on the left side from the number of targets detected on the right side[ For the line bisection task "099 mm length#\ the score was the number of millimeters deviation from the true center of the line\ a positive score corresponding to a deviation towards the right[ For these tests\ any positive score −1[4 S[D[ above the mean normal value was considered as pathological[ Three independent examiners assessed the presence of neglect in the drawings[ In the reading task\ the control subjects had an errorless performance^ consequently\ any omission of the left part of a word was abnormal[ The severity of neglect was assessed according to the number of tests displaying signs of neglect[ On the basis of the results at the neglect battery\ our patient population was divided into three subgroups] patients without neglect\ with moderate neg! lect "¾2 pathological tests#\ and with severe neglect "×2 patho! logical tests#[ CT scans were performed without enhancement[ Sixteen con! tiguous planes "7 mm thick# parallel to the orbito!meatal line were obtained[ Lesions on each CT slice were projected on standard templates "from Shipps et al[ ð13Ł and Duvernoy|s atlas ð7Ł#[ The approximate size of the lesions was estimated by summing up the surfaces of the lesions measured with a planimeter in the di}erent CT slices[
MRI\ performed in seven cases\ did not show additional cortical lesions[ Cerebral blood ~ows "CBF# were explored by 88 m Tc HMPAO SPECT "SOPHA DS X gamma!camera#[ The head of the patient was _xed using an adjustable cu} so that the transversal slices were parallel to the canthomeatal line[ 88 m Tc Pertechnetate was mixed in our laboratory with HMPAO "Exametazine# according to the procedure provided by Amer! sham "UK#[ The gamma!camera was set on the 88 m Tc peak "19) symmetrical#[ A bolus containing 639 MBq "19 mCi# 88 m Tc HMPAO was injected intravenously within 04 min after reconstitution[ Recordings were started about 04 min later on 53 angular projections "matrix format 53×53 pixels# obtained during a 05 min complete rotation time of the camera^ in such conditions\ each projection involved 29 999 to 49 999 counts[ A set of transversal "2[34 mm thick#\ coronal and sagittal slices was obtained by a standard _ltered back!projection recon! struction method using a classical HammingÐHann _lter[ In order to investigate certain regions\ transversal slices were summed up to form three 02\7 mm thick slices "Fig[ 0#[ Within these slices\ regions of interest "ROI# were de_ned back to the postcentral gyrus and in front of the precentral gyrus in order to investigate superior and inferior parietal areas\ the posterior temporal region and premotor frontal areas[ These ROI were selected because in neural models of spatial attention\ both premotor frontal and parieto!temporal regions might be involved[ "for a review\ see ð5Ł#[ The antero!posterior local! ization of the central gyrus was obtained using anatomical atlas ð7\ 13Ł[ Within each ROI\ the three highest values of activity "ex! pressed as counts per min per pixel# were summed up and con! sidered as an accurate estimation of cortical CBF[ However\ data provided by SPECT using HMPAO are semi!quantitative[ Therefore\ indexes of right to left asymmetry "asymmetry indexes] AI# were further established as ratios between activities in right and left homologous cortical ROI "AI 0] superior par! ietal area\ AI 1] inferior parietal area\ AI 2] posterior temporal region\ AI 3ÐAI 4] frontal areas#[ During the recordings\ the subjects were lying in a quiet dimly lit room with eyes closed and ears unplugged[ The neglect battery was performed about 28 days after onset and SPECT about 30 days "14Ð45# after stroke[ CT scans were performed on average 06 days after onset[ ANOVAs were used in order to assess the relationships between clinical and SPECT data[
Fig[ 0[ Localization of the regions of interest] 0] 1] 2] 3Ð4]
superior parietal area[ inferior parietal area[ posterior temporal region[ prefrontal areas[
G[ Demeurisse et al[:SPECT in subcortical neglect
Results Clinical and radiological data are represented in Table 0[ Neglect was observed in 04 cases out of 17[ Neglect was moderate in nine cases and severe in six cases[ Ischemic lesions were observed in 12 patients and hem! atomas in _ve patients[ Whether neglect was present or not\ the most frequently deep!seated injured structures were the lenticular nucleus and white matter tracts "cen! trum semiovale and posterior limb of the internal capsule# "Table 0#[ Deep!seated grey nuclei "lenticular nucleus\ thalamus# were injured more frequently in neglect pat! ients "03:04Ð82)# as compared to patients without neg! lect "8:02Ð58)#[ However\ this is hardly a trend "P 9[138#^ basically\ the lesion|s site did not allow to discriminate patients with neglect from patients without neglect[ However\ as a rule\ the size of the lesions was greater "approximately 29) larger# in neglect patients as com! pared to patients without neglect\ but there were also neglect patients with rather small lesions and the di}er! ences between subgroups did not reach a signi_cance
622
level[ All neglect patients had a reduction in right cortical CBF[ Table 1 gives the mean values\ standard deviations and medians of the _ve right to left CBF asymmetry Table 1[ Means "2S[D[# and medians of the _ve perfusion asymmetry indexes "AI# in three clinical categories Without neglect Moderate neglect Severe neglect AI 0 M2S[D[ median AI 1 M2S[D[ median AI 2 M2S[D[ median AI 3 M2S[D[ median AI 4 M2S[D[ median
86[222[0 86[2
80[627[3 83[6
77[421[7 76[3
86[626[1 86[4
78[724[7 77[7
75[323[4 76[7
88[123[0 88[6
76[624[0 76[4
75[824[7 76[5
87[626[8 88[8
83[826[9 83[1
85[022[2 85[7
88[322[2 099[7
83[323[6 82[5
82[923[2 82[2
Table 0[ Clinical and radiological data Patient N>
Sex
Age
ACT
LCT
ZCT
0 1 2 3 4 5 6 7 8 09 00 01 02
F F M M M M M F F M M M M
60 53 58 47 51 53 53 72 56 53 77 56 48
9 9 9 9 9 9 9 9 9 9 9 0 9
9 0 9 9 9 9 9 9 0 9 0 0 0
9 9 9 9 9 −0 0 9 9 9 −0 0 0
03 04 05 06 07 08 19 10 11
M M M M M F M F F
54 43 40 46 50 61 51 69 57
9 9 9 9 9 9 8 2 2
2 3 3 0 3 2 7 1 2
12 13 14 15 16 17
M M F F F F
48 53 72 43 43 68
−2 12 16 9 0 03
6 2 00 4 3 2
LBT
CRF
SDW
RW
Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð
Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð
Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð Ð
2 0 3 9 2 1 3 2 9
Moderate neglect 0\4 Ð 9\6 Ð 4\4 Ð 1 ¦ 2 ¦ 2 ¦ 1\6 Ð −3 ¦ 9 U
Ð Ð Ð Ð Ð Ð Ð Ð Ð
Ð Ð Ð Ð Ð Ð Ð Ð Ð
¦ ¦
00 09 U U 4 4
Severe neglect 26 ¦ 9\1 ¦ 14\4 U −9\6 ¦ 09\1 ¦ 9\4 ¦
Ð ¦ ¦ ¦ ¦ ¦
¦ Ð ¦ ¦ ¦ Ð
¦ ¦
No neglect 3\4 9\0 9\5 −0 9\2 9\6 1\2 2\5 0\1 1\7 9 9 9
PLIC
LN
CN
Th
¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦
¦ ¦ ¦ ¦ ¦
¦ ¦
¦ ¦ ¦ ¦
¦ ¦ ¦
¦ ¦ ¦ ¦ ¦ ¦
¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦
CSO
¦ ¦ ¦ ¦
¦ ¦
¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦
¦
¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦ ¦
ACT Albert cancellation task^ LCT letter cancellation task^ ZCT Zazzo cancellation task^ LBT line bisection task^ CRF copy of Rey|s _gure^ SDW spontaneous drawing of a wheel^ RW reading of words[ Pathological results are underlined^ U unrealizable[ PLIC posterior limb of internal capsule^ LN lenticular nucleus^ CN caudate nucleus^ Th thalamus^ CSO centrum semiovale[
623
G[ Demeurisse et al[:SPECT in subcortical neglect
indexes "AI# for the three clinical categories[ Di}erences between the di}erent clinical categories were larger for AI 0\ AI 1 and AI 2 than for AI 3 and AI 4[ Variable AI 2 exhibited the largest di}erence[ This was also true for median values[ ANOVAs in which AI was taken as a single dependent variable were performed[ Three di}erent factors were considered] neglect "2 levels#\ site "4 levels# and subject[ The latter was treated as a random factor nested in neglect category\ with 02\ 8 and 5 levels respectively for absence of neglect\ moderate and severe neglect[ E}ect of neglect was highly signi_cant ðF"1\14# 05[91^ P ³ 9[994Ł[ E}ect of site was also highly signi_cant ðF"3\099# 3[56^ P ³ 9[994Ł[ The interaction was how! ever just non!signi_cant ðF"7\099# 0[73^ P 9[967Ł[ The fact that the interaction was not signi_cant might suggest that the magnitude of AI di}erences between subgroups did not depend on site[ However\ the inter! action was not far from signi_cance[ Given that sample sizes were fairly small\ the e}ect might reveal itself with slightly larger samples[ Further analyses were performed by taking only two categories for performing the ANOVAs\ namely absence of neglect vs presence of neglect[ The latter category included both subjects with mod! erate neglect and those with severe neglect[ This is sound and has the advantage of increasing sample size and hence the power of the tests[ E}ect of neglect was again highly signi_cant ðF"0\15# 20[57^ P ³ 9[994#[ E}ect of site also remained highly signi_cant ðF"3\093# 3[65^ P ³ 9[994Ł and the interaction became signi_cant ðF"3\093# 12[12^ P 9[904Ł[ This means that e}ect of presence vs absence of neglect on AI depends on site[ Contrasts between neglect e}ects for each pair of sites were also calculated[ Table 2 gives the corresponding F values for the 09 possible site pairs[ Di}erences between AI 3 and AI 2\ AI 3 and AI 1\ and AI 4 and AI 2 were signi_cant without Bonferroni correction[ Only the di}erence between AI 3 and AI 2 remained signi_cant with Bonferroni correction[ This means that interaction between neglect and site is mainly due to the magnitude of the e}ect of neglect between sites 3 and 2 "see Table 1#[ The neglect:site inter! action might also be due to di}erences between sites 3 and 1\ and between 4 and 2[ However\ these di}erences are at the limit of statistical signi_cance[ Table 2[ F values for contrasts between each pair of sites
AI 1 AI 2 AI 3 AI 4
AI 0
AI 1
AI 2
AI 3
9[71 2[54 0[89 9[15
0[90 4[10 1[99
09[72 4[76
9[64
P³9[94 without Bonferroni correction[ P³9[94 with Bonferroni correction[
Discussion In the present study\ neglect was observed in 43) of our cases[ In other studies devoted to subcortical neglect\ the frequencies of occurrence of neglect varied from 14) to 60) ð00\ 04\ 14Ł\ most probably because neuro! psychological batteries of tests of di}erent complexity were used to assess the presence of neglect[ Six patients only presented with severe neglect[ But*in the present study*no patient had a lesion centered on and restricted to the sole thalamus[ Now\ the severity of neglect would be more important in thalamic and cortical lesions ð5\ 14Ł whereas in deep!seated lesions not involving the thala! mus\ the disorder would be rather mild ð5Ł[ Additional cortical damage not seen on CT has already been observed in patients with lenticulostriate infarcts ð01Ł^ such was not the case in our patients assessed with both CT and MRI[ Regarding CT or MRI data\ our observations are in accordance with other previous studies ð00\ 14Ł[ As a rule\ in capsulo!lenticular lesions\ there is no speci_c structure whose injury proved to be necessary and su.cient to provoke neglect[ The analysis of morphological data thus contributes little to the comprehension of the patho! physiology of neglect[ Now\ in deep!seated lesions\ a remote reduction in cortical cerebral blood ~ow or metabolism has been repeatedly observed[ Controversial interpretations regarding the pathophysiology of this phenomenon have been proposed "for a review\ see ð5Ł and ð8Ł#^ but\ the most generally accepted hypothesis ascribed the cortical dysfunction to a disconnection within a neural network leading to a deprivation from a}erent input to the cortex akin to diaschisis[ An additional step was to assume that these remote e}ects could play a role in the patho! physiology of the behavioral disorder[ Till now\ literature data concerned most often left!sided lesions and language disorders[ As stated in the introduction section\ results concerning right!sided lesions and neglect are not con! clusive[ In the present study\ neglect patients could be distinguished from patients without neglect by the pres! ence of a remote decrease in cortical cerebral blood ~ow in the right temporo!parietal region[ This reduction in CBF was slightly more pronounced in patients with sev! ere neglect as compared to the other neglect patients\ the observed di}erences being however not signi_cant[ According to a network approach\ neuropsychological functions are subserved by various cerebral regions including cortical areas\ subcortical grey nuclei and their reciprocal connections[ Disruption of deep!seated neural connections would lead to a remote cortical deprivation from a}erent input[ By assigning a crucial role in spatial attention disorder to a right cortical parieto!temporal dysfunction\ our results suggest that cortical involvement is necessary for the occurrence of cognitive disorders[ Such observation is in accordance with anatomo!clinical studies in which the most frequent correlate of neglect is with cortical retro!rolandic temporo!parietal lesions ð02\
G[ Demeurisse et al[:SPECT in subcortical neglect
14Ł[ Morphological lesions or dysfunction in the same speci_c areas are thus likely to provoke the same clinical syndrome[ Di}erent neural models regarding the modulation of directed spatial attention have been evoked ð6\ 03\ 05\ 10\ 12Ł[ As a rule\ these models pointed out several cortical regions\ i[e[ premotor frontal and parieto!temporal areas[ Our results*showing a temporo!parietal cortical dys! function in neglect patients*are in accordance with these models and stress also the relevant role of posterior regions[ References 0[ Albert\ M[ L[ A simple test of visual neglect[ Neur! olo`y 12\ 547Ð553\ 0862[ 1[ Baron\ J[ C[\ D|Antona\ R[\ Pantano\ P[\ Serdaru\ M[\ Samson\ Y[ and Bousser\ M[ G[ E}ects of thal! amic stroke on energy metabolism of the cerebral cortex[ Brain 098\ 0132Ð0148\ 0875[ 2[ Baron\ J[ C[\ Levasseur\ M[\ Mazoyer\ B[\ Legault! Demare\ F[\ Mauguiere\ F[\ Pappata\ S[\ Jedynak\ P[\ Derome\ P[\ Cambier\ J[\ Tran!Dihn\ S[ and Cambon\ H[ Thalamocortical diaschisis] positron emission tomography in humans[ Journal of Neur! olo`y\ Neurosur`ery and Psychiatry 44\ 824Ð831\ 0881[ 3[ Bogousslavsky\ J[\ Miklossy\ J[\ Regli\ F[\ Deruaz\ J[ P[\ Assal\ G[ and Delaloye\ B[ Subcortical neglect] Neuropsychological\ SPECT\ and neuropathological correlations with anterior choroidal artery territory infarction[ Annals of Neurolo`y 12\ 337Ð341\ 0877[ 4[ Bradvik\ B[\ Sonesson\ B[\ Ryding\ E[ and Rosen\ I[ Spatial and perceptual impairment related to cortical cerebral blood ~ow and EEG in deep white matter infarcts of the right hemisphere[ European Neurolo`y 24\ 79Ð74\ 0884[ 5[ Cappa\ S[ F[ and Vallar\ G[ Neuropsychological dis! orders after subcortical lesions] Implications for neu! ral models of language and spatial attention[ In Neuropsycholo`ical Disorders Associated with Sub! cortical Lesions\ G[ Vallar\ S[ F[ Cappa and C[!W[ Wallesch "Editors#\ pp[ 6Ð30[ Oxford University Press\ Oxford\ 0881[ 6[ De Renzi\ E[\ Gentilini\ M[ and Barbieri\ C[ Auditory neglect[ Journal of Neurolo`y\ Neurosur`ery and Psy! chiatry 41\ 502Ð506\ 0878[ 7[ Duvernoy\ H[ Le cerveau humain[ Surface\ Coupes Seriees Tridimensionnelles et IRM[ Springer Verlag France\ Paris\ 0881[ 8[ Feeney\ D[ and Baron\ J[ C[ Diaschisis[ Stroke 06\ 706Ð729\ 0875[ 09[ Ferro\ J[\ Cantinho\ G[\ Levy\ A[ and Godinho\ F[ Subcortical neglect] is cortical diaschisis relevant< In Neuropsycholo`ical Disorders Associated with Sub! cortical Lesions\ G[ Vallar\ S[ F[ Cappa and C[!W[ Wallesch "Editors#\ pp[ 316Ð325[ Oxford University Press\ Oxford\ 0881[ 00[ Ferro\ J[ M[\ Kertesz\ A[ and Black\ S[ E[ Subcortical neglect] Quantitation\ anatomy and recovery[ Neur! olo`y 26\ 0376Ð0381\ 0876[
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