Review Article …downloads.hindawi.com/journals/schizort/2011/581686.pdfietal lobe are the frontal,...
Transcript of Review Article …downloads.hindawi.com/journals/schizort/2011/581686.pdfietal lobe are the frontal,...
Hindawi Publishing CorporationSchizophrenia Research and TreatmentVolume 2011, Article ID 581686, 15 pagesdoi:10.1155/2011/581686
Review Article
Parietal Lobes in Schizophrenia: Do They Matter?
Murat Yildiz,1 Stefan J. Borgwardt,2 and Gregor E. Berger3
1 Department of Neurology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland2 Psychiatric Outpatient Clinic, University Hospital Basel, 4031 Basel, Switzerland3 Integrierte Psychiatrie Winterthur, Zurich Unterland, 8408 Winterthur, Switzerland
Correspondence should be addressed to Murat Yildiz, [email protected]
Received 7 June 2011; Revised 28 July 2011; Accepted 10 August 2011
Academic Editor: Hugo Schnack
Copyright © 2011 Murat Yildiz et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. Despite observations that abnormal parietal lobe (PL) function is associated with psychotic-like experiences, ourknowledge about the nature of PL involvement in schizophrenia is modest. The objective of this paper is to investigate the role of thePL in schizophrenia. Method. Medline databases were searched for English language publications using the following key words:parietal lobe, combined with schizophrenia, lesions, epilepsy, cognition, rare genetic disorders, MRI, fMRI, PET, and SPECT,respectively, followed by cross-checking of references. Results. Imaging studies in childhood onset schizophrenia suggest that greymatter abnormalities start in parietal and occipital lobes and proceed to frontal regions. Although, the findings are inconsistent,several studies with patients at risk to develop schizophrenia indicate early changes in the PL. Conclusions. We want to propose thatin a proportion of individuals with emerging schizophrenia structural and functional alterations may start in the PL and progressto frontal regions.
1. Introduction
Despite observations that abnormal PL function is associatedwith psychotic-like experiences, our knowledge about thenature of PL involvement in schizophrenia (SZ) is relativelymodest [1]. The PL is engaged in various neuropsychologicalfunctions which are affected in schizophrenic patients [2].The PL supports the frontal lobe in storage and retrieval ofverbal information [3]. Episodic memory encoding dependsnot only on recruiting prefrontal and medial temporal lobesbut also on the activation of PL subregions [4]. The rightinferior and medial parietal cortices have been associatedwith the ability to remember past events and arrange them inthe right chronological order, consequently enabling us toconceive actions as controlled by ourselves and not a thirdperson [5]. Finally, substantial processing for spatial percep-tion, attention, and self-awareness takes place in the parietallobes [6–8].
The PL forms strong anatomical connections with thefrontal lobe [9]. Frontoparietal white matter maturationcorrelates with an increase in grey matter activity in bothlobes during performance of a working memory (WM) taskindicating the close functional connection [10]. Both lobes
are frequently activated together while performing cognitivetasks [11]. Joint activation is characterised by a partiallysymmetrical anteroposterior ordering of activations in bothlobes [12]. Croize et al. demonstrated that although the fron-toparietal network is activated in working memory (WM)tasks, both lobes perform distinctive processes [13].
First, we examine the neuropsychiatric manifestations ofPL lesions, following a review of selected studies investigatingthe PL’s contribution to SZ. The reevaluation of recent find-ings allows us to better understand the scope of the PL’s in-fluence in SZ. Finally, we propose a new disease model forSZ. A speculative hypothesis will be discussed suggesting thatthe timing and location of PL changes may differentiate onemajor pathway in the emergence and progression of SZ.
2. Method
Medline databases were searched for English language publi-cations dating from 1966 to February 2011 using the fol-lowing key words: parietal lobe combined with each of thefollowing key words: schizophrenia, lesions, epilepsy, cog-nition, rare genetic disorders, MRI, fMRI, PET, and SPECT.
2 Schizophrenia Research and Treatment
Cross-checking of references led to the identification ofadditional relevant references.
2.1. The Anatomical Structure. The parietal lobe can bedivided into 3 subregions: the postcentral gyrus, the superiorparietal gyrus, and the inferior parietal lobule, consisting oftwo distinct areas: the angular gyrus and the supramarginalgyrus. The postcentral sulcus separates the postcentral gyrusfrom the superior parietal gyrus and the inferior parietal lob-ule. The posteromedial part of the parietal lobe is called theprecuneus. The boundaries of the medial surface of the par-ietal lobe are the frontal, occipital lobes, and the cingulategyrus. The central sulcus separates the frontal from theparietal lobe. The parieto-occipital fissure lies between theparietal and occipital lobes, and the subparietal sulcus liesbetween the parietal lobe and cingulate gyrus. From the tem-poral lobe, the parietal lobe is separated anteriorly by the Syl-vian fissure [37].
2.2. Parietal Lobe Lesions and Their Neuropsychiatric
Manifestations
2.2.1. Stroke and Other Vascular Conditions. Lesions in thePL offer a unique opportunity to identify the consequences ofaltered PL function (see Table 1). In schizophrenic patients,dysfunctions can be seen which resemble symptoms seen inpatients with PL lesions. Right PL injuries are often resultingin abnormal behaviour such as anosognosia [65]. This con-dition is associated with the denial of any impairment in theface of a hemiparetic limb [66, 67]. Unawareness of disease,lack of insight, is a phenomenon frequently seen in schizo-phrenic patients [68, 69]. Unawareness in SZ might occur inconnection with deficits of executive functions [70] and thusbe very similar to the concept of anosognosia in patients withdetectable damage in the PL [71]. An association betweenstructural damage in the frontal lobe and poor insight intoillness could be established in schizophrenics [72]. The roleof the PL in the phenomenon of unawareness in SZ has yetto be investigated in more detail in the context of the fron-toparietal network.
A more obscure neuropsychiatric manifestations is alienhand syndrome (AHS) that may occur after damage of the PLas well as in other brain regions such as the frontal lobe or thecorpus callosum [73]. The core symptom of AHS is the per-ceived loss of control over one’s own body movements, thatis, a limb. Patients suffer from the impression that an externalforce is responsible for movements of their own limbs; thissymptom is seen occasionally in SZ as well [72]. Sporadically,patients with left PL ischemic lesions display ideomotorapraxia [73, 74] and have difficulties differentiating self-generated movements from foreign made movements [21].Similar findings could be reproduced in healthy participantsusing transcranial magnetic stimulation of the superiorparietal lobule [75]. These findings best correspond to passi-vity phenomena in SZ, which were associated with PL dys-functions [76]. These patients report alien control of theirlimbs due to their inability to align the timing of motor ac-tions internally [77].
Lesions in the posterior parietal cortex highlight the roleof this region in disengaging attention from the current focusto a new one [78]. A deterioration of the ability to shift at-tention has been shown by several research groups in SZ [79].Additionally, patients with PL lesions may experience dif-ficulties to direct attention to the contralateral exterior worldprobably due to a disconnection of parieto-frontal networks[15, 80]. A lateralised defect in the control of attention wasassociated with the severity of symptoms in SZ [81]. Directcomparisons of the performances of schizophrenics and pa-tients with neglect reveal qualitatively similar impairments[82]. Though, in some schizophrenics defects in spatial [83]and temporal perception are not as impressive as neglect seenin patients with PL lesions [84] and may be the reason that ithas not attracted much attention so far.
2.2.2. Parietal Lobe Epilepsy. Focal epilepsy affecting the par-ietal lobe may also present itself with psychotic symptoms.In a retrospective Canadian study of patients with parietallobe epilepsy, most patients experienced aurae, nearly allbeing somatosensory. Some patients described disturbancesof body image, visual illusions, vertiginous sensations, andaphasia. A few patients expressed complex visual or auditoryhallucinations [85]. Parietal lobe epilepsy often cooccurswith temporal lobe epilepsy which is often accompanied withpsychotic like experiences. Marsh et al. described that greymatter volume in the temporal lobes and frontoparietal re-gions was significantly smaller not only in patients with epil-epsy and chronic interictal psychosis but also in patients withunilateral temporal lobe epilepsy without chronic psychosiscompared with healthy control subjects [86].
2.2.3. Rare Genetic Disorders with Parietal Involvement. Velo-cardiofacial (VCF) syndrome is associated with aberrantparietal and frontotemporal white matter tracts. The VCFsyndrome is a rare genetic disorder with a prevalence esti-mated at 1 in 4,000 live births caused by deletion in chromo-some 22q11.2 and characterized by cardiac and facial abnor-malities. 25% of VCF cases present SZ-like symptoms [87]and visuospatial cognitive impairments in adulthood asso-ciated with posterior parietal abnormalities [88]. In VCF,autism spectrum disorders [79] and obsessive-compulsivedisorder [89] occur frequently. Another rare genetic disorder,fragile X syndrome, is associated with impaired visual mo-tion processing involving primarily the PL [90]. Mental re-tardation is the hallmark of fragile X syndrome caused bysilencing of the fragile-X mental retardation (fraX) gene [91].Interestingly, Rivera et al. demonstrated that the parietalregion was more active in patients having a higher expressionof fraX gene [92].
2.3. Parietal Lobes in SZ
2.3.1. Structural Imaging Studies with Parietal Involvementin Childhood-Onset Schizophrenia. Childhood onset schizo-phrenia (COS) is defined by its younger age of onset compar-ed to its adult equivalent and may be a more homogeneousgroup [93]. Studies in COS are particularly important as they
Schizophrenia Research and Treatment 3
Table 1: Studies reporting lesions in parietal lobe.
Investigator Lesion site SubjectsAffectedfunction/impairment
Conclusion Type of study
Danckert et al.2002 [14]
Right PL1 patient with visualneglect
Imagined movements didnot show the samespeed-accuracy trade-offobserved for actualmovements
Right parietal lobe may beimportant in the generationof internal models of motormovements
Case report
Doricchi andTomaiuolo 2004[15]
Right hemisphericdamage
21 pts with neglect10 ctrls
Neglect
Maximal overlap insupramarginal gyrus andsuperior longitudinalfasciculus; decisive role ofparieto-frontaldisconnection in neglect
Case series
Haaland et al.2000 [16]
Left PL41 pts with damage inleft hemisphere
Ideomotor apraxiaRegions in the lefthemisphere important forgoal directed movements
Case series
Markowitsch et al.1999 [17]
Left angular gyruslesion
1 patientAuditory working memorydysfunction
Calculation tasks were notaffected
Case report
Paterson andZangwill 1944 [18]
Penetrating headwound affecting theangular gyrus
1 patient Neglect Case report
Rosler et al. 1997[19]
Ischemic lesion inthe territory of theright middle cerebralartery
31 pts with right- orleft- sided infarctions31 ctrls
Facial recognition ability inpts with right-sided lesionswas lessened comparedwith ctrls and with pts withleft-sided infarctions
Graded impairment inpatients with right middlecerebral artery infarcts
Cross-sectionalcase-controlstudy
Rossetti et al.2005 [20]
First case: bilateralparietal damageSecond case: bilateralposterior parietaland upper and lateraloccipitalcortico-subcorticalregions bilaterallythrough ischemicstroke
2 pts
First case: visualdisorientation,simultanagnosia, andsevere optic ataxiaSecond case: bilateral opticataxia
Optic ataxia patients areimpaired for immediatevisuomotor processing butimprove when required todelay before responding.
Case series
Sirigu et al. 1999[21]
Left parietal cortexdamage
3 pts with apraxia6 ctrls with apraxia2 nonapraxicneurological ctrs
pts were impaired inrecognition of the viewedhand as the examiner’swhen it performedmovements similar to theirown movement
Parietal cortex is importantfor the perception of ownmovements asself-generated
Cross-sectional
PL: parietal lobe; pts: patients; ctrls: healthy controls.
are supposed to be more genetically determined than theadult onset form. As seen in the case of very early onset SZmore severe premorbid neurodevelopmental abnormalities,a higher rate of cytogenetic anomalies and familial SZ are ob-served than in later onset cases [42].
Thompson et al. described that a dynamic wave of greymatter loss occurs, beginning in the PL and proceeding to thetemporal and finally to the prefrontal dorsolateral cortices[94, 95]. The latter findings suggest that the changes in the PLoccur early on in the disease. Although serial brain MRI scansin healthy children over a ten-year period revealed a similarpattern of grey-matter loss beginning in the dorsal par-ietal and primary sensorimotor regions spreading laterally
and caudally into temporal cortices and anteriorly into dor-solateral prefrontal areas [32]. The pattern matches the orderof grey matter loss seen in COS; however, the extend of lossis larger in COS. Additionally, Kyriakopoulos et al. demon-strated that compared with healthy controls, individuals withadolescent-onset SZ showed fractional anisotropy decreasein parietal regions, in contrast to individuals with adult onsetSZ who showed additional fractional anisotropy reductionsin frontal and temporal regions [96]. Fractional anisotropyis measured with diffusion tensor imaging and is positivelycorrelated with the degree of neuronal matura-tion andorganisation of white matter tracts [97]. These findings sup-port the concept of SZ as a neurodegenerative disease [29].
4 Schizophrenia Research and Treatment
Ta
ble
2:R
ecen
tst
ruct
ura
lmag
net
icre
son
ance
imag
ing
(MR
I)an
dco
mpu
teri
zed
tom
ogra
phy
(CT
)st
udi
eson
psyc
hos
isan
dsc
hiz
oph
ren
iaw
ith
rele
van
ceto
the
pari
etal
lobe
.
Inve
stig
ator
sSu
bjec
tgr
oups
Ave
rage
age
offi
rst
scan
(yea
rs)
Ave
rage
year
sof
follo
wu
pIm
age
slic
eth
ickn
ess
met
hod
sof
anal
ysis
Bra
inre
gion
ssh
owin
gsi
gnifi
can
tch
ange
inpa
tien
tsC
orre
lati
ons
betw
een
brai
nch
ange
san
dcl
inic
alva
riab
les
Bu
chan
anet
al.
2004
[22]
44cs
z34
ctrl
s39 34
01.
5m
mR
OI
man
ual
trac
ing
Smal
ler
infe
rior
pref
ron
talr
egio
nvo
l.an
dre
vers
alof
the
nor
mal
asym
met
ryof
the
infe
rior
pari
etal
cort
ex
Can
non
etal
.20
02[2
3]
20M
Zdi
scor
dan
tpa
irs
20D
Zdi
scor
dan
tpa
irs
20M
Zct
rls
20D
Zct
rls
48 49 48 47
01.
2m
mT
hre
e-di
men
sion
alco
rtic
alm
aps
Bet
wee
npa
tien
tsan
dth
eir
MZ
cotw
ins
redu
ced
grey
mat
ter
inth
esu
per
ior
pari
etal
lobu
le,d
orso
late
ralp
refr
onta
lco
rtex
,Bro
ca’s
area
,pre
mot
orco
rtex
and
fron
tale
yefi
elds
,su
peri
orte
mpo
ral
gyru
s.
Dis
ease
-rel
ated
defi
cits
ingr
eym
atte
rw
ere
corr
elat
edw
ith
mea
sure
sof
sym
ptom
seve
rity
and
cogn
itiv
edy
sfu
nct
ion
Daz
zan
etal
.20
11[2
4]10
2U
HR
201
1.5
mm
VB
M
Red
uct
ion
sin
the
fron
talc
orte
xin
subj
ects
wh
ode
velo
ped
psyc
hos
isan
dth
esu
bgro
up
that
subs
equ
entl
yde
velo
ped
SZal
sosh
owed
smal
ler
volu
mes
inth
epa
riet
alco
rtex
Du
bbet
al.
2005
[25]
46cs
z92
ctrl
s29 31
01.
0m
mV
BM
Red
uce
dvo
l.of
the
pari
etal
and
fron
tal
lobe
Foon
get
al.
2001
[26]
25cs
z30
ctrl
s37 35
05.
0m
mM
TI
Fron
tala
nd
tem
pora
lvol
.red
uct
ion
s
Bila
tera
lpar
ieto
-occ
ipit
alco
rtex
and
gen
uof
corp
us
callo
sum
vol.
redu
ctio
ns
wer
eas
soci
ated
wit
hse
veri
tyof
neg
ativ
esy
mpt
oms
insz
Fred
erik
seet
al.
2000
[27]
15m
ale
scz
15fe
mal
ecs
z15
mal
ect
rls
15fe
mal
ect
rls
39 40 39 38
01.
5m
m
RO
Iof
the
infe
rior
pari
etal
lobu
le
Mal
ecs
zh
ada
reve
rsal
ofth
en
orm
alle
ftgr
eate
rth
anri
ght
mal
eas
ymm
etry
and
smal
ler
left
infe
rior
pari
etal
lobu
legr
eym
atte
rvo
l.fe
mal
ecs
zdi
dn
otdi
ffer
from
fem
ale
ctrl
s
Hu
blet
al.
2004
[28]
13cs
zw
ith
toau
dito
ryh
allu
cin
atio
ns
13cs
zw
ith
out
audi
tory
hal
luci
nat
ion
s13
ctrl
s
33 31 320
5.0
mm
DT
I
pts
wit
hh
allu
cin
atio
ns
had
hig
her
wh
ite
mat
ter
dire
ctio
nal
ity
inth
ela
tera
lpar
tsof
the
tem
poro
pari
etal
sect
ion
ofth
ear
cuat
efa
scic
ulu
san
din
part
sof
the
ante
rior
corp
us
callo
sum
Alt
erat
ion
sof
wh
ite
mat
ter
fibe
rtr
acts
inpt
sw
ith
freq
uen
th
allu
cin
atio
ns
lead
toab
nor
mal
coac
tiva
tion
inre
gion
sre
late
dto
the
acou
stic
alpr
oces
sin
g
Job
etal
.20
05[2
9]65
GH
R19
ctrl
s21 21
21.
9m
mV
BM
GH
Rw
ith
righ
tpar
ieta
lgre
ym
atte
r,te
mpo
ralg
rey
mat
ter,
righ
tfr
onta
lgre
ym
atte
rre
duct
ion
s
GH
Rw
ith
psyc
hot
icsy
mpt
oms
and
conv
erte
rssh
owed
adi
ffer
ent
spat
ial
patt
ern
ofre
duct
ion
s
Schizophrenia Research and Treatment 5
Ta
ble
2:C
onti
nu
ed.
Inve
stig
ator
sSu
bjec
tgr
oups
Ave
rage
age
offi
rst
scan
(yea
rs)
Ave
rage
year
sof
follo
wu
pIm
age
slic
eth
ickn
ess
met
hod
sof
anal
ysis
Bra
inre
gion
ssh
owin
gsi
gnifi
can
tch
ange
inpa
tien
tsC
orre
lati
ons
betw
een
brai
nch
ange
san
dcl
inic
alva
riab
les
Jun
get
al.
2009
[30]
29U
HR
31SZ
29ct
rls
22 24 230
voxe
lsiz
e0.
45×
0.45×
0.9
mm
VB
M
UH
R:c
orti
calt
hin
nin
gin
pref
ron
tal
cort
ex,a
nte
rior
cin
gula
teco
rtex
,in
feri
orpa
riet
alco
rtex
,par
ahip
poca
mpa
lcor
tex,
and
supe
rior
tem
pora
lgyr
us
Cor
tica
lth
inn
ing
was
mor
epr
onou
nce
din
SZco
mpa
red
wit
hU
HR
and
ctrl
s
Ku
bick
iet
al.
2001
[31]
16FE
16aff
ecti
veps
ych
osis
18ct
rls
26 23 240
1.5
mm
VB
M
FEre
duce
dvo
lum
eof
righ
tin
feri
orpa
riet
allo
bule
,rig
ht
dors
olat
eral
pref
ron
talc
orte
x,le
ftan
dri
ght
ante
rior
cin
gula
tegy
rus,
left
and
righ
tin
sula
Kyr
iako
pou
los
etal
.200
9[3
2]
17ad
oles
cen
t-on
set
SZ17
adol
esce
nt
ctrl
s17
adu
lt-o
nse
tSZ
17ad
ult
ctrl
s
17 16 24 24
02.
5m
mD
TI
Indi
vidu
als
wit
had
oles
cen
ton
set
SZsh
owfr
acti
onal
anis
otro
pyde
crea
sein
pari
etal
regi
onsi
ndi
vidu
als
wit
had
ult
onse
tsh
owad
diti
onal
lyin
fron
tal,
tem
pora
l,an
dce
rebe
llar
regi
ons
Wh
ite
mat
ter
abn
orm
alit
ies
inSZ
may
depe
nd
onde
velo
pmen
tals
tage
atth
eti
me
ofill
nes
son
set
Min
atog
awa-
Ch
ang
etal
.20
09[3
3]
88FE
P86
ctrl
s29 31
0vo
xels
ize
2×
2×
2m
m3
MR
I+
con
trol
led
oral
wor
das
soci
atio
nte
st+
forw
ard
and
back
war
ddi
git
span
test
s
Vol
um
eab
nor
mal
itie
sin
fron
tala
nd
tem
poro
pari
etal
cort
ices
Cog
nit
ive
defi
cits
dire
ctly
rela
ted
tobr
ain
volu
me
abn
orm
alit
ies
infr
onta
lan
dte
mpo
ropa
riet
alco
rtic
esin
FEP
subj
ects
Mit
elm
anet
al.
2009
[34]
17cs
zw
ith
good
outc
ome
17cs
zw
ith
poor
outc
ome
13ct
rls
37 47 424
1.2
mm
DT
IA
tba
selin
e,cs
zh
adsm
alle
rfr
onta
l,te
mpo
ral,
and
pari
etal
gray
mat
ter
volu
mes
than
ctrl
s
Gre
ym
atte
rvo
lum
esin
poo
r-ou
tcom
epa
tien
tsde
clin
em
ore
rapi
dly
than
inpa
tien
tsw
ith
good
outc
ome
Nar
ret
al.
2005
[35]
72FE
78ct
rls
25 270
1.5
mm
MR
IR
egio
nal
grey
mat
ter
thin
nin
gin
fron
tal,
tem
pora
lan
dpa
riet
alh
eter
omod
alas
soci
atio
nco
rtic
esbi
late
rally
Nie
ren
berg
etal
.20
05[3
6]14
FE14
ctrl
s18
–55
01.
5m
mR
OI
Smal
ler
left
angu
lar
gyru
svo
l.
Niz
nik
iew
icz
etal
.20
00[3
7]
15m
ale
righ
t-h
ande
dcs
z15
mal
eri
ght-
han
ded
ctrl
s
20–5
50
1.5
mm
RO
ISh
owed
are
vers
edas
ymm
etry
inth
ein
feri
orpa
riet
allo
bule
that
was
mai
nly
seen
inth
ean
gula
rgy
rus
6 Schizophrenia Research and Treatment
Ta
ble
2:C
onti
nu
ed.
Inve
stig
ator
sSu
bjec
tgr
oups
Ave
rage
age
offi
rst
scan
(yea
rs)
Ave
rage
year
sof
follo
wu
pIm
age
slic
eth
ickn
ess
met
hod
sof
anal
ysis
Bra
inre
gion
ssh
owin
gsi
gnifi
can
tch
ange
inpa
tien
tsC
orre
lati
ons
betw
een
brai
nch
ange
san
dcl
inic
alva
riab
les
Row
lan
det
al.
2008
[38]
10cs
zw
ith
neg
.sy
mpt
oms
10cs
zw
ith
out
neg
.sy
mpt
oms
11ct
rls
46 40 370
2.2
mm
DT
IR
edu
ced
FAin
the
supe
rior
lon
gitu
din
alfa
scic
ulu
sco
nn
ecti
ng
pari
etal
wit
hfr
onta
llob
e
Supp
ort
for
alte
red
fron
tal-
pari
etal
net
wor
kin
defi
cit
SZ
Schu
ltz
etal
.20
09[3
9]54
FE54
ctrl
s26 27
01
mm
MR
I
Cor
tica
lth
inn
ing
in:d
orso
late
rala
nd
fron
topo
lar
cort
ices
,an
teri
orci
ngu
late
cort
ex,s
upe
rior
tem
pora
lcor
tice
s,an
dsu
per
ior
pari
etal
lobe
Wid
espr
ead
redu
ctio
nof
cort
ical
thic
knes
s,m
ostl
yin
het
erom
odal
cort
ices
offr
onto
tem
por
aln
etw
orks
Sun
2003
[40]
23U
HR
-N12
UH
R-P
20 201
1.5
mm
MR
IU
HR
-P:r
edu
ctio
nin
dors
olat
eral
pref
ron
talc
orte
xan
dor
bito
fron
talc
orte
x
Hig
h-r
isk
psyc
hos
issu
bjec
tssh
owed
orbi
tofr
onta
lcor
tex
redu
ctio
nco
mpa
red
toFE
Sun
etal
.20
05[4
1]
23FE
P(1
6FE
S)11
csz
28ct
rls
22 33 262
1.5
mm
MR
I
FEve
rsus
ctrl
s:w
hol
ebr
ain
,lef
t(t
ren
d),
and
righ
tm
otor
-pre
mot
or,l
efta
ndri
ght
pari
etal
,lef
tan
dri
ght
dors
alpr
efro
nta
lcs
zve
rsus
FE:l
eft
and
righ
tdo
rsal
pref
ron
tal
FEbr
ain
surf
ace
retr
acti
onw
assi
mila
rto
that
ofct
rls
but
sign
ifica
ntl
yac
cele
rate
d
Th
omps
onet
al.
2001
[42]
12SZ
12ct
rls
14 144.
61.
2m
mM
RI
Ear
liest
scan
s:de
fici
tsin
pari
etal
brai
nre
gion
sLa
test
scan
s:in
clu
ded
dors
olat
eral
pref
ron
talc
orte
xan
dsu
peri
orte
mpo
ral
gyri
Ch
ange
patt
ern
sco
rrel
ated
wit
hps
ych
otic
sym
ptom
seve
rity
Wh
itfo
rdet
al.
2005
[43]
31FE
30ct
rls
19 190
1.5
mm
VB
Mle
ftpr
efro
nta
lcor
tex,
left
pari
etal
and
tem
pora
lcor
tex,
righ
tce
rebe
llum
,rig
htpa
riet
al,f
ron
tal,
and
cort
exre
duct
ion
s
Rea
lity
dist
orti
onsy
ndr
ome
scor
eco
rrel
ates
wit
hgr
eym
atte
rre
duct
ion
inFE
Wh
itfo
rdet
al.
2006
[44]
41FE
Sfo
llow
up:
25FE
S47
ctrl
sfo
llow
up:
26ct
rls
19 192.
62.
41.
5m
mV
BM
Bas
elin
e:gr
eym
atte
rre
duct
ion
sin
the
fron
tal,
pari
etal
,an
dte
mpo
ralc
orti
ces
and
cere
bellu
mFo
llow
upin
terv
al:e
spec
ially
inth
epa
riet
alan
dte
mpo
ralc
orti
ces
furt
her
redu
ctio
ns
Nar
ret
al.
2001
[35]
48cs
z48
ctrl
s33 32
00.
9–1.
4m
mV
BM
Left
-dom
inan
tfr
onta
l,te
mpo
ral,
and
insu
lar
grey
mat
ter
redu
ctio
ns
Glo
bala
sses
smen
tof
fun
ctio
nin
gsc
ore
corr
elat
edw
ith
grey
mat
ter
vol.
inth
ele
ftin
feri
orfr
onta
lan
din
feri
orpa
riet
allo
be
Zh
ouet
al.
2006
[45]
53cs
z25
sch
izot
ypal
diso
rder
pts
59ct
rls
25 26 240
1m
mR
OI
csz:
redu
ctio
nin
pari
etal
lobe
sch
izot
ypal
subj
ects
:pos
tcen
tral
gyru
svo
lum
ere
duct
ion
s
csz:
chro
nic
sch
izop
hre
nic
pati
ents
;ct
rls:
hea
lthy
con
trol
s;R
OI:
regi
onof
inte
rest
;vo
l.:vo
lum
e;M
Z:
mon
ozyg
otic
twin
s;D
Z:
dizy
goti
ctw
ins;
VB
M:
Vox
el-B
ased
Mor
phom
etry
;M
TI:
mag
net
izat
ion
tran
sfer
imag
ing;
SZ:
sch
izop
hre
nia
;D
TI:
diff
usi
onte
nso
rim
agin
g;FE
:fi
rst
epis
ode
sch
izop
hre
nia
;FE
P:
firs
tep
isod
eps
ych
osis
;FA
:fr
acti
onal
anis
otro
py;
GH
R:
subj
ects
atge
net
ical
lyh
igh
risk
;U
HR
:u
ltra
-hig
h-r
isk
pati
ents
;UH
R-P
:ult
ra-h
igh
-ris
ksu
bjec
tsw
ho
beca
me
psyc
hot
ic;U
HR
-N:u
ltra
-hig
h-r
isk
subj
ects
wh
odi
dn
otbe
cam
eps
ych
otic
,VB
M:v
oxel
-bas
edm
orph
omet
ry.
Schizophrenia Research and Treatment 7
Ta
ble
3:R
ecen
tfu
nct
ion
alm
agn
etic
reso
nan
ceim
agin
g(M
RI)
and
posi
tron
emis
sion
tom
ogra
phy
(PE
T)
stu
dies
onps
ych
osis
and
sch
izop
hre
nia
wit
hre
leva
nce
toth
epa
riet
allo
be.
Inve
stig
ator
Subj
ect
grou
psA
vera
geag
ePa
radi
gmTe
sted
brai
nfu
nct
ion
Met
hod
ofan
alys
isM
ain
fin
din
gsin
pati
ents
com
pare
dw
ith
ctls
Con
clu
sion
Arc
eet
al.
2006
[46]
17cs
z17
ctrl
s41 40
Vis
ual
Go/
Nog
ota
skw
ith
mat
ched
perf
orm
ance
accu
racy
betw
een
csz
and
ctrl
s
Inh
ibit
ion
and
cue
proc
essi
ng
fMR
I
Dur
ing
cued
inhi
biti
on:g
reat
erac
tiva
tion
inth
ele
ftpr
ecu
neu
san
dle
ftsu
peri
orte
mpo
ralg
yru
sD
urin
gin
hibi
tion
:les
sA
CC
and
DL
PFC
acti
vati
onIm
plic
itcu
etr
ials
:gre
ater
infe
rior
fron
tal
gyru
sac
tiva
tion
Csz
hav
edi
fficu
ltie
sw
ith
inh
ibit
ion
and
clu
epr
oces
sin
g
Bra
us
etal
.20
06[4
7]11
FE11
ctrl
s25 29
Sim
ult
aneo
us
pres
enta
tion
ofac
oust
ical
and
opti
cal
inpu
ts
Bas
icse
nso
ryin
put
circ
uit
sfM
RI
Less
acti
vati
onof
the
PL
,rig
ht
thal
amu
s,th
eri
ght
pref
ron
talc
orte
xA
lrea
dyat
dise
ase
onse
tde
fici
tsin
info
rmat
ion
proc
essi
ng
are
exis
tin
g
Bro
ome
etal
.20
09[4
8]
17U
HR
10FE
P15
ctrl
s
24 26 25
Ver
balfl
uen
cyta
skan
dan
N-b
ack
WM
fMR
I
Act
ivat
ion
patt
ern
inU
HR
was
duri
ng
the
N-b
ack
task
diff
eren
tin
dors
olat
eral
pref
ron
tala
nd
pari
etal
cort
exco
mpa
red
toct
rls
Th
ele
velo
freg
ion
alac
tiva
tion
inth
eU
HR
grou
pw
asin
term
edia
tebe
twee
nth
atin
the
FEgr
oup
and
ctrl
s
Fran
cket
al.
2002
[49]
87cs
z31
Inst
ruct
edto
rela
xan
dn
otp
erfo
rman
yta
sks
Ran
dom
epis
odic
sile
nt
thou
ght
(RE
ST)
PE
T
Sch
nei
deri
ansc
ore
posi
tive
lyco
rrel
ated
wit
hrC
BF
inri
ght
supe
rior
pari
etal
cort
exan
dn
egat
ivel
yco
rrel
ated
wit
hrC
BF
inle
ftpo
ster
ior
cin
gula
tegy
rus
and
inle
ftlin
gual
gyru
s
Fin
din
gssu
ppor
thy
poth
esis
that
cere
bral
patt
ern
ofac
tiva
tion
islin
ked
tosy
mpt
oms
ofSZ
Hen
sele
ret
al.
2010
[50]
12cs
z12
ctrl
s33 32
Ver
bali
tem
-rec
ogn
itio
nta
skan
da
visu
ospa
tial
item
-rec
ogn
itio
nta
skW
MfM
RI
SZsh
owed
redu
ced
con
nec
tivi
tyof
the
pref
ron
talc
orte
xw
ith
the
intr
apar
ieta
lco
rtex
and
the
hip
poca
mpu
s
Alt
ered
pref
ron
to-h
ipp
ocam
pala
nd
pari
eto-
occi
pita
lcon
nec
tivi
tyw
asfo
un
dto
beas
soci
ated
wit
hh
igh
erp
osit
ive
sym
ptom
s
Hu
gdah
let
al.
2004
[51]
csz
depr
esse
dpt
sct
rls
32 33 31
Firs
tta
sk:p
ress
ing
are
spon
sebu
tton
wh
enev
era
spec
ific
nu
mbe
rw
asse
enSe
con
dta
sk:a
ddin
gtw
oco
nse
cuti
ven
um
bers
Vig
ilan
ceta
skM
enta
lar
ith
met
icta
skfM
RI
Less
acti
vati
onin
pref
ron
talb
rain
regi
ons
and
grea
ter
pari
etal
lobe
acti
vati
onre
lati
veco
mpa
red
toct
rls
and
pati
ents
wit
hm
ajor
depr
essi
on.
Insu
ppor
tdo
ubl
edi
ssoc
iati
onof
pari
etal
and
fron
tall
obe
acti
vati
onbe
twee
nSZ
and
depr
essi
on
Kee
dyet
al.
2006
[52]
15FE
24ct
rls
25 25
Eye
mov
emen
tta
sks:
visu
ally
guid
edsa
ccad
e,sm
ooth
purs
uit
para
digm
san
doc
ulo
mot
orde
laye
dre
spon
sepa
radi
gm
Ocu
lom
otor
fun
ctio
nSp
atia
lw
orki
ng
mem
ory
fMR
I
Red
uce
dac
tiva
tion
inse
nso
rim
otor
area
ssu
ppor
tin
gey
em
ovem
ent
con
trol
:pa
riet
alco
rtex
,fro
nta
leye
fiel
ds,
supp
lem
enta
ryey
efi
elds
,an
dci
ngu
late
dco
rtex
Gen
eral
ized
patt
ern
ofco
rtic
aldy
sfu
nct
ion
alre
ady
pres
ent
earl
ySZ
8 Schizophrenia Research and Treatment
Ta
ble
3:C
onti
nu
ed.
Inve
stig
ator
Subj
ect
grou
psA
vera
geag
ePa
radi
gmTe
sted
brai
nfu
nct
ion
Met
hod
ofan
alys
isM
ain
fin
din
gsin
pati
ents
com
pare
dw
ith
ctls
Con
clu
sion
Kes
hav
anet
al.
2002
[53]
4G
HR
4ct
rls
13 13M
emor
y-gu
ided
sacc
ade
task
Spat
ial
wor
kin
gm
emor
yfM
RI
Dec
reas
edac
tiva
tion
inth
ein
feri
orpa
riet
alco
rtex
and
the
DL
PFC
Dys
fun
ctio
nof
pref
ron
tala
nd
pari
etal
regi
ons
inG
HR
Kim
etal
.20
03[5
4]12
csz
12ct
rls
26 26n
-bac
kse
quen
tial
pict
ure
task
WM
PE
TD
orso
late
ralp
refr
onta
l,ve
ntr
olat
eral
pref
ron
tala
nd
bila
tera
lin
feri
orpa
riet
alre
gion
acti
vati
onab
nor
mal
itie
s
Indi
cati
ng
that
duri
ng
wor
kin
gm
emor
yta
sks
ther
eco
uld
bea
pari
etof
ron
tal
disc
onn
ecti
on
On
gur
etal
.20
06[5
5]20
csz
17ct
rls
40 38
Dis
crim
inat
ion
ofpr
evio
usl
yse
enan
dn
ewpa
irs
ofvi
sual
stim
uli
Rel
atio
nal
mem
ory
fMR
IW
hile
disc
rim
inat
ing
nov
elpa
irs
decr
ease
dac
tiva
tion
ofth
eri
ght
pari
etal
cort
exan
dth
ean
teri
orci
ngu
late
cort
ex
Defi
cit
ofre
lati
onal
mem
ory
con
nec
ted
tody
sfu
nct
ion
alac
tiva
tion
ofth
epa
riet
alco
rtex
and
the
hip
poca
mpu
s
Oje
daet
al.
2002
[56]
11cs
zdr
ug
nai
ve10
ctrl
s
28 26
Au
dito
ryst
imu
lati
onta
skC
oun
tin
gta
sks
wit
hor
wit
hou
tau
dito
ryst
imu
lati
on
Att
enti
onta
sks
PE
TIn
adeq
uat
eac
tiva
tion
ofpa
riet
alan
dfr
onta
lreg
ion
sdu
rin
gpe
rfor
man
ceof
cogn
itiv
ely
eman
din
gta
sks
Evid
ence
ofco
mpe
nsa
tory
mec
han
ism
sin
fron
topa
riet
alre
gion
s
Pau
lus
etal
.20
03[5
7]15
scz
15ct
rls
42 41Tw
o-ch
oice
pred
icti
onta
sk
Dec
isio
nm
akin
gw
ith
diff
eren
tde
gree
sof
un
cert
ain
ty
fMR
IP
Lle
ssac
tiva
ted
inde
cisi
onm
akin
gin
situ
atio
ns
wit
hh
igh
un
cert
ain
outc
ome
Inad
equ
ate
proc
essi
ng
insi
tuat
ion
sof
un
cert
ain
tyin
the
post
erio
rpa
riet
alco
rtex
Qu
inta
na
etal
.20
03[5
8]8
sz8
ctrl
sA
nti
cipa
tory
task
Ret
enti
onta
skW
MfM
RI
An
tici
pato
ryta
sk:d
ecre
ased
PFC
and
incr
ease
dP
PC
acti
vati
onR
eten
tion
task
:in
crea
sed
PFC
acti
vati
on
PFC
show
sm
ore
hypo
acti
vati
onth
anP
PC
isab
leto
com
pen
sate
San
zet
al.
2009
[59]
13cs
zn
oin
for-
mat
ion
abou
tct
rls
incl
ude
d
20ve
rbal
capa
city
task
verb
alW
MfM
RI
Low
erle
vels
ofac
tiva
tion
infr
onta
llob
e,P
Lin
the
left
hem
isph
ere
Dys
fun
ctio
nal
acti
vati
ondu
rin
gW
Mpr
oces
sin
gre
late
dto
the
seve
rity
ofn
egat
ive
and
diso
rgan
ized
sym
ptom
s
Sch
nei
der
etal
.20
07[6
0]48
FE57
ctrl
s31 31
2-an
d0-
back
task
s
WM
atte
nti
onco
nn
ecte
dpr
oces
ses
fMR
I
Wor
king
mem
ory:
pari
etal
hypo
acti
vati
ons,
com
bin
edw
ith
hype
rfro
nta
lity
inV
LP
FCA
tten
tion
-con
nec
ted
proc
esse
s:hy
poac
tiva
tion
sin
the
VL
PFC
,su
peri
orte
mpo
ralc
orte
x,th
alam
us
Dys
fun
ctio
nal
cere
bral
net
wor
kn
otab
leto
cope
wit
hre
quir
edac
tiva
tion
for
atte
nti
onan
dW
Mta
sks
Swee
ney
etal
.20
03[6
1]
8cs
zw
ith
audi
tory
hal
luci
na-
tion
s8
ctrl
s
31 29
Fast
vers
us
slow
cove
rtar
ticu
lati
onof
aw
ord
attw
ose
lf-p
aced
rate
s
Pro
cess
ing
inn
ersp
eech
fMR
IR
edu
ced
acti
vati
onin
the
righ
tsu
peri
orte
mpo
ral,
infe
rior
pari
etal
,an
dpa
rah
ippo
cam
palr
egio
ns
SZpa
tien
tsw
ith
audi
tory
hal
luci
nat
ion
sh
ave
aber
ran
tac
tiva
tion
patt
ern
ofbr
ain
regi
ons
Schizophrenia Research and Treatment 9
Ta
ble
3:C
onti
nu
ed.
Inve
stig
ator
Subj
ect
grou
psA
vera
geag
ePa
radi
gmTe
sted
brai
nfu
nct
ion
Met
hod
ofan
alys
isM
ain
fin
din
gsin
pati
ents
com
pare
dw
ith
ctls
Con
clu
sion
Spen
ceet
al.
1997
[1]
7d-
scz
6n
d-sc
z6
ctrl
sN
otst
ated
Perf
orm
ing
mov
emen
tta
skSe
con
dP
ET
4–6
wee
ksaf
ter
firs
tP
ET
Mov
emen
tP
ET
Incr
ease
dri
ght
pari
etal
and
cin
gula
teac
tiva
tion
incs
zw
ith
delu
sion
sof
con
trol
but
ind-
scz
wit
hde
crea
sed
pass
ivit
yde
lusi
onin
seco
nd
scan
hype
ract
ivat
ion
ofri
ght
pari
etal
and
cin
gula
tere
mit
ted
Cer
tain
brai
nre
gion
sin
volv
edin
gen
erat
ing
delu
sion
sof
pass
ivit
y
Th
erm
enos
etal
.20
05[6
2]14
SZ22
ctrl
s38 38
Vis
ual
lett
er2-
back
task
WM
fMR
IG
reat
erac
tiva
tion
inth
eri
ght
med
ial
fron
talg
yru
san
dle
ftin
feri
orpa
riet
allo
bule
/med
ialt
empo
ralg
yru
sre
gion
Het
erom
odal
asso
ciat
ion
cort
ices
show
hig
her
acti
vati
onin
SZdu
rin
gpe
rfor
man
ceof
WoM
task
Wh
alle
yet
al.
2006
[63]
4G
HP-
S26
GH
R-P
27G
HR
-N21
ctrl
s
23 26 27 27
Hay
ling
sen
ten
ceco
mpl
etio
nte
stW
ord
retr
ieva
lfM
RI
and
RO
IG
HR
-Nsh
owed
incr
ease
dac
tiva
tion
ofth
eP
Lan
dth
ean
teri
orci
ngu
late
PL
and
the
lingu
algy
rus
cou
ldbe
use
dto
disc
rim
inat
ebe
twee
nco
nver
tsan
dn
onco
nver
ts
Wh
alle
yet
al.
2004
[64]
21G
HR
-P48
GH
R-N
21ct
rls
25 27 27
Part
ofH
aylin
gse
nte
nce
com
plet
ion
test
Ver
bal
init
iati
onfM
RI
GH
R-P
:in
crea
sed
acti
vati
onin
the
left
infe
rior
pari
etal
lobu
leG
HR
-N:l
ess
acti
vity
inm
edia
lpre
fron
tal,
thal
amic
and
cere
bella
rre
gion
s
Soon
est
chan
ges
inpa
tien
tsw
ith
sym
ptom
sm
aybe
con
nec
ted
tohy
pera
ctiv
atio
nin
the
pari
etal
lobe
csz:
pati
ents
wit
hSZ
;ctr
ls:h
ealt
hyco
ntr
ols;
fMR
I:fu
nct
ion
alm
agn
etic
reso
nan
ceim
agin
g;A
CC
:an
teri
orci
ngu
late
cort
ex;D
LP
FC:d
orso
late
ralp
refr
onta
lcor
tex;
FE:p
atie
nts
wit
hfi
rst-
epis
ode
sch
izop
hre
nia
;PL:
pari
etal
lobe
;UH
R:u
ltra
-hig
hri
skpa
tien
tsw
ith
prod
rom
alsy
mpt
oms
ofsc
hiz
oph
ren
ia;F
EP
:firs
tep
isod
eps
ych
osis
;WM
:wor
kin
gm
emor
y;P
ET
:pos
itro
nem
issi
onto
mog
raph
y;rC
BF:
regi
onal
cere
bral
bloo
dfl
ow;p
ts:p
atie
nts
;GH
R:g
enet
ical
lyde
fin
edh
igh
-ris
kfo
rsc
hiz
oph
ren
ia;P
FC:p
refr
onta
lcor
tex;
PP
C:p
oste
rior
pari
etal
cort
ex;V
LPC
:ven
trol
ater
alpr
efro
nta
lcor
tex;
GH
R-N
:ult
rah
igh
-ris
ksu
bjec
tsw
ho
rem
ain
non
psyc
hot
ic;G
HR
-P:u
ltra
-hig
h-r
isk
subj
ects
wh
obe
cam
eps
ych
otic
;GH
P-S:
ult
ra-h
igh
-ris
ksu
bjec
tsw
ho
beca
me
sch
izop
hre
nic
;nd-
scz:
sch
izop
hre
nic
pati
ents
wit
hou
tdel
usi
onof
con
trol
;d-s
cz:s
chiz
oph
ren
icpa
tien
tsw
ith
delu
sion
ofco
ntr
ol;R
OI:
regi
onof
inte
rest
;SZ
:sch
izop
hre
nia
.
10 Schizophrenia Research and Treatment
2.3.2. Structural Imaging Studies with Parietal Involvement inHigh-Risk Patients. In a longitudinal study over two yearswith a genetically defined high-risk (GHR) cohort fromEdinburgh a significant decline in grey matter density wasfound in the right parietal, right frontal, and temporal lobes[30]. In another study, patients at ultra-high risk (UHR)experiencing prodromal symptoms showed significant cor-tical thinning in the inferior parietal cortex compared tohealthy controls [98]. Borgwardt et al. observed that UHRsubjects who later developed psychosis (converters) showedvolume reductions in the medial and superior parietal, in thefrontal and inferior temporal cortex and in the cerebellum.There were no longitudinal volumetric changes in UHRsubjects who did not develop psychosis (nonconverters) [99].These findings suggest that PL changes may occur prior tothe first psychotic episode. However, a previous study fromPantelis et al. could not trace over one year significant chang-es in the PL of converters. Instead, they demonstrated thatconverters compared to nonconverters show a longitudinalreduction in the grey matter of the right medial temporal,lateral temporal, inferior frontal, and cingulate cortex bilat-erally [39].
2.3.3. Structural Imaging Studies with Parietal Involvementin First-Episode Psychosis and Established Schizophrenia. Re-duced cortical thickness in the parietal and frontal regions isalready evident in first-episode SZ patients (FE) [40]. Itshould be noted that a longitudinal surface contraction infrontal and parietal regions of the cortex was found in FE, butnot in chronic schizophrenics [33, 100]. Prefrontal and tem-poroparietal grey matter volume reductions correlate sig-nificantly with cognitive performance in FE, indicating theclinical importance of such alterations [84].
Converging evidence suggests that chronic schizophren-ics display PL structural abnormalities (see Table 2). Row-land et al. demonstrated with diffusion tensor imaging (DTI)a de-clined fractional anisotropy of white matter tracts con-necting frontal and parietal regions in schizophrenics withnegative symptoms [34]. Intriguingly, in the longitudinalfour-year followup conducted by Mitelman et al., grey mattervolumes in the parietal, frontal, and temporal lobes inschizophrenics with a poor clinical outcome continued todecline more rapidly compared to patients with a good clin-ical outcome [101]. Using three-dimensional cortical surfacemaps, a comparison between schizophrenics compared totheir unaffect-ed monozygotic cotwins revealed deficits inthe superior parietal lobe, dorsolateral prefrontal cortex, andsuperior temporal gyrus [102]. Additionally, a previous studyby the same research group demonstrated that frontal lobegrey matter deficits were present in affected and nonaffectedtwins [48].
2.4. Functional Parietal Lobe Abnormalities
2.4.1. Functional Imaging Studies with Parietal Involvementin at Risk Mental States. Functional MRI (fMRI) studiesindicate that UHR individuals display abnormal activationin the prefrontal and parietal cortex during performance of
WM tasks [63]. Whalley et al. reported promising resultsfrom a recent longitudinal fMRI study in GHR individuals.fMRI data of converters compared to nonconverters showedincreased activation of the PL and decreased activation of theanterior cingulate. However, the PL activation only had highpredictive power if the lingual gyrus was also activated [64].The study was limited as only 4 out of 62 at risk individualsdeveloped SZ. Nevertheless, this study might demonstratethat parietal functional abnormalities are present in high-risksubjects who later become psychotic.
The same study group found in GHR individualsincreased connectivity between the left parietal and leftprefrontal regions compared to healthy controls. The authorsinterpreted the hyperactivation of the PL as compensatory,since there were no differences in performance between thegroups [64]. These results underline that many PL findingsare reported in connection with the frontoparietal network.
2.4.2. Functional Imaging Studies with Parietal Involvementin First-Episode Psychosis and in Chronic Schizophrenia. Pre-frontal cortex dysfunctions have been identified as a keyfactor in SZ [103]. The role of PL dysfunctions still remainsambiguous in SZ. Parietal hypoactivation and ventrolateralprefrontal hyperactivity during WM tasks in FE patientsindicate that frontoparietal networks are impaired early inthe course of the illness [60]. Correspondingly, in patientswith chronic SZ, parietal and frontal cortex activation deficitswere described in WM tasks [104]. There is an increasingbody of studies associating PL dysfunctions with a variety ofsymptoms in chronic SZ [105]. For instance, a PET study cor-related positively regional cerebral blood flow in right supe-rior parietal cortex with the severity of Schneiderian first-rank symptoms (voices conversing or commenting; thoughtbroadcasting, withdrawal or insertion; made actions andthoughts) [49]. Moreover, Menon et al. demonstrated thatthinking disturbance was correlated with deficits in activa-tion in the parietal and the right frontal cortices [104]. Infact, overactivity in the right inferior parietal cortex wasassociated with the presence of delusions of control in a studywith acute psychotic schizophrenics performing movementtasks. Interestingly, the activity in this region returned tonormal levels when patients were symptom-free [1]. Lowerlevels of activation during verbal WM task performance inthe left hemisphere across frontal and parietal regions wereassociated with poorer role functioning and greater severityof negative and disorganised symptoms [59]. A recent studyidentified disturbed parieto-occipital functional connectivityas related with positive symptoms of SZ [50]. These findingsunderline that two core symptoms of SZ, cognitive deficitsand delusions, may be related to malfunctions in the parietallobe [106].
3. Discussion
The nature of the pathological processes underlying progres-sive structural and functional changes in SZ and their exacttiming in the brains remains unclear. Our paper provides aselection of studies indicating that PL lesions and epilepsy
Schizophrenia Research and Treatment 11
may cause psychotic-like symptoms and supports the con-cept that PL abnormalities could be important for SZ andrelated disorders. Structural brain irregularities in PL werefound in imaging studies in COS suggesting that greymatter abnormalities start in parietal and occipital lobes andproceed in a dynamic wave to frontal cortices [42, 94]. Thisillustrates that PL structural alterations may occur early inthe course of illness and points to genetic influences, yet tobe determined [93]. The contribution of genetic factors toparietal involvement in SZ is further supported by a signifi-cant decline in grey matter found over time in GHR subjects[29]. The brain-derived neurotrophic factor (BDNF) couldbe one of the candidate genes for parietal lobe alterationsseen in SZ. Indeed, there was decreased activity in the bila-teral posterior parietal regions in GHR patients with BDNFVal homozygote versus BDNF Met carriers [107].
There is evidence that parietal lobe abnormalities may beonly partially genetically determined as parietal lobe altera-tions were seen in monozygotic twins with SZ but not in theirnonaffected twins [101]. There are studies indicating parietalstructural alterations in the early phase of psychosis [99].However, a reduction in the parietal volume was not foundin the UHR sample from Melbourne [98]. This inconsistencycould be explained by major methodological differences ofboth studies: the study by Borgwardt et al. spanned a timeperiod of 3-4 years and the analysed MRI slices were 1 mmthick, whereas the Melbourne group observed their sampleover 1 year and acquired MRI slices that were 3 mm thick[98, 99]. In a recent UHR study from Melbourne applyingvoxel-based morphometry methodology in 1.5 mm thickMRI slices, reductions in frontal and parietal cortices weredetected in the UHR group who later converted to a psycho-tic disorder compared to those who did not convert [24].
The neurodevelopmental hypothesis suggests that earlyinsults in pregnancy and infancy combined with genetic fac-tors render the brain vulnerable for later development of SZ[108]. However, symptoms usually occur many years afterthe implied first damage [100, 109], hence a second insultwas proposed to explain for the long delay [100]. Here, wewant to propose that in a proportion of patients subsequentlydeveloping SZ, structural and functional alterations maystart in parietal lobes progressing to frontal regions. The“parietal type” of SZ development may clinically present ini-tially with working memory deficits [50, 56, 58, 60] anddisturbed self-conceptualization [1, 84]. The “parietal type”may be more relevant for early onset forms of psychoticdisorders in adolescents, with COS being the most extremevariant. In this model, genetic influences would play a moreprominent role. Additional causative factors, yet to be identi-fied, interacting with brain maturational processes in lateadolescence and early adulthood may be decisive in thetransition to a full-blown psychotic disorder [110]. Such anapproach may enable us to characterise subtypes of SZ basedon structural and functional brain processes and not merelyon pure phenomenology.
The functional interdependency of the parietal and front-al cortices was revealed in GHR subjects with isolated psy-chotic symptoms. They displayed compensatory activationin the left inferior parietal lobule while performing
the Hayling sentence completion task [40]. Additionally,Quintana et al. reported parietal cortex activation in schizo-phrenics as compensatory mechanism for prefrontal cortexdysfunction while performing a working memory task [58].However, Schneider et al. described parietal hypoactivationcombined with hyperfrontality in first-episode schizophreniapatients with poorer performance [60]. In contrast to thestudy by Schneider and colleagues, in the studies con-ducted by Whalley and Quintana no statistical differencesin performance accuracy were found between patients andcontrols. The hyperactivation of the PL may compensate forfrontal hypoactivity, then the network between the frontaland parietal cortices is sufficient; hence tasks can be per-formed adequately. But in case of a disconnection in the fron-toparietal network [50], the PL is not recruited to supportthe frontal lobe. This could lead to an inadequate hyperacti-vation of the frontal lobe leading to poor performance.This hypothesis warrants confirmation in carefully plannedstudies.
Finally, some voxel-based morphometry studies have notfound PL volume reductions in FEP [61, 111] and chronic SZ[108, 112]. More research is required to explore parietal lobefunctions and volumes across different stages of SZ. Whetherthe pattern of parietal lobe changes is suitable for identifyinga more homogeneous subgroup of patients with emergingSZ remains to be determined. Further longitudinal dataare necessary from the earliest stages of SZ, particularly inprepsychotic individuals, to resolve this issue. A better under-standing of the time course of structural and functional brainchanges across different stages of psychotic disorders [109]will finally help us to distinguish between those individualsat incipient risk for a major mental illness and those withmerely a transient crisis in life.
Acknowledgment
Murat Yildiz has received travel Grants from Merck Serono,Bayer AG, and Biogen Idec.
References
[1] S. A. Spence, D. J. Brooks, S. R. Hirsch, P. F. Liddle, J. Meehan,and P. M. Grasby, “A PET study of voluntary movementin schizophrenic patients experiencing passivity phenomena(delusions of alien control),” Brain, vol. 120, no. 11, pp.1997–2011, 1997.
[2] E. Antonova, T. Sharma, R. Morris, and V. Kumari, “Therelationship between brain structure and neurocognition inschizophrenia: a selective review,” Schizophrenia Research,vol. 70, no. 2-3, pp. 117–145, 2004.
[3] J. Jonides, E. H. Schumacher, E. E. Smith et al., “The role ofparietal cortex in verbal working memory,” Journal of Neuros-cience, vol. 18, no. 13, pp. 5026–5034, 1998.
[4] A. E. Cavanna and M. R. Trimble, “The precuneus: a reviewof its functional anatomy and behavioural correlates,” Brain,vol. 129, no. 3, pp. 564–583, 2006.
[5] K. Vogeley, R. Tepest, T. Schneider-Axmann et al., “Auto-mated image analysis of disturbed cytoarchitecture in Brod-mann area 10 in schizophrenia,” Schizophrenia Research, vol.62, no. 1-2, pp. 133–140, 2003.
12 Schizophrenia Research and Treatment
[6] M. F. S. Rushworth, A. Ellison, and V. Walsh, “Complemen-tary localization and lateralization of orienting and motorattention,” Nature Neuroscience, vol. 4, no. 6, pp. 656–661,2001.
[7] D. Thoenissen, K. Zilles, and I. Toni, “Differential involve-ment of parietal and precentral regions in movement prepa-ration and motor intention,” Journal of Neuroscience, vol. 22,no. 20, pp. 9024–9034, 2002.
[8] J. Gottlieb, “From thought to action: the parietal cortex as abridge between perception, action, and cognition,” Neuron,vol. 53, no. 1, pp. 9–16, 2007.
[9] B. Seltzer and D. N. Pandya, “Further observations on parie-to-temporal connections in the rhesus monkey,” Experimen-tal Brain Research, vol. 55, no. 2, pp. 301–312, 1984.
[10] P. J. Olesen, Z. Nagy, H. Westerberg, and T. Klingberg,“Combined analysis of DTI and fMRI data reveals a jointmaturation of white and grey matter in a fronto-parietal net-work,” Cognitive Brain Research, vol. 18, no. 1, pp. 48–57,2003.
[11] J. M. Gurd, K. Amunts, P. H. Weiss et al., “Posterior parietalcortex is implicated in continuous switching between verbalfluency tasks: an fMRI study with clinical implications,”Brain, vol. 125, no. 5, pp. 1024–1038, 2002.
[12] O. Simon, F. Kherif, G. Flandin et al., “Automatized clusteringand functional geometry of human parietofrontal networksfor language, space, and number,” NeuroImage, vol. 23, no. 3,pp. 1192–1202, 2004.
[13] A. C. Croize, R. Ragot, L. Garnero et al., “Dynamics ofparietofrontal networks underlying visuospatial short-termmemory encoding,” NeuroImage, vol. 23, no. 3, pp. 787–799,2004.
[14] J. Danckert, S. Ferber, T. Doherty, H. Steinmetz, D. Nicolle,and M. A. Goodale, “Selective, non-lateralized impairment ofmotor imagery following right parietal damage,” Neurocase,vol. 8, no. 3, pp. 194–204, 2002.
[15] F. Doricchi and F. Tomaiuolo, “The anatomy of neglectwithout hemianopia: a key role for parietal-frontal discon-nection?” NeuroReport, vol. 14, no. 2, pp. 239–243, 2003.
[16] K. Y. Haaland, D. L. Harrington, and R. T. Knight, “Neuralrepresentations of skilled movement,” Brain, vol. 123, no. 11,pp. 2306–2313, 2000.
[17] H. J. Markowitsch, E. Kalbe, J. Kessler, H. M. Von Stock-hausen, M. Ghaemi, and W. D. Heiss, “Short-term memorydeficit after focal parietal damage,” Journal of Clinical andExperimental Neuropsychology, vol. 21, no. 6, pp. 784–797,1999.
[18] A. Paterson and O. L. Zangwill, “Disorders of visual spaceperception associated with lesions of the right cerebral hemi-sphere,” Brain, vol. 67, no. 4, pp. 331–358, 1944.
[19] A. Rosler, S. Lanquillon, and O. Dippel, “Impairment of facialrecognition in patients with right cerebral infarcts quantifiedby computer aided morphing,” Journal of Neurology, Neuro-surgery & Psychiatry, vol. 62, pp. 261–264, 1997.
[20] Y. Rossetti, P. Revol, R. McIntosh et al., “Visually guidedreaching: bilateral posterior parietal lesions cause a switchfrom fast visuomotor to slow cognitive control,” Neuropsy-chologia, vol. 43, no. 2, pp. 162–177, 2005.
[21] A. Sirigu, E. Daprati, P. Pradat-Diehl, N. Franck, and M.Jeannerod, “Perception of self-generated movement follow-ing left parietal lesion,” Brain, vol. 122, no. 10, pp. 1867–1874,1999.
[22] R. W. Buchanan, A. Francis, C. Arango et al., “Morphometricassessment of the heteromodal association cortex in Schizo-phrenia,” American Journal of Psychiatry, vol. 161, no. 2, pp.322–331, 2004.
[23] T. D. Cannon, P. M. Thompson, T. G. M. Van Erp et al., “Cor-tex mapping reveals regionally specific patterns of geneticand disease-specific gray-matter deficits in twins discordantfor schizophrenia,” Proceedings of the National Academy ofSciences of the United States of America, vol. 99, no. 5, pp.3228–3233, 2002.
[24] P. Dazzan, B. Soulsby, A. Mechelli et al., “Volumetric abnor-malities predating the onset of schizophrenia and affectivepsychoses: an MRI study in subjects at ultrahigh risk ofpsychosis,” Schizophrenia Bulletin. In press.
[25] A. Dubb, Z. Xie, R. Gur, R. Gur, and J. Gee, “Characterizationof brain plasticity in schizophrenia using template deforma-tion,” Academic Radiology, vol. 12, no. 1, pp. 3–9, 2005.
[26] J. Foong, M. R. Symms, G. J. Barker et al., “Neuropatholog-ical abnormalities in schizophrenia: evidence from magneti-zation transfer imaging,” Brain, vol. 124, no. 5, pp. 882–892,2001.
[27] M. Frederikse, A. Lu, E. Aylward, P. Barta, T. Sharma, and G.Pearlson, “Sex differences in inferior parietal lobule volumein schizophrenia,” American Journal of Psychiatry, vol. 157,no. 3, pp. 422–427, 2000.
[28] D. Hubl, T. Koenig, W. Strik et al., “Pathways that makevoices: white matter changes in auditory hallucinations,” Arc-hives of General Psychiatry, vol. 61, no. 7, pp. 658–668, 2004.
[29] D. E. Job, H. C. Whalley, E. C. Johnstone, and S. M. Lawrie,“Grey matter changes over time in high risk subjects develop-ing schizophrenia,” NeuroImage, vol. 25, no. 4, pp. 1023–1030, 2005.
[30] W. H. Jung, J. S. Kim, J. H. Jang et al., “Cortical thicknessreduction in individuals at ultra-high-risk for psychosis,”Schizophrenia Bulletin, vol. 37, no. 4, pp. 839–849, 2011.
[31] M. Kubicki, M. E. Shenton, D. F. Salisbury et al., “Voxel-basedmorphometric analysis of gray matter in first episode schizo-phrenia,” NeuroImage, vol. 17, no. 4, pp. 1711–1719, 2002.
[32] M. Kyriakopoulos, R. Perez-Iglesias, J. B. Woolley et al.,“Effect of age at onset of schizophrenia on white matter ab-normalities,” British Journal of Psychiatry, vol. 195, no. 4, pp.346–353, 2009.
[33] T. M. Minatogawa-Chang, M. S. Schaufelberger, A. M.Ayres et al., “Cognitive performance is related to corticalgrey matter volumes in early stages of schizophrenia: apopulation-based study of first-episode psychosis,” Schizo-phrenia Research, vol. 113, no. 2-3, pp. 200–209, 2009.
[34] S. A. Mitelman, E. L. Canfield, R. E. Newmark et al.,“Longitudinal assessment of gray and white matter in chronicschizophrenia: a combined diffusion-tensor and structuralmagnetic resonance imaging study,” The Open NeuroimagingJournal, vol. 3, pp. 31–47, 2009.
[35] K. L. Narr, R. M. Bilder, A. W. Toga et al., “Mapping corticalthickness and gray matter concentration in first episodeschizophrenia,” Cerebral Cortex, vol. 15, no. 6, pp. 708–719,2005.
[36] J. Nierenberg, D. F. Salisbury, J. J. Levitt, E. A. David, R. W.McCarley, and M. E. Shenton, “Reduced left angular gyrusvolume in first-episode schizophrenia,” American Journal ofPsychiatry, vol. 162, no. 8, pp. 1539–1541, 2005.
[37] M. Niznikiewicz, R. Donnino, R. W. McCarley et al., “Abnor-mal angular gyrus asymmetry in schizophrenia,” AmericanJournal of Psychiatry, vol. 157, no. 3, pp. 428–437, 2000.
[38] L. M. Rowland, E. A. Spieker, A. Francis, P. B. Barker, W. T.Carpenter, and R. W. Buchanan, “White matter alterations indeficit schizophrenia,” Neuropsychopharmacology, vol. 34, no.6, pp. 1514–1522, 2009.
Schizophrenia Research and Treatment 13
[39] C. C. Schultz, K. Koch, G. Wagner et al., “Reduced corticalthickness in first episode schizophrenia,” Schizophrenia Re-search, vol. 116, no. 2-3, pp. 204–209, 2010.
[40] D. Sun, G. W. Stuart, S. J. Wood et al., “Progressive frontallobe reduction in first episode psychosis,” Schizophrenia Re-search, vol. 60, p. 208, 2003.
[41] D.-Q. Sun, Longitudinal brain changes in early psychosis: amagnetic resonance imaging study, Ph.D. dissertation, Uni-versity of Melbourne, 2005.
[42] P. M. Thompson, C. Vidal, J. N. Giedd et al., “Mapping ado-lescent brain change reveals dynamic wave of accelerated graymatter loss in very early-onset schizophrenia,” Proceedings ofthe National Academy of Sciences of the United States of Ameri-ca, vol. 98, no. 20, pp. 11650–11655, 2001.
[43] T. J. Whitford, T. F. D. Farrow, L. Gomes, J. Brennan, A.W. F. Harris, and L. M. Williams, “Grey matter deficits andsymptom profile in first episode schizophrenia,” PsychiatryResearch, vol. 139, no. 3, pp. 229–238, 2005.
[44] T. J. Whitford, S. M. Grieve, T. F. D. Farrow et al., “Progressivegrey matter atrophy over the first 2-3 years of illness in first-episode schizophrenia: a tensor-based morphometry study,”NeuroImage, vol. 32, no. 2, pp. 511–519, 2006.
[45] S. Y. Zhou, M. Suzuki, T. Takahashi et al., “Parietal lobevolume deficits in schizophrenia spectrum disorders,” Schizo-phrenia Research, vol. 89, no. 1-3, pp. 35–48, 2007.
[46] E. Arce, D. S. Leland, D. A. Miller, A. N. Simmons, K. C.Winternheimer, and M. P. Paulus, “Individuals with schizo-phrenia present hypo- and hyperactivation during implicitcueing in an inhibitory task,” NeuroImage, vol. 32, no. 2, pp.704–713, 2006.
[47] D. F. Braus, W. Weber-Fahr, H. Tost, M. Ruf, and F. A. Henn,“Sensory information processing in neuroleptic-naive first-episode schizophrenic patients: a functional magnetic reson-ance imaging study,” Archives of General Psychiatry, vol. 59,no. 8, pp. 696–701, 2002.
[48] M. R. Broome, P. Matthiasson, P. Fusar-Poli et al., “Neuralcorrelates of executive function and working memory in the‘at-risk mental state’,” British Journal of Psychiatry, vol. 194,no. 1, pp. 25–33, 2009.
[49] N. Franck, D. S. O’Leary, M. Flaum, R. D. Hichwa, and N.C. Andreasen, “Cerebral blood flow changes associated withSchneiderian first-rank symptoms in Schizophrenia,” Journalof Neuropsychiatry and Clinical Neurosciences, vol. 14, no. 3,pp. 277–282, 2002.
[50] I. Henseler, P. Falkai, and O. Gruber, “Disturbed functionalconnectivity within brain networks subserving domain-specific subcomponents of working memory in schizophre-nia: relation to performance and clinical symptoms,” Journalof Psychiatric Research, vol. 44, no. 6, pp. 364–372, 2010.
[51] K. Hugdahl, B. R. Rund, A. Lund et al., “Brain activationmeasured with fMRI during a mental arithmetic task inSchizophrenia and major depression,” American Journal ofPsychiatry, vol. 161, no. 2, pp. 286–293, 2004.
[52] S. K. Keedy, C. L. Ebens, M. S. Keshavan, and J. A. Sweeney,“Functional magnetic resonance imaging studies of eyemovements in first episode schizophrenia: smooth pur-suit,visually guided saccades and the oculomotor delayed res-ponse task,” Psychiatry Research, vol. 146, no. 3, pp. 199–211,2006.
[53] M. S. Keshavan, V. A. Diwadkar, S. M. Spencer, K. A.Harenski, B. Luna, and J. A. Sweeney, “A preliminary func-tional magnetic resonance imaging study in offspring ofschizophrenic parents,” Progress in Neuro-Psychopharma-cology and Biological Psychiatry, vol. 26, no. 6, pp. 1143–1149,2002.
[54] J. J. Kim, J. S. Kwon, J. P. Hae et al., “Functional disconnectionbetween the prefrontal and parietal cortices during workingmemory processing in schizophrenia: a [15(O)] H2O PETstudy,” American Journal of Psychiatry, vol. 160, no. 5, pp.919–923, 2003.
[55] D. Ongur, T. J. Cullen, D. H. Wolf et al., “The neural basisof relational memory deficits in schizophrenia,” Archives ofGeneral Psychiatry, vol. 63, no. 4, pp. 356–365, 2006.
[56] N. Ojeda, F. Ortuno, J. Arbizu et al., “Functional neu-roanatomy of sustained attention in schizophrenia: contribu-tion of parietal cortices,” Human Brain Mapping, vol. 17, pp.116–130, 2002.
[57] M. P. Paulus, L. Frank, G. G. Brown, and D. L. Braff,“Schizophrenia subjects show intact success-related neuralactivation but impaired uncertainty processing during deci-sion-making,” Neuropsychopharmacology, vol. 28, no. 4, pp.795–806, 2003.
[58] J. Quintana, T. Wong, E. Ortiz-Portillo et al., “Prefrontal-posterior parietal networks in schizophrenia: primary dys-functions and secondary compensations,” Biological Psychi-atry, vol. 53, no. 1, pp. 12–24, 2003.
[59] J. H. Sanz, K. H. Karlsgodt, C. E. Bearden et al., “Symptom-atic and functional correlates of regional brain physiologyduring working memory processing in patients with recentonset schizophrenia,” Psychiatry Research, vol. 173, no. 3, pp.177–182, 2009.
[60] F. Schneider, U. Habel, M. Reske et al., “Neural correlates ofworking memory dysfunction in first-episode schizophreniapatients: an fMRI multi-center study,” Schizophrenia Re-search, vol. 89, no. 1-3, pp. 198–210, 2007.
[61] J. A. Sweeney, T. Li, Q. Gong et al., “Association of cerebraldeficits with clinical symptoms in antipsychotic-naive first-episode schizophrenia: an optimized voxel-based morphom-etry and resting state functional connectivity study,” Ameri-can Journal of Psychiatry, vol. 166, no. 2, pp. 196–205, 2009.
[62] H. W. Thermenos, J. M. Goldstein, S. L. Buka et al., “Theeffect of working memory performance on functional MRIin schizophrenia,” Schizophrenia Research, vol. 74, no. 2-3, pp.179–194, 2005.
[63] H. C. Whalley, E. Simonotto, W. Moorhead et al., “Functionalimaging as a predictor of schizophrenia,” Biological Psychia-try, vol. 60, no. 5, pp. 454–462, 2006.
[64] H. C. Whalley, E. Simonotto, S. Flett et al., “fMRI correlatesof state and trait effects in subjects at genetically enhancedrisk of schizophrenia,” Brain, vol. 127, no. 3, pp. 478–490,2004.
[65] G. Berlucchi and S. Aglioti, “The body in the brain: neuralbases of corporeal awareness,” Trends in Neurosciences, vol.20, no. 12, pp. 560–564, 1997.
[66] J. W. Cooney and M. S. Gazzaniga, “Neurological disordersand the structure of human consciousness,” Trends in Cogni-tive Sciences, vol. 7, no. 4, pp. 161–165, 2003.
[67] V. S. Ramachandran, D. Rogers-Ramachandran, and S. Cobb,“Touching the phantom limb,” Nature, vol. 377, no. 6549, pp.489–490, 1995.
[68] E. Kraepelin, Dementia Praecox, Churchill Livingston, NewYork, NY, USA, 1919.
[69] X. F. Amador and J. M. Gorman, “Psychopathologic domainsand insight in schizophrenia,” Psychiatric Clinics of NorthAmerica, vol. 21, no. 1, pp. 27–42, 1998.
[70] S. Sevy, K. Nathanson, H. Visweswaraiah, and X. Amador,“The relationship between insight and symptoms in schizo-phrenia,” Comprehensive Psychiatry, vol. 45, no. 1, pp. 16–19,2004.
14 Schizophrenia Research and Treatment
[71] L. Pia and M. Tamietto, “Unawareness in schizophrenia: neu-ropsychological and neuroanatomical findings,” Psychiatryand Clinical Neurosciences, vol. 60, no. 5, pp. 531–537, 2006.
[72] M. U. Shad, S. Muddasani, K. Prasad, J. A. Sweeney, and M.S. Keshavan, “Insight and prefrontal cortex in first-episodeSchizophrenia,” NeuroImage, vol. 22, no. 3, pp. 1315–1320,2004.
[73] M. A. Kikkert, G. M. Ribbers, and P. J. Koudstaal, “Alien handsyndrome in stroke: a report of 2 cases and review of theliterature,” Archives of Physical Medicine and Rehabilitation,vol. 87, no. 5, pp. 728–732, 2006.
[74] L. J. Buxbaum, S. H. Johnson-Frey, and M. Bartlett-Williams,“Deficient internal models for planning hand-object interac-tions in apraxia,” Neuropsychologia, vol. 43, no. 6, pp. 917–929, 2005.
[75] P. A. MacDonald and T. Paus, “The role of parietal cortexin awareness of self-generated movements: a transcranialmagnetic stimulation study,” Cerebral Cortex, vol. 13, no. 9,pp. 962–967, 2003.
[76] J. Danckert, M. Saoud, and P. Maruff, “Attention, motorcontrol and motor imagery in schizophrenia: implications forthe role of the parietal cortex,” Schizophrenia Research, vol.70, no. 2-3, pp. 241–261, 2004.
[77] P. Maruff, P. Wilson, and J. Currie, “Abnormalities of motorimagery associated with somatic passivity phenomena inschizophrenia,” Schizophrenia Research, vol. 60, no. 2-3, pp.229–238, 2003.
[78] M. I. Posner, J. A. Walker, F. J. Friedrich, and R. D. Rafal,“Effects of parietal injury on covert orienting of attention,”Journal of Neuroscience, vol. 4, no. 7, pp. 1863–1874, 1984.
[79] S. Jazbec, C. Pantelis, T. Robbins, T. Weickert, D. R. Wein-berger, and T. E. Goldberg, “Intra-dimensional/extra-dimen-sional set-shifting performance in schizophrenia: impact ofdistractors,” Schizophrenia Research, vol. 89, no. 1-3, pp. 339–349, 2007.
[80] G. Vallar, “Extrapersonal visual unilateral spatial neglect andits neuroanatomy,” NeuroImage, vol. 14, no. 1, pp. S52–S58,2001.
[81] S. A. Harvey, E. Nelson, J. W. Haller, and T. S. Early,“Lateralization attentional abnormality in schizophrenia iscorrelated with severity of symptoms,” Biological Psychiatry,vol. 33, no. 2, pp. 93–99, 1993.
[82] C. Cavezian, Y. Rossetti, J. Danckert, T. d’Amato, J. Dalery,and M. Saoud, “Exaggerated leftward bias in the mentalnumber line of patients with schizophrenia,” Brain and Cog-nition, vol. 63, no. 1, pp. 85–90, 2007.
[83] C. Cavezian, J. Danckert, J. Lerond, J. Dalery, T. d’Amato, andM. Saoud, “Visual-perceptual abilities in healthy controls,depressed patients, and schizophrenia patients,” Brain andCognition, vol. 64, no. 3, pp. 257–264, 2007.
[84] C. Cavezian, C. Striemer, M. Saoud, Y. Rossetti, and J. Dan-ckert, “Schizophrenia and the neglect syndrome: parietalcontributions to cognitive dysfunction in schizophrenia,”Current Psychiatry Reviews, vol. 2, no. 4, pp. 439–451, 2006.
[85] V. Salanova, F. Andermann, T. Rasmussen, A. Olivier, and L.F. Quesney, “Parietal lobe epilepsy. Clinical manifestationsand outcome in 82 patients treated surgically between 1929and 1988,” Brain, vol. 118, no. 3, pp. 607–627, 1995.
[86] L. Marsh, E. V. Sullivan, M. Morrell, K. O. Lim, and A. Pfef-ferbaum, “Structural brain abnormalities in patients withschizophrenia, epilepsy, and epilepsy with chronic interictalpsychosis,” Psychiatry Research, vol. 108, no. 1, pp. 1–15,2001.
[87] N. Barnea-Goraly, V. Menon, B. Krasnow, A. Ko, A. Reiss, andS. Eliez, “Investigation of white matter structure in velocar-diofacial syndrome: a diffusion tensor imaging study,” Amer-ican Journal of Psychiatry, vol. 160, no. 10, pp. 1863–1869,2003.
[88] J. Burn and J. Goodship, “Developmental genetics of theheart,” Current Opinion in Genetics and Development, vol. 6,no. 3, pp. 322–325, 1996.
[89] C. S. Kogan, A. Bertone, K. Cornish et al., “Integrative corti-cal dysfunction and pervasive motion perception deficit infragile X syndrome,” Neurology, vol. 63, no. 9, pp. 1634–1639,2004.
[90] G. Turner, T. Webb, S. Wake, and H. Robinson, “Prevalenceof fragile X syndrome,” American Journal of Medical Genetics,vol. 64, no. 1, pp. 196–197, 1996.
[91] S. M. Rivera, V. Menon, C. D. White, B. Glaser, and A. L.Reiss, “Functional brain activation during arithmetic pro-cessing in females with fragile X syndrome is related to FMRIprotein expression,” Human Brain Mapping, vol. 16, no. 4,pp. 206–218, 2002.
[92] B. Childs and C. R. Scriver, “Age at onset and causes of dis-ease,” Perspectives in Biology and Medicine, vol. 29, no. 3, pp.437–460, 1986.
[93] R. Nicolson and J. L. Rapoport, “Childhood-onset schizo-phrenia: rare but worth studying,” Biological Psychiatry, vol.46, no. 10, pp. 1418–1428, 1999.
[94] A. W. Toga, P. M. Thompson, and E. R. Sowell, “Mappingbrain maturation,” Trends in Neurosciences, vol. 29, no. 3, pp.148–159, 2006.
[95] N. Gogtay, A. Sporn, L. S. Clasen et al., “Structural brain MRIabnormalities in healthy siblings of patients with childhood-onset schizophrenia,” American Journal of Psychiatry, vol.160, no. 3, pp. 569–571, 2003.
[96] C. Beaulieu, “The basis of anisotropic water diffusion in thenervous system—a technical review,” NMR in Biomedicine,vol. 15, no. 7-8, pp. 435–455, 2002.
[97] I. Feinberg, “Schizophrenia: caused by a fault in programmedsynaptic elimination during adolescence?” Journal of Psychi-atric Research, vol. 17, no. 4, pp. 319–334, 1982.
[98] C. Pantelis, M. Yucel, S. J. Wood, P. D. McGorry, and D.Velakoulis, “Early and late neurodevelopmental disturbancesin schizophrenia and their functional consequences,” Austra-lian and New Zealand Journal of Psychiatry, vol. 37, no. 4, pp.399–406, 2003.
[99] S. J. Borgwardt, P. K. McGuire, J. Aston et al., “Reductionsin frontal, temporal and parietal volume associated with theonset of psychosis,” Schizophrenia Research, vol. 106, no. 2-3,pp. 108–114, 2008.
[100] C. Pantelis, M. Yucel, S. J. Wood et al., “Structural brainimaging evidence for multiple pathological processes atdifferent stages of brain development in schizophrenia,”Schizophrenia Bulletin, vol. 31, no. 3, pp. 672–696, 2005.
[101] S. J. Borgwardt, M. M. Picchioni, U. Ettinger, T. Toulopoulou,R. Murray, and P. K. McGuire, “Regional gray mattervolume in monozygotic twins concordant and discordant forschizophrenia,” Biological Psychiatry, vol. 67, no. 10, pp. 956–964, 2010.
[102] T. D. Cannon, M. O. Huttunen, J. Lonnqvist et al., “Theinheritance of neuropsychological dysfunction in twins dis-cordant for schizophrenia,” American Journal of HumanGenetics, vol. 67, no. 2, pp. 369–382, 2000.
[103] D. R. Weinberger, “Prefrontal function in schizophrenia:confounds and controversies,” Philosophical Transactions ofthe Royal Society B, vol. 351, no. 1346, pp. 1495–1503, 1996.
Schizophrenia Research and Treatment 15
[104] V. Menon, R. T. Anagnoson, D. H. Mathalon, G. H. Glover,and A. Pfefferbaum, “Functional neuroanatomy of auditoryworking memory in schizophrenia: relation to positive andnegative symptoms,” NeuroImage, vol. 13, no. 3, pp. 433–446,2001.
[105] A. P. Weiss, C. B. Ellis, J. L. Roffman et al., “Aberrant fronto-parietal function during recognition memory in schizophre-nia: a multimodal neuroimaging investigation,” Journal ofNeuroscience, vol. 29, no. 36, pp. 11347–11359, 2009.
[106] G. D. Pearlson, R. G. Petty, C. A. Ross, and A. Y. Tien,“Schizophrenia: a disease of heteromodal association cor-tex?” Neuropsychopharmacology, vol. 14, no. 1, pp. 1–17,1996.
[107] B. J. Baig, H. C. Whalley, J. Hall et al., “Functional magneticresonance imaging of BDNF val66met polymorphism inunmedicated subjects at high genetic risk of schizophreniaperforming a verbal memory task,” Psychiatry Research, vol.183, no. 3, pp. 195–201, 2010.
[108] J. M. Segall, J. A. Turner, T. G. M. Van Erp et al., “Voxel-based morphometric multisite collaborative study on schizo-phrenia,” Schizophrenia Bulletin, vol. 35, no. 1, pp. 82–95,2009.
[109] P. D. McGorry, I. B. Hickie, A. R. Yung, C. Pantelis, andH. J. Jackson, “Clinical staging of psychiatric disorders: aheuristic framework for choosing earlier, safer and moreeffective interventions,” Australian and New Zealand Journalof Psychiatry, vol. 40, no. 8, pp. 616–622, 2006.
[110] H. Sakata, M. Taira, M. Kusunoki, A. Murata, and Y. Tanaka,“The TINS lecture: the parietal association cortex in depthperception and visual control of hand action,” Trends inNeurosciences, vol. 20, no. 8, pp. 350–357, 1997.
[111] A. K. Malla, M. Bodnar, R. Joober, and M. Lepage, “Durationof untreated psychosis is associated with orbital-frontal greymatter volume reductions in first episode psychosis,” Schizo-phrenia Research, vol. 125, no. 1, pp. 13–20, 2011.
[112] W. Y. Chan, M. Y. Chia, G. L. Yang et al., “Duration of illness,regional brain morphology and neurocognitive correlates inschizophrenia,” Annals of the Academy of Medicine Singapore,vol. 38, no. 5, pp. 388–395, 2009.
Submit your manuscripts athttp://www.hindawi.com
Stem CellsInternational
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Disease Markers
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014
Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Parkinson’s Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com