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].


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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.


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


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


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

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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


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.

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