Eye-voice span during rapid automatized naming: evidence of reduced automaticity in individuals with autism spectrum disorder and their siblings

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1 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 RESEARCH Open Access Eye-voice spn during rpid utomtized nming: evidence of reduced utomticity in individuls with utism spectrum disorder nd their silings Aigil L Hogn-Brown 1, Renske S Hoedemker 2, Peter C Gordon 2 nd Molly Losh 1* Astrct Bckground: Individuls with utism spectrum disorder (ASD) nd their prents demonstrte impired performnce in rpid utomtized nming (RAN), tsk tht recruits vriety of linguistic nd executive processes. Though the sic processes tht contriute to RAN differences remin uncler, eye-voice reltionships, s mesured through eye trcking, cn provide insight into cognitive nd perceptul processes contriuting to RAN performnce. For exmple, in RAN, eye-voice spn (EVS), the distnce hed the eyes re when rticultion of trget item's lel egins, is n indirect mesure of utomticity of the processes underlying RAN. The primry ojective of this study ws to investigte utomticity in nming processes, s indexed y EVS during RAN. The secondry ojective ws to chrcterize RAN difficulties in individuls with ASD nd their silings. Methods: Prticipnts (ged yers) included 21 individuls with ASD, 23 silings of individuls with ASD, nd 24 control sujects, group-mtched on chronologicl ge. Nming time, frequency of errors, nd EVS were mesured during RAN tsk nd compred cross groups. Results: A stepwise pttern of RAN performnce ws oserved, with individuls with ASD demonstrting the slowest nming cross ll RAN conditions, controls demonstrting the fstest nming, nd silings demonstrting intermedite performnce. Individuls with ASD exhiited smller EVSs thn controls on ll RAN conditions, nd silings exhiited smller EVSs during numer nming (the most highly utomtized type of nming). EVSs were correlted with nming times in controls only, nd only in the more utomtized conditions. Conclusions: These results suggest tht reduced utomticity in the component processes of RAN my underpin differences in individuls with ASD nd their silings. These findings lso provide further support tht RAN ilities re impcted y genetic liility to ASD. This study hs importnt implictions for understnding the underlying skills contriuting to lnguge-relted deficits in ASD. Keywords: Autism spectrum disorder, Silings, Lnguge, Rpid utomtized nming, Eye trcking, Endophenotype Bckground Autism spectrum disorder (ASD) is chrcterized y socil-communictive impirments nd repetitive interests nd ehviors [1]. Lnguge impirments nd executive dysfunction hve lso een widely documented in individuls with ASD, nd milder differences hve een oserved in their first-degree reltives, suggesting tht these deficits my e ssocited with the genes tht * Correspondence: m-losh@northwestern.edu 1 Roxelyn nd Richrd Pepper Deprtment of Communiction Sciences nd Disorders, Northwestern University, Evnston, IL 60208, USA Full list of uthor informtion is ville t the end of the rticle cuse ASD [2-4]. Studying the underlying sources of such differences cn lend insight into the neurl nd genetic mechnisms of ASD. The present study mesured eye movements, s n index of utomticity, during rpid utomtized nming (RAN) [5-8] in individuls with ASD nd their silings. RAN involves nming colors, numers, digits, or ojects, repeted rndomly cross severl rows in visul rry, with fster nming indicting etter performnce. Previous studies hve shown tht RAN is impired in individuls with ASD nd their prents [9,10], though the sic processes tht contriute to these impirments remin uncler Hogn-Brown et l.; licensee BioMed Centrl Ltd. This is n Open Access rticle distriuted under the terms of the Cretive Commons Attriution License ( which permits unrestricted use, distriution, nd reproduction in ny medium, provided the originl work is properly credited. The Cretive Commons Pulic Domin Dediction wiver ( pplies to the dt mde ville in this rticle, unless otherwise stted.

2 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 Pge 2 of 11 The mnner in which eye movement is ffected in ASD hs ecome topic of intensive inquiry, with results generlly showing tht wheres reflexive eye movements pper unffected in ASD, significnt differences re oserved in eye movements relted to volitionl control of ttention, prticulrly when looking t scenes with socilly relevnt content [11]. In the present reserch, eye movements re used s mesure of how individuls smple informtion from the environment s they perform complex tsk tht requires sustined ttention. Thus, this study does not seek generl chrcteriztion of the nture of eye movements in ASD ut insted uses eye movements s source of moment-tomoment informtion out how individuls with ASD, silings of individuls with ASD, nd typiclly developing individuls perform in lnguge-sed tsk, moving eyond simple correltions of generl lnguge ility mesured seprtely to exmine within-tsk ssocitions etween eye movement nd lnguge processing. RAN is complex tsk, requiring confluence of severl coordinting processes, including executive functions (e.g., working memory, inhiitory control) nd linguistic processes (e.g., phonologicl retrievl, visul-verl connections). Becuse it tps rod rnge of neurocognitive functions, RAN hs een utilized to study the cognitive nd neuroiologicl mechnisms of severl disorders, including dyslexi, specific lnguge impirment, nd ttention deficit/hyperctivity disorder. In prticulr, eye trcking hs provided clues out the skill deficits underlying RAN difficulties [12-15]. For exmple, Pn nd collegues [15] investigted eye-voice spn (EVS), the numer of items hed the eyes re when trget item is nmed, in dyslexic nd norml reders. EVS is reflection of the extent to which utomticity in the processes underpinning RAN hs een chieved. In typiclly developing individuls, utomticity in reding-relted skills (such s RAN) is estlished through extensive prctice nd results in diminished need for ttentionl control, thus freeing up vrious ttentionl processes (e.g., working memory) [16]. During RAN, greter utomticity llows more informtion to e stored redily in phonologicl working memory, enling the eyes to move further hed to prepre upcoming responses nd resulting in fster nming. Pn nd collegues hypothesized tht reduced utomticity contriutes to the impirments oserved in dyslexi. They mesured EVS during numer nd dice RAN tsks. Becuse numer nming is highly utomtized in typicl reders, ut dice nming is not, lrger group differences were nticipted in the numer tsk. Groups differed on EVS for oth conditions, ut group differences in the numer RAN tsk were much lrger. Furthermore, EVS predicted overll nming speed only in the numer tsk nd only in controls. These results suggest tht disruption in the development of the utomticity of lnguge-relted mechnisms (e.g., phonologicl processing, visul-verl mpping) is one potentil cuse of oservle deficits in RAN performnce. The primry ojective of the present study ws to investigte lnguge-relted utomticity in ASD y exmining eye-voice reltionships during RAN. We hypothesized tht reduced utomticity of the processes underlying RAN leds to impirments in ASD. Thus, we predicted tht individuls with ASD, nd to lesser extent silings, would demonstrte smller EVSs thn controls nd tht these differences would e especilly pronounced in highly utomtized conditions (i.e., letter nd numer nming). We lso imed to chrcterize RAN ility in silings of individuls with ASD to determine the presence of differences similr to those found previously in prents of individuls with ASD [9,10]. We hypothesized tht RAN performnce is impcted negtively y genetic liility to ASD nd tht silings would therefore demonstrte similr (ut milder) impirments s individuls with ASD. Methods Prticipnts Prticipnts included 21 individuls with ASD, 23 silings of individuls with ASD, nd 24 control sujects, group-mtched on chronologicl ge. Prticipnts were selected from lrger fmily genetic study of ASD. Generl inclusion criteri included () minimum chronologicl ge of 15 yers, () minimum verl IQ of 80, (c) English s the primry lnguge spoken in the home, nd (d) no significnt visul impirment or color lindness. Control sujects were screened for fmily history of ASD or dyslexi. Individuls with ASD were included if they hd previous dignosis of ASD, confirmed y gold stndrd dignostic mesures. Silings were included if they hd t lest one siling with ASD, with dignosis confirmed through the lrger study. The Autism Dignostic Oservtion Schedule (ADOS; ADOS-2) [17,18] revised lgorithms nd comprison scores [18,19] were used to confirm ASD dignosis nd ssess ASD severity. Of the prticipnts with ASD, 14 met the cutoff for utism spectrum disorder. Seven of the prticipnts in the ASD group scored just elow the cutoff. Five of these prticipnts met dignostic threshold on the Autism Dignostic Interview-Revised (ADI-R) [20] nd hd prior clinicl dignosis, nd so were included in the study. The remining two individuls did not meet criteri on the ADI-R. However, oth prticipnts hd documented clinicl dignosis of ASD, nd clinicl judgment determined tht their current ehviors were consistent with ASD. IQ ws mesured y either the Wechsler Arevited Scle of Intelligence (WASI) [21] or the Wechsler Adult Intelligence Scle-

3 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 Pge 3 of 11 Third or Fourth Editions (WAIS-III; WAIS-IV) [22,23]. Prticipnt detils re included in the Tle 1. To exmine the reltionship etween utistic symptomtology nd RAN performnce, we ssessed ASD severity nd lnguge fetures conceptully relted to RAN performnce. ASD severity ws clculted from the ADOS using the Overll, Socil Affect, nd Repetitive nd Restricted Behviors comprison scores [18,19]. History of lnguge dely ws ssessed continuously y the Age of First Single Words nd Age of First Phrses items on the ADI-R (items 9 nd 10, respectively). The Prgmtic Rting Scle-School Age (PRS-SA, R Lnd, unpulished) ws used to ssess suprsegmentl speech chrcteristics during semi-nturlistic converstionl lnguge smple. The PRS-SA is 33-item mesure tht cptures prgmtic lnguge violtions such s filure to provide the ckground informtion necessry to understnd topic, intrusive interrupting, nd topic persevertion. The Suprsegmentl Speech Chrcteristics suscle ssesses rte of speech, intontion, volume, lnguge formultion difficulties, nd stuttering, with higher scores indicting more prgmtic impirment, nd ws used in correltions. Prticipnts were tested in lortory spce or in the prticipnts' homes. All procedures were pproved y the Institutionl Review Bords t Northwestern University nd the University of North Crolin t Chpel Hill. Design nd stimuli The RAN stimuli cme from the Comprehensive Test of Phonologicl Processing (CTOPP) [24] nd included two trils ech of colors, letters, numers, nd ojects. The color items were chnged from squres to circles, nd the colors were djusted to e more distinguishle on the computer screen. No chnges were mde to the other conditions. Ech tril contined four rows of nine items. Additionl file 1 depicts the tril A stimuli. A Toii T60 (60 Hz; Toii Technology AB, Dnderyd, Sweden) eye trcker, clirted using stndrd 5-point grid, ws used to mesure eye movements. According to the mnufcturer's specifictions, this device hs typicl ccurcy of 0.5 of visul ngle. Speech ws recorded using n externl USB microphone. Stimuli were presented on 17-in. TFT LCD monitor (1,280 1,024 resolution) with the prticipnt seted pproximtely in. wy. For ech condition, prticipnts first nmed prctice rry. Prticipnts were instructed to complete ech tril s quickly nd ccurtely s possile. Dt nlysis The re of interest (AOI) for ech item ws defined s region extending verticlly nd horizontlly from the center of ech item to the midpoint etween ech djcent item, with the horizontl size of n AOI eing pproximtely 3.9 of visul ngle given the monitor size nd the prticipnt's distnce to the monitor. The visul ngles of the items themselves were pproximtely 2.7 for ojects, 2.0 for colors, nd 1.4 for oth letters nd numers. Fixtions were ssigned to n AOI sed on their sptil coordintes. Consecutive fixtions within the sme AOI were pooled. Fixtions less thn 80 ms were excluded from nlyses, s these re typiclly ssocited with trcker error [25]. The Penn Phonetics L Forced Aligner [26], n utomtic phonetic lignment toolkit, ws used to locte the oundries of ech vocl response nd ssign lel sed on the form of the speech wve nd the expected response. Boundries nd response lels were then mnully edited to reflect the ctul response. Unexpected responses were mrked s errors (e.g., sustitutions, skips) or dysfluencies (e.g., stmmered responses, fillers). The onset nd offset of ech utternce ws synced to the eye movement dt sed on the zero point onset of ech tril. Tle 1 Prticipnt chrcteristics Chrcteristic ASD group Siling group Control group p vlue (n = 21) (n = 23) (n = 24) Mle, n (%) 15 (71.43) 8 (34.78) 10 (41.67).037 Age, men (SD), yers (3.69) (4.20) (3.37).607 Age, rnge Full scle IQ, men (SD) (14.85) (8.65) (9.80).001 c Full scle IQ, rnge Verl IQ, men (SD) (15.75) (10.94) (11.83).001 d Verl IQ, rnge Performnce IQ, men (SD) (16.59) (8.81) (10.12).049 e Performnce IQ, rnge χ 2 (2) = 6.60; ASD > siling (Bonferroni-djusted pirwise comprisons). F(2, 67) = c F(2, 67) = 8.67; ASD < siling, control (Bonferroni-djusted pirwise comprisons). d F(2, 67) = 7.97; ASD < siling, control (Bonferroni-djusted pirwise comprisons). e F(2, 67) = 3.17; no pirwise group differences.

4 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 Pge 4 of 11 Totl nming time ws clculted s the time etween the onset of the first item's lel nd offset of the lst item's lel. Totl nming times for trils A nd B of ech RAN condition were verged to produce one men nming time per condition. Similrly, frequency of errors nd EVSs were verged cross oth trils. EVS ws defined s the numer of items hed the eyes were when rticultion of trget item's nme egn. EVSs were omitted for errors or dysfluencies, s well s the two susequent responses, ecuse eye movement ptterns re often disrupted following errors s prticipnts regress nd correct themselves. Vocl responses nd corresponding EVSs were omitted for the first two columns nd lst column of ech tril ecuse of mistrgeting of the long sccdes ck to the eginning of row. Any EVS vlues less thn 1 nd greter thn 5 were omitted, s they re likely due to poor trcking. Following these criteri, EVSs were omitted for 12.02% of items for the ASD group, 6.68% of items for the siling group, nd 5.34% of items in the control group. Anlysis of vrince (ANOVA) indicted significnt group differences on the proportion of EVSs omitted (F(2, 65) = 5.32, p <.01), with Bonferroni-djusted pirwise comprisons reveling tht the ASD group hd significntly lrger percentge of EVSs omitted thn the control group (p <.05). Sttisticl nlysis Totl nming time, frequency of errors, nd EVS were exmined using mixed model repeted mesures nlysis of covrince (ANCOVA). Group ws entered s the etween-sujects fctor, nd full scle IQ (FSIQ) ws entered s covrite to ccount for group differences in IQ. To exmine performnce within sujects, we first nlyzed performnce cross more nd less utomtized conditions, y verging the Letter nd Numer conditions, nd Color nd Oject conditions together to form two domins (i.e., Letter/Numer, Color/Oject). We then repeted the model to nlyze ptterns of performnce in ll four individul conditions (i.e., Letter, Numer, Color, Oject). Becuse group differences cross different domins nd conditions were of primry interest in the study, Bonferroni-djusted pirwise comprisons for ech domin nd condition were exmined even if the domin/condition y group interction effect ws non-significnt. An lph criterion of.05 ws dopted for ll models, ut p vlues of <.10 re noted s mrginlly significnt. All pirwise comprisons were Bonferroni-djusted to ccount for multiple comprisons. Prtil correltions were used to exmine the reltionship etween EVS nd nming time for the Letter/ Numer nd Color/Oject domins, while controlling for full scle IQ. For these six correltions, the Bonferroni djustment ws used to lter the lph criterion to.008. In order to determine whether RAN performnce ws ssocited with ny mesures of ASD symptomtology, we investigted the correltion etween RAN vriles nd utistic symptomtology (e.g., ADOS comprison scores, lnguge/communiction ilities). Becuse of the explortory nture of these nlyses nd the numer of correltions exmined (n = 24), we djusted the lph criterion using the Bonferroni djustment, resulting in n lph criterion of.002. Results Nming time Preliminry ssumptions testing of the nming time dt identified one outlier. This prticipnt, from the ASD group, hd n verge RAN nming time tht fell more thn 3 SDs ove the men. This prticipnt's dt were omitted from ll nlyses involving nming time. Additionlly, one ASD prticipnt nd one control suject showed color nming errors suggestive of color lindness, so their dt were excluded from ll nlyses (i.e., nming time, error, nd EVS nlyses). First, we exmined nming time cross more nd less utomtized domins (i.e., y verging the Letter nd Numer conditions, nd Color nd Oject conditions together to form two domins) using mixed design repeted mesures ANCOVA. Tests of etween-sujects effects indicted min effect of group (F(2, 61) = 9.17, p <.001, prtil η 2 =.23), nd Bonferroni-djusted pirwise comprisons indicted tht the ASD group demonstrted slower nming times thn the control group (p <.001). The differences etween the silings nd the ASD nd control groups were mrginlly significnt t p =.07 nd p =.08, respectively. No min effect of IQ ws oserved (F(1, 61) = 1.40, p =.24, prtil η 2 =.02). There ws min effect of domin (F(1, 61) = 5.22, p <.001,prtil η 2 =.20) in tht Color/Oject nming time ws significntly slower thn Letter/Oject nming time (p <.001). No domin y group interction emerged (F(2, 61) = 2.62, p =.11, prtil η 2 =.06). However, plnned post-hoc comprisons indicted divergent group performnce cross domins. For Letter/Numer nming, the ASD nd siling groups oth demonstrted slower nming times thn the control group (ps <.05), while for Color/Oject nming, the siling group did not differ from the control group (p =.42), nd oth groups were significntly fster thn the ASD group (ps <.05). Figure 1 illustrtes this interction. Nming time ws then exmined for ech of the four different RAN conditions. To investigte specific ptterns cross conditions, mixed design repeted mesures ANCOVA ws utilized. In tests of etween-sujects effects, min effect of group emerged (F(2, 61) = 9.18, p <.001, prtil η 2 =.23). Bonferroni-djusted pirwise comprisons indicted tht the ASD group demonstrted slower nming thn the control group (p <.001), nd the

5 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 Pge 5 of 11 Nming Time (s) Letter/Numer Color/Oject Domin Figure 1 Line grph of domin y group interction for nming time. Groups with different superscripts differ t p <.05. ASD Siling Control differences etween the silings nd the ASD nd control groups were mrginlly significnt t p =.07 nd p =.08, respectively. No min effect of IQ ws oserved (F(1, 61) = 1.42, p =.24,prtilη 2 =.02). Within sujects, min effect of condition emerged (F(3, 183) = 8.94, p <.001, prtil η 2 =.21), nd ll Bonferroni-djusted pirwise comprisons etween conditions were significnt (ps <.01). The interction etween condition nd group ws mrginlly significnt (F(6, 183) = 1.94, p =.08,prtil η 2 =.06). Plnned Bonferroni-djusted pirwise comprisons showed tht on the Letter nd Numer conditions, the ASD nd siling groups demonstrted slower nming thn the control group (ps <.05). On the Color condition, the ASD group differed from control group (p <.001), nd the difference etween the ASD group nd siling group ws mrginlly significnt (p =.09). Finlly, on the Oject condition, the ASD group differed from oth silings nd controls (ps <.05). Figure 2 illustrtes this interction. The distriution of nming times for the individul RAN conditions is illustrted in Figure 3. Nming errors Becuse errors cn influence nming time, we investigted error frequency to determine whether group differences in error rtes contriuted to the oserved nming time differences. One prticipnt from the ASD group ws identified s n outlier in tht his error rte fell more thn 3 SDs ove the men. This ws different prticipnt from the outlier identified for nming time nlyses. This prticipnt's dt were excluded from ll error rte nlyses. As ws done with the nming time nlyses, error rtes were first exmined cross more nd less utomtized domins, using mixed design repeted mesures ANCOVA. Tests of etween-sujects effects reveled min effect of IQ (F(1, 61) = 8.25, p =.01, prtil η 2 =.12), ut no min effect of group (F(2, 61) = 2.38, p =.10,prtil η 2 =.07). Tests of within-sujects effects indicted min effect of domin (F(1, 61) = 5.27, p =.03, prtil η 2 =.08), though the pirwise comprisons were not significnt (p =.70). Additionlly, domin y IQ interction emerged (F(1, 61) = 5.10, p =.03, prtil η 2 =.08). No domin y group interction ws oserved (F(2, 61) = 0.71, p =.50, prtil η 2 =.02). A similr pttern ws oserved when mixed design repeted mesures ANCOVA ws employed to investigte error rtes cross the four individul RAN conditions. Tests of etween-sujects effects indicted significnt min effect of IQ (F(1, 61) = 8.25, p <.01, Nming Time (s) Letter Numer Color Oject Condition Figure 2 Line grph of condition y group interction for nming time. Groups with different superscripts differ t p <.05., ASD Siling Control

6 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 Pge 6 of 11 Figure 3 Box plot displying distriution of nming time (seconds) cross groups for the four RAN conditions. The interqurtile rnge (IQR), etween the 25th nd 75th percentile, is indicted y the lower nd upper oundries of ech ox, respectively. The horizontl line indictes the medin vlue. Outliers (vlues IQRs from the end of the ox) re denoted y circle. prtil η 2 =.12), ut no min effect of group (F(2, 61) = 2.38, p =.10, prtil η 2 =.07). Within sujects, min effect of condition (F(3, 183) = 3.18, p =.03, prtil η 2 =.05) ws reveled. The condition y IQ interction ws mrginlly significnt (F(3, 183) = 2.60, p =.05,prtil η 2 =.04). No condition y group interction ws oserved (F(6, 183) = 0.30, p =.94,prtilη 2 =.01). Eye-voice spn Due to poor eye trcking, dt for three individuls with ASD, one siling, nd one control suject were excluded from eye-voice spn (EVS) nlyses. EVSs were first exmined cross domins using mixed design repeted mesures ANCOVA. Between sujects, significnt min effect of group emerged (F(2, 57) = 9.27, p <.001, prtil η 2 =.25). Pirwise comprisons indicted tht the ASD group demonstrted significntly smller EVSs thn the siling nd control groups (ps <.01). The min effect of IQ ws mrginlly significnt (F(1, 57) = 2.87, p =.09, prtil η 2 =.05). Within sujects, no min effect of domin (F(1, 57) =.55, p =.46, prtil η 2 =.01) nd no interction etween domin nd IQ (F(1, 57) =.01, p =.94, prtil η 2 =.00) were oserved. A significnt interction etween domin nd group emerged (F(2, 57) = 6.43, p <.01, prtil η 2 =.18). Bonferroni-djusted pirwise comprisons indicted tht the ASD group demonstrted smller EVSs thn the siling nd control groups during Letter/Numer nming (ps <.05). The difference etween the siling nd control groups ws mrginlly significnt (p =.09). During Color/Oject nming, the ASD group demonstrted smller EVSs thn oth silings nd controls (ps <.01), nd the siling nd control groups did not differ (p = 1.00). Figure 4 illustrtes this interction. EVSs were then exmined for ech of the four RAN conditions, using mixed design repeted mesures ANCOVA. Between sujects, significnt min effect of group emerged (F(2, 57) = 9.27, p <.001, prtil η 2 =.25). Bonferroni-djusted pirwise comprisons indicted tht the ASD group demonstrted smller EVSs thn the siling nd control groups (ps <.01). The effect of IQ ws mrginlly significnt (F(1, 57) = 2.87, p =.09, prtil η 2 =.05). Tests of within-sujects effects indicted no min effect of condition (F(3, 171) =.31, p =.82, prtil η 2 =.01) nd no condition y IQ interction (F(3, 171) =.05, p =.99, prtil η 2 =.00). A significnt interction etween condition nd group did emerge (F(6, 171) = 4.35, p <.001, prtil η 2 =.13). Bonferroni-djusted pirwise comprisons reveled tht in the Letter condition, the ASD group demonstrted smller EVSs thn the control group (p <.01). The difference etween silings nd controls ws non-significnt (p =.63) though the differences etween silings nd the ASD group were mrginlly significnt (p =.08). In the Numer condition, oth the ASD nd siling groups hd significntly smller EVSs thn

7 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 Pge 7 of 11 Eye-Voice Spn (# of items) Letter/Numer Color/Oject Domin Figure 4 Line grph of domin y group interction for eye-voice spn (EVS). Groups with different suscripts differ t p <.05. ASD Siling Control controls (ps <.05), nd the difference etween the ASD nd siling groups ws mrginlly significnt (p =.08). In the Color nd Oject conditions, the ASD group hd smller EVSs thn oth silings nd controls (ps <.05). This interction is depicted in Figure 5. Figure 6 illustrtes the distriution of EVS cross the four conditions. Correltions etween EVS nd nming time Prtil correltions, controlling for FSIQ, were utilized to determine whether EVS ws relted to nming times in more nd less utomtized conditions. To ccount for the numer of tests eing run (n = 6), Bonferroni djustment ws implemented, resulting in n djusted lph criterion of.008. In the ASD group, EVSs were not correlted with nming time in Letter/Numer (r(13) =.35, p =.20) or Color/Oject domins (r(13) =.09, p =.75). In the siling group, EVSs were correlted with nming time in the Color/Oject domin (r(19) =.53, p =.01) though this correltion did not meet the djusted lph criterion of.008. EVSs nd nming time were not correlted for the Letter/Numer domin in silings (r(19) =.33, p =.14). In controls, EVS nd nming time were highly correlted in the Letter/Numer domin (r(20) =.66, p <.001), ut the correltion in the Color/Oject domin (r(19) =.55, p =.01) did not meet the djusted lph criterion. Correltions etween RAN vriles nd prticipnt chrcteristics In explortory nlyses, we investigted the reltionship etween utistic symptomtology, lnguge-relted mesures, nd RAN performnce in individuls with ASD. Specificlly, RAN nming time nd EVS were exmined in reltion to ADOS comprison scores, PRS-SA suprsegmentl score, Age of First Single Words, nd Age of First Phrses. Prtil correltions were used, controlling for FSIQ. Nming time in the more utomtized conditions (i.e., Letter/Numer) ws correlted with the ADOS overll comprison score (r(17) =.50, p =.03) nd socil ffect comprison scores (r(17) =.58, p <.01). However, neither of the correltions met the djusted lph criterion of.002. The other correltions etween EVS nd utistic symptomtology were not significnt. Tle 2 includes the rs nd degrees of freedom for ech correltion. Discussion This study imed to determine whether utomticity during RAN, s mesured y EVS, is disrupted in individuls Eye-Voice Spn (# of items) , Letter Numer Color Oject Condition ASD Siling Control Figure 5 Line grph of condition y group interction for eye-voice spn (EVS). Groups with different suscripts differ t p <.05.

8 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 Pge 8 of 11 Figure 6 Box plot displying distriution of eye-voice spn (# of items) cross groups for the four RAN conditions. The interqurtile rnge (IQR), etween the 25th nd 75th percentile, is indicted y the lower nd upper oundries of ech ox, respectively. The horizontl line indictes the medin vlue. Outliers (vlues IQRs from the end of the ox) re denoted y circle, nd extreme vlues (vlues >3 IQRs from the end of the ox) re mrked y n sterisk. with ASD nd their silings. We lso sought to clrify the impct of ASD-relted genetic liility on RAN ilities y compring RAN performnce nd EVS in individuls with ASD, silings of individuls with ASD, nd controls. Findings suggest tht oth individuls with ASD nd their silings exhiit RAN difficulties reltive to gemtched controls, even when IQ is controlled. A stepwise pttern of RAN performnce ws oserved, with individuls with ASD demonstrting the poorest performnce, controls demonstrting the est performnce, nd silings demonstrting intermedite performnce. Furthermore, letter nd numer nming ws prticulrly ffected in silings, who, long with individuls with ASD, exhiited slower nming thn controls. In other words, in conditions tht typiclly involve higher degree of utomticity, silings showed difficulties reltive to controls. Tle 2 Prtil correltions etween utistic symptomtology nd RAN performnce, controlling for full scle IQ Letter/Numer nming time Color/Oject nming time Letter/Numer EVS Color/Oject EVS ADOS overll severity score r.50* df ADOS SA comprison score r.58** df ADOS RRB comprison score r df Age of First Single Words r df Age of First Phrses r df PRS-SA suprsegmentl score r df *p <.05; **p <.01.

9 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 Pge 9 of 11 Similr findings were found in nlyses of EVS, which reflects the extent to which the processes underlying RAN hve ecome utomtized (i.e., re performed without conscious effort). Individuls with ASD demonstrted shorter EVSs thn controls cross ll conditions, ut silings exhiited shorter EVSs only in the numer condition, the most highly utomtized type of nming. These findings suggest tht in conditions in which nming processes re highly utomtized, individuls with ASD nd silings require more ttentionl resources thn controls to complete the tsk. However, in conditions tht re less utomtized, silings demonstrte ptterns similr to those of controls, nd individuls with ASD continue to demonstrte difficulties. These results support the hypothesis tht the development of utomticity in lnguge-relted skills my e disrupted in individuls with ASD nd, to lesser extent, their silings. This dissocition etween performnce in more nd less utomtized conditions in the ASD nd siling groups is interesting nd requires further investigtion. Severl studies hve suggested tht different cognitive processes likely contriute to letter/numer vs. color/oject nming. In prticulr, it ppers tht linguistic processes (e.g., phonologicl processing, visul-verl mppings) re more closely tied to letter nd numer nming, while executive function is highly ssocited with color nd oject nming. For exmple, it hs een shown tht children with AD/HD, who re chrcterized y deficits in executive function, differ from typiclly developing controls only on color nd oject nming [27]. Furthermore, seprte study of typiclly developing children found tht color nming is highly correlted with rod rnge of executive functions, including inhiitory control, working memory, nd set shifting ility [28]. Reltionships etween these executive functions nd letter nd numer nming were not oserved, suggesting tht executive function plys role primrily in conditions where utomticity in underlying lnguge processes hs not een estlished (i.e., in color/oject nming). The findings in the current study suggest tht individuls with ASD, ut not their silings, hve difficulty with color/oject nming reltive to controls. Thus, it is possile tht silings nd controls re le to recruit dequte executive functions to support less utomtized nd effortful nming (i.e., color/ oject nming), wheres individuls with ASD re not. It will e importnt for future studies to ddress this question. Some limittions should e considered. The reltively smll smple size nd nrrow rnge of chronologicl ge nd IQ of prticipnts my limit generliztion of results to roder popultion of individuls with ASD nd their fmilies. Additionlly, the low numer of siling pirs tht were included in this study prevented investigtion into the fmilility of RAN ilities. Losh nd collegues [10] reported fther-child correltions in nming time in smll numer of prent-child dyds, providing preliminry evidence tht RAN ilities re fmilil in ASD. Studies of lrger smples of prentchild dyds nd siling pirs re needed efore firm conclusions cn e drwn out the fmilility of RAN performnce. It is lso importnt to note tht while the findings of RAN differences in silings suggests tht genetic risk to ASD my impct the processes underpinning RAN performnce, environmentl influences my lso contriute in some wy to RAN ilities. However, prior reserch on individuls with dyslexi nd their fmilies, s well s typiclly developing popultions, suggests tht genetic influences ply significnt role in RAN ilities. For exmple, twin studies hve demonstrted the heritility of RAN performnce [29-31], nd RAN ility lso ppers to e impired in silings of children with dyslexi, even those who do not develop reding disility lter in life [32]. Furthermore, RAN performnce hs een included in genetic studies of dyslexi, resulting in the identifiction of severl ssocited genomic regions [33,34]. Thus, while the present study cnnot definitively conclude tht similrities etween individuls with ASD nd their silings derive from genetic influence, when tken together with prior reserch, the present findings offer preliminry evidence tht RAN my e good cndidte for further investigtions of mrkers of genetic liility to ASD. Interestingly, the results of this study re similr to Pn nd collegues' recent findings of shorter EVS nd slower nming time in highly utomtized RAN tsk in children with dyslexi [15]. The possiility tht RAN impirments in ASD nd dyslexi stem from similr underlying deficits is potentilly importnt in tht some neuroiologicl mechnisms of dyslexi could e implicted in ASD s well. For exmple, RAN performnce hs een linked to structurl differences in the cereellum in children with dyslexi [35,36], nd impired RAN performnce hs een reported in cses of cereellr degenertion [37]. Furthermore, fmri studies hve demonstrted tht the RAN tsk engges the regions of the rin involved in reding nd eye movement plnning [38], nd decresed functionl connectivity etween criticl rin res hs lso een ssocited with RAN deficits [39]. The identifiction of the neurologicl functions ssocited with RAN suggests tht RAN my e useful focus of future neuroimging studies of ASD. For exmple, inclusion of covert RAN tsks in neuroimging studies of individuls with ASD nd their firstdegree reltives my provide informtion out the potentil connection etween neurologicl differences nd the roder lnguge-relted difficulties oserved in ASD.

10 Hogn-Brown et l. Journl of Neurodevelopmentl Disorders 2014, 6:33 Pge 10 of 11 Conclusions This is the first study to utilize eye trcking technology to investigte the processes underpinning RAN performnce in individuls with ASD nd their first-degree reltives. Our findings suggest tht disruption in the utomticity of RAN-relted mechnisms, s evidenced y shorter eye-voice spns (EVSs), is present in oth individuls with ASD nd their silings. This study hs importnt implictions for understnding lnguge-relted deficits in ASD. In prticulr, our findings re similr to those of recent study documenting reduced utomticity of RAN processes in children with dyslexi [15]. Given wht is currently understood out the neuroiologicl mechnisms of dyslexi, future studies should consider utilizing RAN tsks to investigte potentilly overlpping mechnisms (e.g., cereellr dysfunction) in ASD. This study is lso the first to estlish tht RAN ilities re impcted in otherwise unffected silings of individuls with ASD, providing further support of the hypothesis tht RAN ilities re impcted y genetic liility to ASD [9,10]. Additionl file Additionl file 1: Tril A stimuli. A file showing tril A stimuli for Color, Letter, Numer, nd Oject conditions of the RAN tsk (dpted from CTOPP [24]). Arevitions ADOS: Autism Dignostic Oservtion Schedule; ASD: Autism spectrum disorder; EVS: Eye-voice spn; RAN: Rpid utomtized nming. Competing interests The uthors declre tht they hve no competing interests. Authors contriutions All uthors were involved in the conceptul design of the study, nlysis nd interprettion of dt, nd criticl revision of the mnuscript for importnt intellectul content. AHB ssisted with dt collection, conducted the sttisticl nlyses, nd drfted the mnuscript. ML nd PCG otined funding, supervised the study, nd provided dministrtive, technicl, nd mteril support. All uthors red nd pproved the finl mnuscript. Acknowledgements This study ws supported y grnts R01DC nd T32DC from the Ntionl Institute of Defness nd Other Communiction Disorders. The study sponsors hd no role in the design nd conduct of the study; collection, mngement, nlysis, nd interprettion of the dt; preprtion, review, or pprovl of the mnuscript; nd decision to sumit the mnuscript for puliction. We lso cknowledge the support of the Reserch Prticipnt Registry Core of the Crolin Institute for Developmentl Disilities (P30HD03110) for their role in prticipnt recruitment. The uthors would like to thnk Sejl Shh nd Bret Krvis for their ssistnce with dt processing. The uthors re lso grteful to the individuls nd fmilies who prticipted in this study. Author detils 1 Roxelyn nd Richrd Pepper Deprtment of Communiction Sciences nd Disorders, Northwestern University, Evnston, IL 60208, USA. 2 Deprtment of Psychology, University of North Crolin t Chpel Hill, Chpel Hill, NC 27599, USA. 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