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Journal of Autism and Developmental Disorders, Vol. 33, No. 5, October 2003 ( 2003)

Abnormal Brain Lateralization in High-Functioning Autism

Paul R. Escalante-Mead,1 Nancy J. Minshew,2 and John A. Sweeney1,3

Disturbances in lateral preference in autism are of interest because of their potential to shed lighton brain maturational processes in this disorder. Forty-seven autistic individuals with a historyof disordered early language development and 22 autistic individuals with normal early languageacquisition were matched with 112 healthy individuals and compared on a standardized mea-sure of lateral preference, the Edinburgh Handedness Inventory. Autistic individuals with a his-tory of early language disturbance showed more atypical cerebral dominance than both healthyparticipants and autistic individuals with normal early language skills. The data indicated mat-urational disturbances in establishing lateral preference rather than increased rates of left hand-edness. Atypical establishment of cerebral dominance may be one cause of disordered languagedevelopment in autism.

KEY WORDS: Autism; Aspergers disorder; pervasive developmental disorders; brain lateralization;handedness; neuropsychology.

Disturbance in the development of brain lateral-ization in autism is important for its potential to illu-minate the timing and nature of developmentaldisturbances in cerebral organization. Both genetic andenvironmental factors initiate lateralization in the fetalbrain as early as 12 weeks into gestation (McCartney& Hopper, 1999). Normal lateralization typically in-volves a relative left-hemisphere dominance for lan-guage and motor skills and relative right-hemispheredominance for spatial processing (Annett, 1999). Someinvestigations using standardized lateralization instru-ments have reported increased rates of left handednessin autism; however, more studies have reported in-creased rates of inconsistent lateral preference in com-parison with other developmentally handicappedpopulations (Bryson, 1990; Cornish & McManus, 1996;Fein, Humes, Kaplan, Lucci, & Waterhouse, 1984;Soper et al., 1986).

On dichotic listening tasks, disturbances in hemi-spheric specialization in autism are exemplified by areduced right-ear advantage for speech processing(Prior & Bradshaw, 1979). Autistic children show left-ear preference for both musical and verbal stimuli,whereas healthy children typically prefer to use theirleft ear for music and their right ear for verbal stimuli(Blackstock, 1978). Brain imaging studies of autismhave demonstrated reversed cortical asymmetries inanatomy and reversed patterns of regional cerebralblood flow that are consistent with a generalized dis-turbance in the establishment of a normal pattern ofcerebral dominance (Hier, LeMay, & Rosenberger,1979; Hashimoto et al., 2000; McAlonan et al., 2002).

Twin and family studies provide evidence thatautism is strongly genetically influenced (Folstein &Santangelo, 1999). Recent evidence attests that link-age signals obtained on chromosome 7q and at leastone signal on 13q can be attributed to the subgroupof families in which both autistic probands and theirparents had language delay (Bradford et al., 2001).This finding raises the question of whether earlydevelopmental language disturbances may be relatedto more general problems in brain organization in

1 University of Illinois at Chicago, Chicago, IL.2 University of Pittsburgh, Pittsburgh, PA.3 Correspondence should be addressed to John A. Sweeney, Center

for Cognitive Medicine, University of Illinois at Chicago, Chicago,IL 60612; e-mail: jsweeney@psych.uic.edu.

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Wechsler IQ scales (WISC-III or WAIS-R) to assessFull Scale, Verbal, and Performance IQ. Groups werematched on age, race, gender, and Full, and Verbal IQ(see Table I). All individuals were high functioning,with Full Scale and Verbal IQ scores of at least 75. Allautistic participants, regardless of their history of lan-guage development, met diagnostic criteria for autisticdisorder on both the Autism Diagnostic Interview-Revised (Lord, Rutter, & Couteur, 1994) and theAutism Diagnostic Observation Schedule or AutismDiagnostic Observation Schedule-G (Lord et al., 2000).The diagnosis of autism on these instruments was con-firmed by expert clinical opinion. All participants metcriteria for autism, but only a subset had a history onthe Autism Diagnostic Interview-Revised of delayed ordisordered early language development. Despite thisdifference in developmental history, at the time ofassessment, subjects in both groups presented with theimpairment in language comprehension typically asso-ciated with autism, but this was not severe enough tointerfere with subjects ability to comprehend the sim-ple phrases on our handedness inventory. No subjecthad a history of a medical disorder known to causeautistic features such as tuberous sclerosis or fragile-Xsyndrome. Healthy individuals had no current or pasthistory of a psychiatric or neurological disorder. Allparticipants provided informed consent before partici-pating in the study.

Laterality Assessment

Lateral dominance was ascertained using amodified version of the Edinburgh Handedness

autistic individuals with and without disordered lan-guage development.

The evaluation of hand preference during perfor-mance of various daily activities is a standard clinicalapproach for assessing cerebral dominance (Bryson,1990; Fein et al., 1984). In this study, we used theEdinburgh Handedness Inventory, which has not beencommonly used in previous studies of autism but is awidely accepted clinical instrument for the measurementof lateral preference (Raczkowski & Kalat, 1974). Wecontrasted lateral preference in autistic individuals witha history of early language disturbance with preferencein those whose early language abilities were not signif-icantly impaired. Prior studies of lateralization in autismhave not considered these subgroups separately, and theytypically used smaller samples and lower-functioningpatients than were employed in this study (Bryson, 1990;Fein et al., 1984; McManus, Murray, Doyle, & Baron-Cohen, 1992). Our prediction was that those with earlylanguage impairment would show greater evidence ofdisruption in hemispheric specialization that would bereflected in reduced right-hand dominance.

METHOD

Participants

Participants included 47 autistic individuals withdisordered early language development, 22 autisticindividuals with a history of normal early languageacquisition, and 112 healthy subjects. Participantswere administered the age-appropriate version of the

540 Escalante-Mead, Minshew, and Sweeney

Table I. Intelligence, Age, and Handedness Data from Healthy Individuals and Autistic Individuals with and without Early Language Delay (Standard Deviations in Parentheses)

Autism without Autism withHealthy disordered early disordered early

individuals language development language development(n = 112) (n = 22) (n = 47) Statistics

Age 18.82 18.42 16.85 F < 1(10.17) (13.83) (9.83)

Verbal 108.16 113.20 106.70 F(2,165) = 1.45IQ (12.37) (15.16) (17.71) n.s.Performance 106.20 108.10 101.64 F(2,165) = 2.02IQ (12.32) (15.98) (16.05) n.s.Full Scale 107.79 111.85 104.77 F(2,164) = 1.63IQ (12.94) (12.27) (17.15) n.s.Edinburgh Handedness 17.29 13.31 10.45 2(2) = 28.08Inventory (8.02) (12.80) (11.45) p < .01

(median: 19.00) (median: 19.00) (median: 15.00)

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[2(2) = 24.34, p < .01] (see Figure 1). The autisticindividuals with early language impairment had lowerrates of established lateral preference than the healthygroup [2(1) = 27.40, p < .01], as did autistic indi-viduals with normal early language acquisition[2(1) = 6.01, p < .05]. Autistic individuals with dis-ordered language development were not significantlydifferent from autistic individuals with normal earlylanguage acquisition. There were no group differencesin rates of left handedness [2(2) = 1.10, ns].

DISCUSSION

High-functioning autistic individuals with disor-dered early language development had significantly re-duced rates of established left or right lateral handpreference. Autistic individuals with normal early lan-guage acquisition had less pronounced but still signif-icantly reduced rates of established lateral preference,intermediate between the autistic individuals with dis-ordered language development and healthy individuals.This sample of high-functioning autistic individuals didnot demonstrate a pattern of increased rates of lefthandedness as observed in some prior studies (Cornishet al., 1996; Soper et al., 1986).

Inventory (Raczkowski & Kalat, 1974). The EdinburghHandedness Inventory is a self-report measure askingparticipants to state which hand or foot (right, left, orboth) would be used to perform a series of 23 tasksunder normal everyday conditions.

RESULTS

The assessment of lateral preference has bothquantitative (degree of lateral preference) and qualita-tive (left or right handed) dimensions. Therefore, weanalyzed data from this study in two ways. First, wecontrasted the three subject groups with raw scoresfrom the Edinburgh Handedness Inventory to assessdegree of lateralization, using a nonparametric testbecause the distributions were non-normal. Second,we contrasted the groups in rates of right-hand domi-nance and rates at which subjects established domi-nance of either hand based on scores from theEdinburgh scale.

A significant overall group difference on theraw scores of the Edinburgh Handedness Inventorywere ascertained using the Kruskal Wallis test[2(2) = 27.81, p < .01]. Follow-up tests with theMann-Whitney procedure revealed a less robustestablishment of right-hand preference in autistic par-ticipants with disordered language development ascompared with both healthy participants (z = 5.27,p < .01) and autistic individuals with normal earlylanguage acquisition (z = 2.63, p < .01) . There wasno significant difference between autistic individualswith normal early language acquisition and healthyparticipants.

To compare the prevalence of established hand-edness across groups, we applied a criterion of 17 ofthe 23 items from the Edinburgh scale scored withthe same lateral preference to identify those withreasonably well established lateral dominance. An over-all group comparison using a 2 analysis revealed a sig-nificant group difference in rates of established rightlateral dominance [2(2) = 28.5, p < .01]. Autisticindividuals with a history of disordered languagedevelopment had lower rates of right handedness thanhealthy individuals [2(2) = 25.21, p < .01], as didautistic individuals with normal early language acqui-sition [2(2) = 11.04, p < .01]. The two autism groupsdid not significantly differ in this regard.

A subsequent assessment of the presence or ab-sence of established lateral preference for either handrevealed a significant overall group difference forrates of failed establishment of lateral preference

Abnormal Brain Lateralization in High-Functioning Autism 541

Fig. 1. Percentages of left, right, and mixed lateral dominance inhealthy individuals and autistic individuals with and without earlylanguage delay, based on the Edinburgh Handedness Inventoryscores. L = left handed, R = right handed, M = mixed dominance.

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The results of this study confirm previous reportsdocumenting inconsistent cerebral dominance inautism (Bryson, 1990; Hauck & Dewey, 2001). Pre-vious studies have not compared lateral dominance ofsubgroups within the autism spectrum as defined bytheir early language abilities, nor have they typicallyfocused on a high-functioning population as in thisstudy. Our demonstration of an association betweenlateralization deficits in the motor domain and dis-turbances in early language acquisition represents anew observation, and a logical one given the well-established left-hemispheric specialization for lan-guage abilities.

Our observation of reduced cerebral dominance isconsistent with other findings indicating atypical re-gional specialization of brain function in autism.Studies of face recognition have suggested matura-tional disturbances in the specialization of localizedcircuitry for face recognition (Carver & Dawson,2002). Other studies have provided evidence of matu-rational disturbances of the interregional (Boddaert &Zilbovicius, 2002) and interhemispheric circuitry(Egaas, Courchesne, & Saitoh, 1995; Hardan,Minshew, & Keshavan, 2000; Keshavan et al., 2002)that underlie specialization and integration of regionalbrain function.

The association of dysmaturation in hemisphericspecialization with deficits in the early development oflanguage skills indicates that language disturbances inautism may be related to an atypical development ofleft-hemispheric specialization for language skills.Because language delay has been related to specificgenetic disturbances in autism (Bradford et al., 2001),it is possible that this linkage may result from a moregeneralized genetically mediated disturbance in thecerebral organizational events that give rise to special-ization in hemispheric function. In this context, thedegree of establishment of differentiated cerebrallateralization may complement linguistic endopheno-typic markers to enhance identification of neurobiolog-ically and genetically distinct subgroups of individualswith autism (Rinehart, Bradshaw, Brereton, & Tonge,2002).

ACKNOWLEDGMENTS

Funded by grants MH01433 and NS33355from the National Institute of Health and by an NICHDCollaborative Program of Excellence in Autism(HD35469).

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Raczkowski, D., & Kalat, J. W. (1974). Reliability and validity ofsome handedness questionnaire items. Neuropsychologia, 12,4347.

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