Functional deHcits of the attentional networks in autism

1ih Fah , Silvia 8erhardi , Nicholas 1. Vah Dam , Lvdokia AhaghosIou , Xiaosi Gu ,
Laura MarIih , Yuhsoo Park , Xuh Liu , Alexahder Kolevzoh , LaIha Soorya , David Grodberg ,
Lric Hollahder & PaIrick R. Ho!
Deparlmenl ol Psychology, Queens College, Cily Universily ol New York, New York
Deparlmenl ol Psychialry, Mounl Sinai School ol Medicine, New York
lishberg Deparlmenl ol Neuroscience and lriedman 8rain lnslilule, Mounl Sinai School ol Medicine, New York
Seaver Aulism Cenler lor Pesearch and Trealmenl, Mounl Sinai School ol Medicine, New York
Alberl Linslein College ol Medicine and Monlelore Medical Cenler, New York
Keyvords
Alerling, anlerior cingulale corlex, allenlional
nelworks, aulism, execulive conlrol
Correspondence
Jin lan, Deparlmenl ol Psychology, Queens
College, Cily Universily ol New York,
65-30 Kissena 8lvd. llushing, NY !!367.
Tel. 7!8-997-4!39, lax. 7!8-570-0363,
L-mail. jin.lanqc.cuny.edu
funding In!ormation
This work was supporled by Nalional Cenler
lor Pesearch Pesources (NCPP) Cranl M0!
PP00007!. lls conlenls are solely lhe
responsibilily ol lhe aulhors and do nol
necessarily represenl lhe ollcial views ol
NCPP or Nalional lnslilule ol Menlal Heallh
(NlMH). This work was also supporled in,
parl by, Seaver Aulism Cenler lor Pesearch
and Trealmenl al Mounl Sinai School ol
Medicine, by Nalional lnslilules ol Heallh
(NlH) granl P2! MH083!64 (lo J. l.), and
by lhe James S. McDonnell loundalion
(lo P. P. H.).
Peceived. 30 March 20!2, Pevised. 20 July
20!2, Accepled. 30 July 20!2
8rain and 8ehavior 2012, 2(5). 647-660
doi. !0.!002/brb3.90
Abstract
Attentional dysfunction is among the most consistent obseivations of autism
spectium disoideis (ASD). Howevei, the neuial natuie of this defcit in ASD is
still uncleai. In this study, we aimed to identify the neuiobehavioial coiielates
of attentional dysfunction in ASD. We used the Attention Netwoik Test-
Revised and functional magnetic iesonance imaging to examine aleiting, oiient-
ing, and executive contiol functions, as well as the neuial substiates undeilying
these attentional functions in unmedicated, high-functioning adults with ASD
(n 12) and matched healthy contiols (HC, n 12). Compaied with HC,
individuals with ASD showed incieased eiioi iates in aleiting and executive
contiol, accompanied by lowei activity in the mid-fiontal gyius and the caudate
nucleus foi aleiting, and by the absence of signifcant functional activation in
the anteiioi cingulate coitex (ACC) foi executive contiol. In addition, gieatei
behavioial defciency in executive contiol in ASD was coiielated with less func-
tional activation of the ACC. These fndings of behavioial and neuial abnoi-
malities in aleiting and executive contiol of attention in ASD may suggest coie
attentional defcits, which iequiie fuithei investigation.
lntroduction
Autism spectium disoideis (ASD) aie neuiodevelopmen-
tal disoideis chaiacteiized by defcits in social inteiaction,
communication, as well as steieotyped and iepetitive
behaviois, and iestiicted inteiest in domains of activity.
Although attentional dysfunction is one of the most con-
sistently iepoited cognitive defcits in autism (Allen and
Couichesne, 2001), the specifc components and compo-
nent inteiactions in the attentional netwoiks that aie
impaiied in ASD iemain uncleai. An investigation of
attentional functions and ielated biain netwoiks could
piovide moie compiehensive infoimation about poten-
tially impoitant coie defcits foi ieseaich, diagnosis, and
tieatment of ASD.
We conceptualize attention as consisting of thiee dis-
tinct functional components: aleiting, oiienting, and exec-
utive contiol (Posnei and Fan 2008). The alerting
function subsumes the capacity to inciease vigilance toni-
cally (i.e., incieased vigilance ielated to incieased geneial
aiousal), oi phasically (i.e., incieased vigilance ielated to
a specifc stimulus) to piocess an impending stimulus.
20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc. This is an open access arlicle under lhe lerms ol
lhe Crealive Commons Allribulion-NonCommercial License, which permils use, dislribulion and reproduclion in any medium,
provided lhe original work is properly ciled and is nol used lor commercial purposes.
647
The crienting function suppoits the selection of specifc
infoimation fiom numeious sensoiy inputs. Oiienting
involves iapid oi slow shifting of attention among taigets
within oi between modalities, with thiee elementaiy opei-
ations: disengaging attention fiom its cuiient focus, mov-
ing attention to the new taiget, and engaging attention at
the new taiget (Posnei et al. 1984). The executive ccntrcl
of attention involves the engagement of moie complex
mental opeiations duiing detection and iesolution of
conict between competing goals oi functions.
Each of the thiee attentional functions is mediated by
anatomically distinct neuial netwoiks (Fan et al. 2005).
Aleiting has been associated with the thalamus and the
tempoiopaiietal junction (TPJ) and othei paiietal iegions
(Fan et al. 2005). Additionally, the mid-fiontal gyius
(MFG a pait of the doisolateial piefiontal coitex,
DLPFC), as well as the caudate nucleus and putamen, has
been implicated in effcient piocessing of waining signals
involved in geneiating an anticipatoiy iesponse (Fan et al.
2007; Cleikin et al. 2009). The oiienting system foi visual
events has been associated with the supeiioi paiietal lob-
ule and the fiontal eye felds (FEF) (Coibetta and Shul-
man 2002). It has been shown that the aieas neai and
along the intiapaiietal sulcus (IPS) bilateially and the FEF
aie involved in oiienting, wheieas the iight TPJ and infe-
iioi fiontal gyius aie involved in ieoiienting (Coibetta
et al. 2008). Finally, executive contiol of attention
involves the anteiioi cingulate coitex (ACC) and DLPFC
(Matsumoto and Tanaka 2004). A numbei of neuioimag-
ing studies have shown activation of the doisal ACC in
tasks iequiiing subjects to iespond to one dimension of a
stimulus instead of anothei stiong, conicting dimension
(e.g., Bush et al. 2000; Botvinick et al. 2001; Fan et al.
2003).
Individuals with ASD have shown defcits in all thiee
attentional functions. The Continuous Peifoimance Test
(CPT) (Rosvold et al. 1956) is the most commonly used
paiadigm foi exploiing the aleiting function in autism;
most iesults suggest a noimal ability of ASD individuals
to sustain attention (Gaiietson et al. 1990; Siegel et al.
1992; Pascualvaca et al. 1998). Howevei, when the AX
veision of the CPT (subject iesponds to the taiget X"
when it is pieceded by an A" compaied with the taiget
pieceded by othei letteis) was employed, childien with
autism showed a tiend of benefting less fiom the A"
cue, suggesting an abnoimal phasic aleiting function
(Pascualvaca et al. 1998).
Oiienting defcits aie shown in tasks that iequiie iapid
shifting of attention between modalities (Couichesne
et al. 1994a), between object featuies (Couichesne et al.
1994a,b; Rinehait et al. 2001), and between spatial loca-
tions (Wainwiight-Shaip and Biyson 1993; Townsend
et al. 1996a,b, 1999; Wainwiight and Biyson 1996; Haiiis
et al. 1999; Belmonte 2000). These defcits occui foi audi-
toiy and visual taigets sepaiately (Lovaas et al. 1971,
1979; Townsend and Couichesne 1994) and jointly (Casey
et al. 1993), as well as acioss diffeient manipulations of
attention adjusting and updating the scope of attention
(Buiack et al. 1997), engaging visual attention (Buiack
1994), and disengaging attention (Wainwiight and Biyson
1996). Oiienting defcits in autism have been shown to be
ielated to abnoimalities in paiietal lobe stiuctuie (Coui-
chesne et al. 1993; Townsend and Couichesne 1994).
Although many studies have shown that oiienting defcits
in individuals with autism aie ielated to social cues (e.g.,
Dawson et al. 1998), especially human faces, othei studies
piovide evidence of nonspecifc oiienting defcits (Landiy
and Biyson 2004; Tedei-Salejaivi et al. 2005). Although
defcits in spatial oiienting have been documented (e.g.,
Casey et al. 1993; Townsend et al. 1996a) and have been
shown to ielate to stiuctuial abnoimalities in the ceiebel-
lum and paiietal lobe (Couichesne et al. 1993; Townsend
et al. 1996a), the neuial mechanisms of oiienting defcits,
especially in the context of joint attention, still iemain
uncleai.
Behavioial studies have been conducted to examine
whethei theie aie defcits in executive contiol of attention
in ASD using cognitive paiadigms such as the Go/No-Go
and the Stioop tasks. Although executive contiol dysfunc-
tion may be attiibuted to fiontal lobe abnoimalities that
have been obseived in individuals with autism
(Couichesne et al. 2001; Spaiks et al. 2002), theie is no
consistent evidence suppoiting impaiied inhibition, foi
example, on the Stioop task (Russell et al. 1999) oi the
Go/No-Go task (Ozonoff and McEvoy 1994). One study,
examining conict piocessing, found no gioup diffeiences
in mean ACC activation duiing functional magnetic ieso-
nance imaging (fMRI); howevei, the iesults indicated an
abnoimal time couise of the hemodynamic iesponse in
this iegion duiing conict conditions (Dichtei and Belgei
2007). Evidence also suggests abnoimal functional con-
nectivity between ACC and othei impoitant iegions in
ASD (Welchew et al. 2005; Kana et al. 2007). Abnoimal
behavioial peifoimance in conict piocessing, signifcant
metabolic ieduction in the ACC (Haznedai et al. 1997),
and abnoimal ACC activation and connectivity togethei
suggest a piominent iole of the ACC in impaiied execu-
tive contiol in ASD.
Recent iesults suggest that the thiee attentional net-
woiks communicate with and inuence one anothei to
suppoit the functional integiation and inteiaction of
attention (Fan et al. 2009). The oveifocused oi selective
attention found in individuals with autism (Lovaas et al.
1979) may ieect abnoimal inteiactions among atten-
tional netwoiks and coie defcits of executive contiol,
iathei than a naiiowed spotlight of visuospatial attention.
648 20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc.
AIIehIiohal NeIworks ih AuIism J. lan e| a|.
Most piioi studies on this topic weie conducted using
sepaiate tasks not designed to investigate inteiactions
among attentional netwoiks. Thus, inteiactions among
attentional netwoiks in individuals with ASD compaied
with healthy contiols (HCs) would seem to be a paiticu-
laily impoitant aiea of examination.
We examined the functions and neuial mechanisms of
the thiee attentional netwoiks in individuals with ASD
using the Attention Netwoik Test-Revised (ANT-R) (Fan
et al. 2009), piobing attentional functions and allowing
analysis of the functional integiation and inteiaction of
the attentional netwoiks. We hypothesized defcits in the
aleiting, oiienting, and executive contiol netwoiks, and
abnoimal inteiaction among these netwoiks in the ASD
gioup ielative to HCs.
Nethod
Participants
All eligible paiticipants undeiwent a diagnostic evaluation
consisting of psychiatiic, medical, and developmental
assessment (see Table 1 foi demogiaphic and clinical
data). Intelligence quotient (IQ) was measuied using the
Wechslei Adult Intelligence Scale, thiid edition
(WAIS-III) (Wechslei 1997). Fouiteen high-functioning
adults with autistic disoidei oi Aspeigei`s syndiome
(ASD gioup) and 14 healthy contiol (HC gioup) paitici-
pants weie ieciuited foi this study at the Seavei Autism
Centei foi Reseaich and Tieatment, Mount Sinai School
of Medicine (MSSM). HCs weie matched with patients
on aveiage IQ (within 15 points, 1 SD), age (biith date
within 24 months), gendei, and handedness. Handedness
scoies weie measuied by administeiing the Edinbuigh
Handedness Inventoiy (Oldfeld 1971). Paiticipants with
ASD weie diagnosed with autism oi Aspeigei`s syndiome
by psychiatiic inteiview accoiding to the Diagncstic and
Statistical Manual-IV Text Revision (DSM-IV-TR). These
diagnoses weie confimed by the Autism Diagnostic
Inteiview-Revised (ADI-R; Loid et al. 1994) and Autism
Diagnostic Obseivation Schedule-Geneiic (ADOS-G; Loid
et al. 2000), except foi one paiticipant foi whom ADI-R
was unavailable.
Exclusion ciiteiia included epilepsy, histoiy of schizo-
phienia, schizoaffective disoidei, oi othei Axis I mental
disoideis, except attention-defcit hypeiactivity disoidei
oi obsessive-compulsive disoidei (given the phenotypic
oveilap with ASD), and use of depot neuioleptic medica-
tion oi othei psychoactive diugs within the past 5 weeks.
We also excluded potential paiticipants with a lifetime
histoiy of substance/alcohol dependence and oi sub-
stance/alcohol abuse within the last yeai. Additional
exclusion ciiteiia included histoiy of encephalitis, phenyl-
ketonuiia, tubeious scleiosis, fiagile X syndiome, anoxia
duiing biith, neuiofbiomatosis, hypomelanosis of Ito,
hypothyioidism, Duchenne musculai dystiophy, and
mateinal iubella. Potential HCs weie excluded based on
medical illness oi histoiy in fist-degiee ielatives of devel-
opmental disoideis, leaining disabilities, autism, affective
disoideis, and anxiety disoideis.
Two ASD paiticipants and two HC paiticipants weie
excluded fiom the fnal sample due to indications fiom a
neuioiadiologist iepoit of abnoimal biain stiuctuie, low
(chance-level) accuiacy, motion gieatei than one voxel
size, oi technical issues iesulting in the absence of behav-
ioial data, with one paiticipant in each of these catego-
iies. The fnal sample foi this iepoit included 12 ASD
(eight with autism and foui with Aspeigei`s syndiome)
and 12 HC paiticipants. All paiticipants piovided wiitten
infoimed consent, appioved by the MSSM Institutional
Review Boaid.
Ihe Attention Network Iest - Revised
The ANT-R is a ievision of the oiiginal ANT (Fan et al.
2002) aimed at optimizing attentional contiasts, as
desciibed in oui pievious publication (Fan et al. 2009). A
minoi diffeience between the task used in the cuiient
fMRI study and oui pievious behavioial study (Fan et al.
2009) is that asteiisks, instead of ashing boxes, weie
TabIe 1. Demographic dala (means SD) ol ASD and HC groups.
Parlicipanl characlerislics
ASD
(n !2)
HC
(n !2) | |
Age (years) 30 6 28 7 0.85 0.4!
Sex (male/lemale) 9M/3l !0M/2l 0.49 0.62
Handedness score 69 37 75 47 0.34 0.74
Years ol educalion !5.6 2.2 !5.8 !.7 0.25 0.83
lull scale lQ !!5 !4 !20 !5 0.84 0.4!
Verbal lQ !!6 !7 !20 !5 0.75 0.46
Perlormance lQ !!2 !5 !!6 !! 0.65 0.52
ASD diagnosis (aulism/
Asperger)
8/4
ADl-P 38.4 !3.4
Social !8.8 8.0
Verbal communicalion !2.9 4.0
Pepelilive behavior 6.7 3.6
ADOS-C !2.2 4.!
Communicalion 3.0 !.8
Social 7.3 2.5
lmaginalion 0.8 0.7
Slereolyped behaviors !.3 !.3
ASD, aulism speclrum disorder, HC, heallhy conlrol, lQ, inlelligence
quolienl, ADl-P, Aulism Diagnoslic lnlerview-Pevised, ADOS-C, Aul-
ism Diagnoslic Observalion Schedule-Ceneric.
MannWhilney U lesl.
ADl-P scores were nol available lor one parlicipanl, lherelore n !!
lor lhis measure.
20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc. 649
J. lan e| a|. AIIehIiohal NeIworks ih AuIism
used in the cue conditions (see Fig. 1). The paiticipants`
task was to iespond to the diiection that the centei aiiow
(taiget) was pointing (eithei left oi iight) using the left
index fngei foi the left diiection and the iight index fngei
foi the iight diiection. The foui ankei aiiows, two on
the left and two on the iight side of the taiget, weie eithei
pointing to the same diiection as the taiget (congiuent
condition) oi the opposite diiection (incongiuent condi-
tion). The cue-to-taiget inteivals (0, 400, and 800 msec)
weie selected based on pievious studies with noimal
paiticipants and patients with paiietal damage (Posnei
et al. 1984; Fan et al. 2002). The ANT-R was compiled
and iun on a peisonal computei using E-Piime soft-
waie (Psychology Softwaie Tools, Pittsbuigh, PA).
The function of each of the thiee attentional netwoiks is
opeiationally defned as a compaiison of the peifoimance
(ieaction time oi accuiacy) between one condition and the
appiopiiate iefeience condition, iesulting in scoies foi the
attentional netwoiks (Fan et al. 2009). Foi the aleiting net-
woik, the phasic aleiting (beneft) effect is defned as follows:
Aleiting RT RT iepiesenting the beneft
of aleiting. Foi the oiienting netwoik, the validity includes
the ability to disengage attention fiom a pievious location
and to move and engage attention at a new location.
Coiiespondingly, oiienting opeiations aie defned as
follows: Validity Disengaging (Moving Engaging)
RT RT , which iepiesents both the cost
of an invalid cue and beneft of a valid cue. The validity effect
has two subcomponents, disengaging and moving/engaging:
(1) Disengaging RT RT foi the cost of
disengaging fiom invalid cue; (2) Moving Engaging
RT RT , foi the beneft of taiget
iesponse undei the valid cue condition. The Moving
Engaging is equivalent to the computation of oiienting"
defned in oui pievious study (Fan et al. 2002). In addition,
Oiienting time RT
RT is defned foi the beneft
of the taiget iesponse because of the advanced oiienting
undei the 800-msec cue-taiget inteival condition. The
conict effect, which is a cost, is defned as follows: Flankei
conict RT RT . We have
pieviously shown that the location incongiuency effect
(whethei the location of the taiget left oi iight is on the
same side as the taiget is pointing) is veiy small (Fan et al.
2009), and thus, we did not examine this effect- oi location-
ielated inteiactions in this study.
The inteiaction effects aie defned as follows: (1) Aleiting
by ankei conict (RT RT
) (RT RT
). A negative value indicates a negative
no cue double cue spatial cue
+
+
+
valid
invalid
+
Flanker: congruent
Location: congruent
Flanker: incongruent
Location: congruent
Flanker: congruent
Location: incongruent
Flanker: incongruent
Location: incongruent
Target
Cue

figure 1. The schemalic ol lhe Allenlion Nelwork Tesl-Pevised (ANT-P). ln each lrial, depending on lhe cue condilion (none, double, and valid
or invalid cues), an aslerisk "" as lhe cue appears lor !00 msec. Aller a variable duralion (0, 400, or 800 msec), lhe largel (lhe cenler arrow)
and lwo lanker arrows on lhe lell and righl side (congruenl or incongruenl lankers) are presenled lor 500 msec. The parlicipanl makes a
response lo lhe largel's direclion. The posl-largel lxalion period jillers belween 2000 and !2,000 msec.
650 20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc.
AIIehIiohal NeIworks ih AuIism J. lan e| a|.
impact of aleiting on ankei conict piocessing. (2) Oiient-
ing by ankei conict (RT
RT ) (RT
RT ). A positive value indicates moie
effcient conict piocessing because of valid oiienting. (3)
Validity by ankei conict (RT
RT ) (RT
RT ). A positive value indicates less
effcient ankei conict piocessing because of invalid
oiienting. The effects in eiioi iate follow the same
foimulas.
Event-related fNRl
Event-ielated fMRI was used to study the activation of the
attentional netwoiks. The time inteival between the onset
of the taiget and the next tiial was jitteied. The duiation
between the offset of the taiget and the onset of the next
tiial was vaiied systematically with a set of 12 disciete times
fiom 2000 to 12,000 msec, including 10 inteivals fiom
2000 to 4250 msec with an inciease step of 250-, 4750-,
and 12,000-msec inteivals, appioximating an exponential
distiibution with a mean of 4000 msec. The mean tiial
duiation was 5000 msec. The iesponse collection window
was 1700 msec fiom onset of the taiget and the ankeis.
Theie weie foui iuns in this expeiiment with 72 test tiials
in each. The total duiation foi each iun was 420 sec. Total
time iequiied to complete this task was about 30 min.
Data acquisition and analysis
Stimuli weie piesented at the centei of the paiticipant`s
feld of view thiough a supei video giaphics aiiay liquid
ciystal display piojectoi system onto a ieai-piojection
scieen mounted at the back of the magnet boie. Paitici-
pants viewed stimuli via a miiioi attached to the head coil
and positioned above theii eyes. Paiticipants iesponded
with both hands using the BiainLogics fbei optic button
system (Psychology Softwaie Tools, Pittsbuigh, PA).
Laboiatoiy testing and tiaining occuiied outside of the
scannei piioi to the scan. In the scannei, paiticipants
viewed the stimuli and piovided iesponses, iecoided via
computei, as measuies of ieaction time and accuiacy.
Mean RTs undei the cue-by-taiget conditions weie calcu-
lated aftei excluding the eiioi tiials. Eiioi iates undei
each of these conditions weie also calculated. Because
behavioial data often have nonnoimal distiibutions,
skewness and kuitosis statistics weie examined indepen-
dently foi each gioup foi each vaiiable. Any vaiiable that
exhibited both a skewness and kuitosis value gieatei than
1 was subject to nonpaiametiic analysis, using the Mann
Whitney U statistic. All othei between-gioup analyses
weie examined using paiametiic statistics.
Image acquisition
All MRI acquisitions weie obtained on a 3 T Siemens
Allegia MRI system at Mount Sinai School of Medicine.
Each scanning iun staited with two dummy volumes
befoie the onset of the task to allow foi equilibiation of
T1 satuiation effects, followed by 168 image volumes. All
images weie acquiied along axial planes paiallel to the
anteiioi commissuieposteiioi commissuie (ACPC) line.
A high-iesolution T2-weighted anatomical volume of the
whole biain was acquiied on an axial plane paiallel to the
ACPC line with a tuibo spin-echo pulse sequence with
the following paiameteis: 40 axial slices 4-mm thick,
skip 0 mm, iepetition time (TR) 4050 msec, echo
time (TE) 99 msec, ip angle 170, feld of view
(FOV) 240 mm, matiix size 448 512, voxel
size 0.47 0.47 4 mm. Foui iuns of T2-weighted
images weie acquiied with a giadient echo-planai imag-
ing sequence using the following paiameteis: 40 axial
slices 4-mm thick and skip 0 mm, TR 2500 msec,
TE 27 msec, ip angle 82, FOV 240 mm, matiix
size 64 64.
Image anaIysis
Event-ielated analyses of the functional imaging data
fiom the ANT-R sessions weie conducted using statistical
paiametiic mapping (SPM2; Wellcome Tiust Centie foi
Neuioimaging, London, UK). The functional scans weie
iealigned to the fist volume, coiegisteied with the
T2-weighted anatomical image, noimalized to a standaid
template (MNI: Montieal Neuiological Institute), iesam-
pled to 2 2 2 mm , and spatially smoothed with an
8 8 8-mm full-width-at-half-maximum Gaussian
keinel. Event-ielated analyses weie peifoimed using the
default SPM basis function, which consists of a synthetic
hemodynamic iesponse function (HRF) composed of two
gamma functions.
Geneial lineai modeling was conducted foi the func-
tional scans fiom each paiticipant by modeling the mea-
suied event-ielated blood oxygen leveldependent
(BOLD) signals and iegiessois to identify the ielation-
ship between the expeiimental events (i.e., the vaiious
manipulations in the ANT-R) and the hemodynamic
iesponse. Regiessois weie cieated by convolving a tiain
of delta functions iepiesenting the sequence of individual
events with the SPM basis function. The iegiessois
included fve cue-ielated HRFs: double cue, left valid cue,
iight valid cue, left invalid cue, iight invalid cue; and 16
taiget-ielated HRFs: foui cue conditions (no cue, double
cue, valid cue, invalid cue) two ankei conditions
(congiuent and incongiuent) two taiget locations (left
and iight). The six paiameteis geneiated duiing motion
20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc. 651
J. lan e| a|. AIIehIiohal NeIworks ih AuIism
coiiection weie enteied as covaiiates. The specifc effects
of attentional piocesses weie tested by applying lineai
contiasts to the iegiessois, such that foi the conict effect,
the contiast of incongiuent (eight iegiessois) minus con-
giuent (eight iegiessois) conditions was used. The taiget
iesponses undei diffeient cue-by-taiget conditions weie
equally weighted foi the contiast between congiuent and
incongiuent conditions. Foi fMRI analysis, the following
attentional netwoik effects weie defned diffeiently. Foi
the aleiting effect, the contiast was defned as double
cue vs. baseline. Moving engaging was ipped as valid
cue minus double cue. In addition, oiienting was defned
as spatial cue (valid invalid) minus double cue.
The images of contiast estimates fiom all paiticipants
weie enteied into a second-level gioup analysis conducted
with a iandom-effect statistical model. An uncoiiected P-
value of 0.01 foi the height (intensity) thieshold of each
activated voxel and an uncoiiected P-value of 0.05 foi
extent thieshold weie simultaneously applied. This height
and extent thieshold combination is similai to the thiesh-
old suggested to ieach a desiiable balance between Type I
and Type II eiiois (Liebeiman and Cunningham 2009).
The iesultant statistical maps thiesholded foi height and
extent piotect against an ination of the false-positive
iate. Piioi Monte Cailo simulations confim the piesent
voxel contiguity thieshold (see Fan et al. 2011).
Foi the iegion-of-inteiest (ROI) analysis, we extiacted
the iegiession coeffcients ( values) fiom the incongiu-
ent minus congiuent contiast using a spheie with a
6-mm iadius centeied on the voxel of local maxima,
identifed based on gioup diffeiences. The values of
ROIs aie independent fiom the measuies of RT and accu-
iacy in the iegiession analyses. We examined between-
gioup diffeiences in the slope (which is independent of
the main effect of gioup diffeience) of the iegiession
models of the conict effects (in eiioi iate and RT) as a
function of the biain activity ielated to conict piocessing
(contiast between incongiuent and congiuent conditions)
at the gioup level. In this analysis, behavioial conict effects
weie dependent vaiiables, with ACC activation (extiacted
fiom the ROI peak 2, 34, 24]), gioup, and the inteiac-
tion teim of ACC activation-by-gioup vaiiables as piedic-
tois. To exploie whethei the defcits in conict piocessing
aie associated with clinical symptoms, we also conducted
coiielation analyses on the ielationship between the mea-
suies of neuional and behavioial effects, and the ADI-R
and ADOS-G diagnostic algoiithm total iaw scoies and
subscale scoies. An uncoiiected P-value of 0.01 was used.
Due to pieexisting gioup diffeiences in eiioi iates (and
potential ielated ACC activation), eiioi tiials weie
modeled neithei at the individual level noi as a covaiiate
at the gioup level to avoid specifcation eiioi, an inappio-
piiate use of analysis of covaiiance to deal with substantive
gioup diffeiences on potential covaiiates (Millei and
Chapman 2001). Given the laige liteiatuie on cognitive
defcits in ASD, incieased conict effect in eiioi iate is not
viewed as a covaiiate but iathei as a featuie of the disoidei.
Results
Differences in behavioral performance
One sample t-tests with both gioups combined showed
that the attentional effects (in RT) of aleiting, validity, dis-
engaging, moving engaging, oiienting time, and ankei
conict weie signifcant (P 0.01). The validity by ankei
was also signifcant (P 0.05), although aleiting by
ankei effect was not signifcant (P 0.05). Foi the eiioi
iate, the effects of aleiting (P 0.05), validity (P 0.01),
disengaging (P 0.01), oiienting time and ankei conict
(P 0.01), and validity by ankei (P 0.05) weie signif-
cant, but moving engaging, aleiting by ankei, and
oiienting by ankei weie not signifcant.
Compaiing the two gioups, the mean oveiall accuiacy
foi HC and ASD gioups was 92 6 and 79 12%
(mean and standaid deviation), iespectively; mean ovei-
all RTs foi these two gioups weie 883 161 and
878 164 msec, iespectively. The ASD gioup made sig-
nifcantly moie eiiois than the HC gioup (13% diffei-
ence), t 3.26, P 0.01, but the diffeience in oveiall
RT (6 msec) was not signifcant, t 0.09, P 0.05.
Figuie 2 shows the netwoik scoies in RT and eiioi iate,
iespectively. Although theie weie no signifcant gioup
diffeiences in RT, nonpaiametiic statistical analyses
showed a signifcant gioup diffeience in aleiting-ielated
eiiois, MannWhitney U 34.5, n n 12, P 0.05.
The ASD gioup (M 4.4%, MDN 4.3%) made signif-
icantly moie eiiois than the HC gioup (M 1.0%,
MDN 0.0%) when the taiget appeaied without, com-
paied with, an aleiting cue. The conict effects foi HC
and ASD in eiioi iate weie 6 4 and 18 15%
(gieatei vaiiance in ASD), iespectively, and in RT weie
132 52 and 151 72 msec, iespectively. The ASD
gioup made signifcantly moie eiiois than the HC
gioup (18.1 vs. 5.9%) undei the incongiuent compaied
with the congiuent taiget condition, t 2.76,
P 0.05.
Differences in functional activation
associated with the attentional processes
Figuie 3 and Table 2 show diffeiences in biain activation
between HC and ASD gioups (HC ASD) ielated to
each of the thiee attentional piocesses; HC exhibited
gieatei activation acioss all contiasts. Foi the aleiting
effect, the left MFG (Fig. 3A), caudate nucleus, and iight
652 20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc.
AIIehIiohal NeIworks ih AuIism J. lan e| a|.
MFG weie signifcantly diffeient. Foi the validity effect,
mid/posteiioi cingulate coitex and piegenual ACC
(Fig. 3B) in the fiontopaiietocingulate netwoik weie
signifcantly diffeient. Fuithei paitition of the validity
effect into its two subcomponents, disengaging and mov-
ing/engaging, showed that the left and iight piegenual
ACC (Fig. 3C), iight supiamaiginal gyius and infeiioi
paiietal lobule (IPL a subdivision of TPJ), and angulai
gyius weie signifcantly diffeient duiing disengaging, and
that the fusifoim gyius (Fig. 3D), supeiioi tempoial
gyius, and anteiioi insulai coitex weie signifcantly diffei-
ent duiing moving/engaging. Oiienting showed similai
gioup diffeiences (Fig. 3E) to the moving/engaging effect.
The conict effect showed focal diffeiences in ACC acti-
vation (Fig. 3F).
Inteiactions showed similai patteins to main effects. The
aleiting by ankei conict effect was associated with gieatei
activation in the iight supeiioi fiontal gyius (Fig. 3G); the
oiienting by ankei conict effect was associated with
gieatei activation in the IPS (Fig. 3H), mid-occipital gyius,
and ceiebellai veimis; the validity by ankei conict effect
was associated with gieatei ACC activation (Fig. 3I).
Further analysis of conHict processing and
the executive control network
We hypothesized that executive contiol netwoik abnoi-
mality in ASD was associated with defcits in the thiee
domains of ASD. Theiefoie, we fuithei examined patteins
of gioup diffeiences in conict piocessing. Regions of the
fiontopaiietal contiol netwoik and the anteiioi insulai
coitex weie activated in both gioups (Fig. 4A and B,
Tables 3 and 4). HC had gieatei activation than ASD
only in the ACC (as in Fig. 3F and Table 2), with no sig-
nifcant activation in the ACC foi conict piocessing in
the ASD gioup. Theie was also no clustei showing signif-
cantly gieatei activation foi the contiast of ASD minus
HC. In addition, the ACC clustei of gioup diffeiences
extended to the posteiioi cingulate coitex, which was due
to gieatei deactivation in the ASD gioup. We also exam-
ined the possibility of a gioup (ASD, HC) by ankei con-
giuency (congiuent, incongiuent) inteiaction by
extiacting peiimetei estimates ( value) fiom the ACC.
The HC gioup showed less deactivation foi the incongiu-
ent condition than the congiuent condition, iesulting in a
positive conict effect. Howevei, the ASD gioup showed
gieatei activation foi the congiuent compaied with the
incongiuent conditions, iesulting in a negative (oi lack
of) conict effect.
Analysis of vaiiance foi the behavioial data was con-
ducted with gioup (HC, ASD) as a between-subject factoi
and congiuence (congiuent, incongiuent) as a within-
subject factoi. Theie was a signifcant main effect of con-
ict on eiioi iate (F 29.63, P 0.01); eiioi iate
undei the incongiuent condition was signifcantly highei
than undei the congiuent condition. Theie was also a sig-
nifcant gioup diffeience on oveiall eiioi iate
(F 10.49, P 0.01). In addition, the conict by
gioup inteiaction was signifcant (F 7.62,
P 0.01); the conict effect was signifcantly gieatei in
the ASD gioup than in the HC gioup. Foi RT, although
the main conict effect was signifcant (F 121.88,
P 0.01), the gioup diffeience was not signifcant
(B)
(A)
-50
0
50
100
150
200
Measurements
HC
ASD
-5
0
5
10
15
20
25
Measurements
HC
ASD
figure 2. 8ehavioral perlormances measured by reaclion lime (PT)
(A) and error rale (8) lor each measuremenl lor lhe groups ol heallhy
conlrols (HC) and individuals wilh aulism speclrum disorders
(ASD). Lrror bars represenl lhe slandard error lor each measuremenl.
Nole. *p < 0.05
20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc. 653
J. lan e| a|. AIIehIiohal NeIworks ih AuIism
(F 1) and the conict by gioup inteiaction was not sig-
nifcant (F 1) (see Fig. 4C and D).
The conict effect in eiioi iate can be piedicted by the
conict-ielated ACC activation (r 0.56, F 9.81,
P 0.01). To examine whethei the ielation of conict-
ielated ACC activity and eiioi iate between gioups weie
paiallel, the conict effect in eiioi iate was iegiessed on
ACC activation, gioup, and ACC activation-by-gioup
vaiiables. The inteiaction teim was signifcant (t 3.16,
P 0.01), indicating that the slopes weie not paiallel.
Fuithei examination of the ielation between conict-
ielated ACC activity and eiioi iate by gioup showed a
signifcant coiielation in the ASD gioup (r 0.66, F
7.80, P 0.05), but not in the HC gioup (r 0.26,
F 1). These iesults suggest that an incieased cost of
conict (in eiioi iate) is coiielated with decieases in
ACC activation in the ASD gioup, but no signifcant iela-
tion in the HC gioup (see Fig. 4E).
Similai to eiioi iate, the conict effect in RT can be
piedicted by conict-ielated ACC activation (r 0.46,
F 6.04, P 0.05) in both gioups. Moie effcient
conict piocessing (less inciease in RT undei the incon-
giuent condition compaied with the congiuent condition)
was ielated to gieatei ACC activation. The inteiaction
teim in a model testing the paiallelism of the two slopes
with conict-ielated ACC activation, gioup, and conict-
ielated ACC activation-by-gioup inteiaction as piedictois
showed that the inteiaction teim was not signifcant
(t 0.23, P 0.05). This indicates that the conict-
ielated ACC activation does not diffeientially piedict the
conict effect in RT between gioups (see Fig. 4F). ACC
activity was ielated to the conict effect measuied by RT
in both gioups.
The ielation between functional activation duiing the
conict piocessing of the ROI, which was identifed by
gioup diffeience, the behavioial effect of conict, and
ADI-R subscoies in ASD gioup was also examined. Results
indicate that the communication and language domain
was signifcantly coiielated with the effciency (measuied
as accuiacy) duiing conict piocessing (Fig. 5). That is,
domain symptoms in communication and language aie
ielated to less effcient conict piocessing.
(A)
(E) (D)
(C) (B)
Alerting Validity Disengaging
Moving + Engaging Orienting
(F)
(G)
Conflict
Alerting x Flanker Conflict Orienting x Flanker Conflict Validity x Flanker Conflict
(I) (H)
figure 3. Dillerences (heallhy conlrols HC grealer lhan individuals wilh aulism speclrum disorders ASD) in brain aclivalion corresponding lo
lhe measures ol nelwork ellecls. The color was scaled lrom | 2.5! lo 5 lor lhese group dillerence maps.
654 20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc.
AIIehIiohal NeIworks ih AuIism J. lan e| a|.
Discussion
Oui iesults indicate signifcant behavioial defcits of the
aleiting and executive attentional netwoiks in ASD iela-
tive to HC, but not the oiienting netwoik oi netwoik
inteiactions. Behavioial defcits weie associated with
abnoimalities in the neuial netwoiks suppoiting atten-
tional functions. Even in the absence of behavioial diffei-
ences among the oiienting netwoik and netwoik
inteiactions, neuial diffeiences weie piesent.
Individuals with ASD made moie eiiois if theie was
no aleiting cue pieceding the taiget. This aleiting defcit
was associated with abnoimal activation of MFG and cau-
date nucleus in ASD. The ieduced activation of MFG and
caudate nucleus may suggest a defciency of using these
biain aieas foi the aleiting iesponse to unanticipated tai-
gets in ASD. Defcits in these biain netwoiks may undei-
pin the abnoimal aleiting behavioi identifed in the
piesent and pievious studies (e.g., Pascualvaca et al.
1998). It is woith noting that unlike piioi studies (Daw-
son et al. 1998; Landiy and Biyson 2004; Tedei-Salejaivi
TabIe 2. Crealer nelwork-relaled aclivalion in HC compared wilh
individuals wilh ASD.
Pegion
L /
P 8A
MNl coordinales
Z | x y z
Alerling
Mid-lronlal gyrus L 9 38 36 28 4.63 650
Mid-lronlal gyrus L 46 36 28 40 4.!4
Mid-lronlal gyrus L 9 46 !6 44 3.20
Caudale nucleus P 6 6 2 4.30 488
Caudale nucleus L !2 !8 !4 3.70
Medial/orbilal lronlal
gyrus
P !! !2 48 !2 3.98 !82
Medial/orbilal lronlal
gyrus
P !! !2 22 8 3.34
Medial/orbilal lronlal
gyrus
P !! !8 34 !4 2.73
Validily
Mid-lronlal gyrus L 9 36 44 !4 4.75 344
Mid-lronlal gyrus L !0 24 46 4 3.02
lnlerior parielal lobule L 40 46 52 48 3.74 !88
Superior lronlal gyrus P 9 22 52 26 3.55 238
Mid-lronlal gyrus P !0 26 44 20 3.39
Anlerior cingulale
corlex
L 24 0 36 26 3.52 627
Anlerior cingulale
corlex
P 24 4 34 !2 3.49
Anlerior cingulale
corlex
L 32 8 36 22 3.33
lnlerior parielal lobule P 40 48 46 48 3.25 458
Supramarginal gyrus P 40 54 46 38 3.24
lnlerior parielal lobule P 39 52 54 40 3.02
Mid-cingulale corlex P 23 8 !6 38 3.24 26!
Mid-cingulale corlex L 23 0 !4 38 3.22
Mid-cingulale corlex P 24 4 2 38 3.!9
Moving Lngaging
lusilorm gyrus L 37 34 38 !0 3.92 509
lusilorm gyrus L !9 38 70 8 3.8!
lusilorm gyrus L 37 26 40 !2 3.76
Superior lemporal
gyrus
P 38 32 8 30 3.48 !67
Anlerior insular corlex P 32 !6 !8 3.!7
Disengaging
Anlerior cingulale
corlex
L 24 6 30 !8 3.!0 480
Anlerior cingulale
corlex
L 24 2 34 !0 3.05
Anlerior cingulale
corlex
P 32 !0 40 8 2.99
Supramarginal gyrus P 40 48 40 36 2.84 30!
lnlerior parielal lobule P 40 46 46 44 2.80
Angular gyrus P 40 56 50 30 2.73
Orienling
lusilorm gyrus L 37 26 24 20 3.70 286
lusilorm gyrus L 37 34 38 !0 3.63
Anlerior insular corlex P 30 8 !4 3.47 2!3
P 32 8 28 3.28
(Con||nued)
TabIe 2. Conlinued.
Pegion
L /
P 8A
MNl coordinales
Z | x y z
Superior lemporal
gyrus
llanker conlicl
Anlerior cingulale
corlex
L 32 2 34 24 3.9! !!0!
Anlerior cingulale
corlex
L 24 0 28 32 3.68
Anlerior cingulale
corlex
P 24 2 2 36 3.30
Alerling by lank conlicl
Superior lronlal gyrus P 9 20 50 !4 4.36 220
Orienling by lanker conlicl
lnlerior parielal lobule L !9 32 60 30 3.7! 244
Mid-occipilal gyrus L 39 38 68 28 3.29
Cerebellum (vermis) L 6 74 !8 3.58 !93
Validily by lanker conlicl
Anlerior cingulale
gyrus
P 32 4 !4 46 2.92 !57
Anlerior cingulale
gyrus
L 32 6 !6 40 2.82
ASD, aulism speclrum disorder, HC, heallhy conlrol, 8A, 8rodmann
area, L/P, lell/righl, MNl, Monlreal Neurological lnslilule.
There was no clusler showing signilcanl grealer aclivalion lor lhe
conlrasl ol ASD minus HC.
The conlrasl ol HC minus ASD lor validily showed cerebellum acliva-
lion (x !8, y 56, z 26, Z 3.58, | 209).
The conlrasl ol HC minus ASD lor Moving Lngaging showed lell
mid-lronlal gyrus aclivalion (8rodmann area 9, x 38, y 28,
z 38, Z 3.95, | 235).
Lxlends lo lhe poslerior cingulale corlex.
20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc. 655
J. lan e| a|. AIIehIiohal NeIworks ih AuIism
et al. 2005), we did not fnd signifcant gioup diffeiences
in behavioial effects of oiienting.
Foi oiienting, while behavioi was similai between
gioups, diffeiences in the neuiophysiological data deseive
fuithei discussion. Gieatei activation foi the validity
effect (and subcomponents of disengaging and moving/
engaging in key iegions of the default-mode netwoik
(DMN) (mid/posteiioi cingulate coitex, and piegenual
ACC, supeiioi tempoial gyius, and angulai gyius) as well
as in iegions of the task-positive netwoik (TPN) (anteiioi
insulai coitex, TPJ, IPL, and fusifoim gyius) foi the
HC ASD contiast may indicate moie task-ielated effoit
(decieased DMN, incieased TPN) in the ASD gioup. This
gieatei task-ielated effoit could imply a foim of compen-
sation foi behavioial peifoimance in oiienting. Inconsis-
tencies in oiienting defcits may be attiibutable to at least
two majoi factois: (1) ceiebellai and/oi paiietal abnoi-
malities, not piesent in ASD patients in the piesent sam-
ple, aie a likely contiibutoi to oiienting defcits
(Townsend et al. 1996a); (2) iecent evidence suggests that
D S A C H
0
10
20
30
40
50
-1 -0.5 0 0.5 1 1.5
Conflict effect on ACC activation (beta)
ASD
HC
0
100
200
300
-1 -0.5 0 0.5 1 1.5
Conflict effect on ACC activation (beta)
ASD
HC
Congruent
Incongruent
Congruent
Incongruent
0
5
10
15
20
25
30
35
40
HC ASD HC ASD
Group
0
200
400
600
800
1000
1200
Group
(A) (B)
(C) (D)
(E) (F)
figure 4. 8rain aclivalion associaled wilh lanker conlicl ellecl in
heallhy conlrols (HC) (A) and individuals wilh aulism speclrum
disorders (ASD) (8) during lhe allenlion nelwork lesl. The color was
scaled lrom | 2.5! lo 5 lor individual group maps. 8ehavioral
perlormances measured by error rale (C) and reaclion lime (PT) (D)
under congruenl and incongruenl condilions lor lhe HC and ASD
groups. Lrror bars represenl lhe slandard error under each condilion,
analyses ol equalily ol lhe linear relalionship belween conlicl ellecls
in error rale and ACC aclivalion (L), and belween conlicl ellecls in
PT and ACC aclivalion (l), in HC and ASD groups.
TabIe 3. Conlicl-relaled aclivalion in heallhy conlrols.
Pegion
L /
P 8A
MNl coordinales
Z r x y z
lnlerior parielal lobule P 7 26 48 52 5.07 !679
Superior parielal lobule P 7 22 62 58 4.29
lnlerior parielal lobule P 40 36 40 52 4.!5
lnlerior lronlal/
orbilolronlal gyrus
P 47 50 20 4 4.73 6!!
Anlerior insular corlex P 34 26 0 2.99
lnlerior lronlal/
orbilolronlal gyrus
P 47 36 24 !2 2.78
lnlerior occipilal gyrus L !9 42 68 !2 4.6! 98!
Cerebellum (Crus !) L 36 62 28 3.75
lnlerior occipilal gyrus L 44 82 4 3.73
Superior occipilal gyrus P !9 36 76 8 4.!9 !95
Mid-occipilal gyrus P !8 34 84 6 3.65
lnlerior occipilal gyrus P !9 38 84 4 3.39
Anlerior insular corlex L 34 !8 !0 3.89 603
Anlerior insular corlex L 42 !6 6 3.89
Anlerior insular corlex L 34 22 2 3.22
Anlerior cingulale
corlex
P 32 4 !6 46 3.89 !084
Anlerior cingulale
corlex
P 24 4 22 34 3.63
Supplemenlary molor
area
L 6 8 2 52 3.29
Precenlral gyrus L 6 30 !0 52 3.74 363
Precenlral gyrus L 6 26 6 46 3.56
Precenlral gyrus L 6 34 8 42 2.94
Superior lronlal gyrus P 6 26 0 52 3.66 329
Precenlral gyrus P 6 44 0 44 2.99
Precenlral gyrus P 6 40 2 52 2.6!
Mid-occipilal gyrus P !9 30 66 34 3.65 !89
Mid-lronlal gyrus P 46 28 48 !6 3.4! 25!
Mid-lronlal gyrus P 46 30 52 26 3.38
Superior parielal lobule L 7 26 50 52 3.37 404
Precuneus L 5 !0 56 58 3.35
Superior parielal lobule L 7 24 44 46 3.!6
lnlerior lronlal gyrus P 44 54 !4 32 3.!9 2!8
lnlerior lronlal gyrus P 45 48 24 22 3.07
Precenlral gyrus P 6 44 2 34 2.73
Poslcenlral gyrus L 2 38 34 42 3.!0 !89
Poslcenlral gyrus L 2 36 38 58 2.92
L/P, lell/righl, 8A, 8rodmann area, MNl, Monlreal Neurological lnsli-
lule.
Area along and near lhe inlraparielal sulcus.
lronloinsular corlex clusler.
lronlal eye lelds.
656 20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc.
AIIehIiohal NeIworks ih AuIism J. lan e| a|.
oiienting defcits in ASD may be moie ielated to social
than nonsocial cues (Gieene et al. 2011), a factoi that
could explain the lack of oiienting defcits in this study
(nonsocial cues weie used), as well as inconsistencies in
the liteiatuie.
Oui iesults also show signifcant behavioial defcits of
the executive contiol netwoik in ASD ielative to HC. Sig-
nifcant gioup diffeiences in conict piocessing of execu-
tive contiol weie associated with, as hypothesized,
abnoimal ACC activation in ASD. Howevei, unlike pievi-
ous studies, we found an absence of ACC activation
iathei than hypoactivation. In addition, highei eiioi iates
weie associated with the lack of activation in the ACC in
ASD. That is, dysfunction of the ACC iesulted in a highei
eiioi iate. Conict-ielated ACC activation was negatively
coiielated with the conict effect measuied in RT, sug-
gesting that ACC activation is ielated to effciency of
iesolving conict. Fuitheimoie, incieased numbei of
symptoms in the domain of communication and language
was ielated to less effcient conict piocessing. Oveiall,
these iesults indicate both behavioial and neuial abnoi-
malities in the executive contiol of attention in ASD and
a diiect association with symptom domains in ASD.
The signifcant ACC defcit duiing conict piocessing
may iepiesent a fundamental defcit in ASD. This study
shows abnoimal (in fact, absent) ACC activation in ASD
ielative to HC in the anteiioi iostial cingulate zone
(RCZa), a cognitive" iegion of the ACC. Reduced
metabolism (Haznedai et al. 1997) and ieduced fiac-
tional anisotiopy in white mattei undeilying the ACC
(indicating abnoimal miciostiuctuial integiity of the
white mattei) in ASD (Thakkai et al. 2008), and new
evidence fiom oui iecent magnetic iesonance spectios-
copy study of the attentional netwoiks in ASD showing
lowei glutamate/glutamine concentiation in the iight
ACC (Beinaidi et al. 2011), may explain this absence of
ACC activation duiing conict piocessing. Pievious stud-
ies on ASD have also shown hypoactivation in the RCZa
foi conict piocessing to iesponse shifts (Shafiitz et al.
2008), socialcognitive stimuli (Dichtei and Belgei 2007)
and iesponse inhibition (Kana et al. 2007), and ieduced
disciimination between eiiois and coiiect iesponses in a
subiegion defned as an affective division of the ACC
(Bush et al. 2000). Highei eiioi iates aie typically ielated
to gieatei ACC activation foi conict monitoiing. While
we found a negative coiielation between ACC activation
and eiioi iates in the ASD gioup, theie was no such
coiielation in the HC gioup. We speculate that
decieased ACC activity is associated with low awaieness
(which is also associated with moie eiiois), paiticulaily
in individuals with ASD.
The ACC, coupled with othei biain aieas such as the
anteiioi insulai coitex, plays a majoi iole in executive
contiol of attention (Bush et al. 2000; Posnei and Fan
2008), iesponse selection, piepaiation, execution (Fiith
et al. 1991), and emotion (Bush et al. 2000). Lack of con-
tiol may lead to defcits in iecipiocal social inteiaction,
communication and language, and iepetitive, steieotyped
activity, as well as othei behaviois commonly associated
with autism. The cuiient fnding of an intact fiontopaii-
etal netwoik in conict piocessing in ASD distinguishes
the ACC fiom the fiontopaiietal netwoik, consistent with
iecent woik by othei gioups (e.g., Dosenbach et al. 2008).
It has been suggested that the ACC is involved in iapid
infoimation piocessing, wheieas the fiontopaiietal
TabIe 4. Conlicl-relaled aclivalion in individuals wilh ASD.
Pegion
L /
P 8A
MNl coordinales
Z r x y z
Anlerior insular corlex P 32 !6 4 4.59 807
lnlerior lronlal/
orbilolronlal gyrus
P 47 42 22 !2 3.4!
Mid-occipilal gyrus P !9 34 84 2 3.83 !77
lnlerior lronlal gyrus P 44 52 !0 30 3.63 400
lnlerior lronlal gyrus P 44 38 8 32 3.05
lnlerior lronlal gyrus P 44 46 26 30 2.95
Mid-occipilal gyrus L !9 24 64 32 3.6! !063
Superior parielal lobule L 7 28 52 58 3.40
lnlerior parielal lobule L 40 32 52 42 3.37
Anlerior insular corlex L 32 26 2 3.37 !87
Anlerior insular corlex L 32 !6 8 3.!4
lnlerior parielal lobule P 40 32 50 44 3.!0 788
lnlerior parielal lobule P !9 30 62 32 3.09
Superior parielal lobule P 7 30 62 58 2.84
Precenlral gyrus L 6 44 0 26 3.06 !45
Precenlral gyrus L 44 50 6 32 2.80
ASD, aulism speclrum disorder, L/P, lell/righl, 8A, 8rodmann area,
MNl, Monlreal Neurological lnslilule.
Area along and near lhe inlraparielal sulcus.
lronloinsular corlex clusler.
0
5
10
15
20
25
0 10 20 30 40 50
Conflict effect in error rate (%)
R = 0.56
2
figure 5. Symplom-execulive conlrol associalion. More symploms ol
communicalion/language are relaled lo grealer cosl on accuracy in
conlicl processing.
20!2 The Aulhors. bra|n and behav|or published by Wiley Periodicals, lnc. 657
J. lan e| a|. AIIehIiohal NeIworks ih AuIism
netwoik undeipins moie delibeiate, adaptive contiol (Gaiavan
et al. 2002; Kana et al. 2007; Dosenbach et al. 2008). Def-
cits in attentional domains may manifest when theie is a
iequiiement foi iapid executive contiol duiing conditions
involving high demands on infoimation piocessing.
Although alteiations in ACC activity aie not specifc to
ASD, the heteiogeneity of autistic symptoms may be
ielated to ASD-specifc abnoimalities in stiuctuial and
functional connectivity of the ACC with othei biain
stiuctuies and netwoiks inteiacting with diffeient cogni-
tive domains. One iecent study has shown that ASD is
associated with defcits in the fiontopaiietal netwoik,
ielated to executive contiol (Solomon et al. 2009). How-
evei, cuiient iesults indicate that the defcit is moie local-
ized; between-gioup diffeiences in othei iegions such as
the fiontopaiietal netwoik and the anteiioi insulai coitex
weie not signifcant. Fuithei examination of the piesent
attentional netwoik defcits in ASD ielative to othei neu-
iodevelopmental and psychiatiic disoideis will be neces-
saiy to test the specifcity of the piesent patteins.
Although defcits in the MFG and caudate aie tentative,
given few studies specifcally examining these iegions
ielating to aleiting, the ACC abnoimality may constitute
a fundamental defcit which is ielated to othei cognitive
domains. Knowledge of defcits in aleiting and executive
contiol could be used to facilitate new adjunctive intei-
ventions foi individuals with ASD, thus satisfying an
impoitant initiative to develop ASD-specifc neuiobehav-
ioial domains.
Acknowledgments
We thank Michael I. Posnei foi making insightful com-
ments, Jack M. Goiman foi his kind help, and Cheuk
Y. TangandKevinG. Guise foi assistance withdatacollection.
ConHict of lnterest
None declaied.
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