Journal of Autism and Developmental Disorders, Vol. 32, No.

4, August 2002 ( 2002)

Lateralization in Individuals with High-Functioning Autism and Aspergers Disorder: A Frontostriatal Model
Nicole J. Rinehart,1,3 John L. Bradshaw,2 Avril V. Brereton,1 and Bruce J. Tonge1

Neurobiological and behavioural studies of possible left hemisphere dysfunction in autism have generated conflicting results. Left hemisphere dysfunction may manifest in autism only in tasks that invoke executive functions. Moreover, left hemisphere dysfunction may underpin autism but not Aspergers disorder. We thus aimed to systematically investigate reports of anomalous lateralization in individuals with high-functioning autism and Aspergers disorder. Two of the tasks were sensitive to executive dysfunction: a serial choice reaction-time task and a Posner-type paradigm; the remaining tasks instead investigated aspects of perceptual lateralisation. Compared with age- and IQ-matched controls, the autism group displayed deficiencies in right hemispace (and by implication, left hemisphere) performance on both executive function tasks; however, this group demonstrated normal lateralization effects on the nonexecutive, visual-perceptual tasks. In contrast, the Aspergers disorder group showed similar laterality effects to their age- and IQ-matched controls on both executive and nonexecutive function tasks. The etiological relevance of this neurobehavioral dissociation between high-functioning autism and Aspergers disorder was discussed; in particular, it was suggested that the period where dominance shifts from right to left hemisphere is important in whatever process might dictate the emergence of either autism or Aspergers disorder.
KEY WORDS: High-functioning autism; Aspergers disorder; executive function; laterality; frontostriatal.

INTRODUCTION Autism is a neurodevelopmental disorder characterized by verbal and nonverbal deficiencies, poor social skills, and repetitive, restrictive, and stereotyped modes of behavioral response (American Psychiatric Association, 1994). Marked language delays and poor nonverbal communication constitute the earliest, and often the most tangible, features of autism. Indeed, early
1

Monash University Centre for Developmental Psychiatry, Monash Medical Centre, Clayton, Victoria, Australia, 3168. 2 Neuropsychology Research Unit, Monash University, Clayton, Victoria, Australia, 3800. 3 Correspondence should be addressed to Nicole J. Rinehart, Monash University Centre for Developmental Psychiatry, Monash Medical Centre, 246 Clayton Rd, Clayton, Victoria, Australia, 3168; e-mail: Nicole.Rinehart@med.monash.edu.au

neuropsychological research focused on the left hemisphere as a primary site of neurobiological disruption in autism. The left hemisphere dysfunction (LHD) theory is based on clinical and experimental observations that individuals with autism exhibit deficits in functions ascribed to the left hemisphere, such as language, sequential processing, and symbol use, together with preserved right hemisphere functions, such as drawing, music, and visual-spatial abilities (Blackstock, 1978; Dawson, 1983; Fein, Humes, Kaplan, Lucci, & Waterhouse, 1984; Jolliffe & Baron-Cohen, 1997; Prior & Bradshaw, 1979; Tanguay, 1976). Nonetheless, the generality of this LHD has been challenged. Using a neuropsychological test battery, Sussman and Lewandowski (1990) found that only sensorimotor scales uncovered LHD in a group of individuals with autism. Rumsey and Hamburger (1988) also failed to support the LHD 321
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322 theory. Their group of individuals with autism exhibited normal lateralization on tests of motor and sensoriperceptual functioning. In addition, basic language faculties, known to be mediated by the left hemisphere, were intact (e.g., syntax, semantic, phonology). These authors suggested that autistic deficiencies in language pertain more to pragmatics and dysprosodies of speech, characteristics of right hemisphere impairment. Consistent with this claim, Ozonoff and Miller (1996) demonstrated that the pragmatic deficits of individuals with autism correspond to the shortfalls observed in right hemisphere stroke patients. Sabbagh (1999) has also noted a number of extra-linguistic (p. 29) similarities between infants and children with right hemispheric deficiencies and those with autism. From a review of the neurobiological literature, Muller et al. (1999) concluded that unilateral left hemispheric impairment, if present, is probably subtle and in the context of generally normal functional asymmetry. Using single-photon emission computed tomographic imaging, Chiron et al. (1995) found hypofunction of the left hemisphere. Using a functional mapping paradigm, Muller et al. (1999) also reported reversed hemispheric dominance for specific language functions. Early imaging and scanning techniques, however, provided equivocal evidence for a left hemisphere deficit in autism. For example, although early computerized brain tomography revealed left hemispheric anomalies in the medial temporal lobe (Hauser, DeLong, & Rosman, 1975) and morphological anomalies near the left posterior language region (Hier, LeMay, & Rosenberger, 1979), these findings were not replicated by Damasio, Maurer, Damasio, and Chuis (1980) computed tomography study of 17 individuals with autism who tended to show bilateral dysfunction. More recent, positron emission tomography technology has also uncovered bilateral brain dysfunction (specifically, hypoperfusion in the temporal lobes) with no specific left hemisphere anomalies in children with autism (Zilbovicius et al., 2000). Controversial imaging and neuropsychological findings, together with the emergent notion that social rather than language dysfunction is primary to autism (Rutter & Bailey, 1993), moved the focus away from the LHD framework to neurobiologic circuitry models of autism (Minshew, Sweeney, & Bauman, 1997), such as the frontostriatal model of autism proposed by Bradshaw (2001). Indeed, it may be more profitable to examine LHD in the context of frontostriatal/executive dysfunction, rather than as a global phenomenon affecting all aspects of brain function mediated by the left hemisphere. The term executive functioning reflects

Rinehart, Bradshaw, Brereton, and Tonge the role of the frontostriatal region in coordinating cognitive-motor output so that behavior is well timed, planned, adaptable, appropriate, and relevant (Frith & Dolan, 1997; Miyake, Friedman, Emerson, Witzki, & Howerter, 2000; Stuss & Alexander, 2000). In support of a lateralized dysfunction of the frontostriatal circuitry, there is some neurobiological evidence to suggest that autism may be associated with functional anomalies in the left frontostriatal system; for example, Siegel et al. (1992) found that glucose metabolism was reduced in the left posterior putamen in a group of individuals with autism. In summary, the LHD theory in autism has often been disputed. The conflict may have arisen from the piecemeal approach of many investigations in this domain. Specifically, researchers have often disregarded the possibility that deficits may be related to the frontostriatal circuitry, rather than uniformly distributed across the hemispheres. The specific relationship between anomalous lateralization and frontostriatal deficiencies in autism may be demonstrated by showing normal lateralization on tasks that are not mediated by the frontostriatal circuitry and, at the same time, demonstrating hemispheric effects on executive function tasks that are sensitive to frontostriatal deficiencies. Fein, Humes, Kaplan, Lucci, and Waterhouse (1984) suggested that subtypes of autism may display characteristic modes of left hemisphere impairment. Unlike autism, Aspergers disorder is not associated with early language delays and has often been imputed to right, rather than left, hemisphere dysfunction. Although there is neurobehavioral evidence to support a right hemisphere deficit in Aspergers disorder (Ellis, Ellis, Fraser, & Deb, 1994), neuroimaging has uncovered evidence to support both left and right hemisphere abnormalities (Happ et al., 1996a; McKelvey, Lambert, Mottron, & Shevell, 1995). Dissociations in hemispheric functioning in autism and Aspergers disorder may point to neurobiological differences between these closely related disorders. This series of experiments assesses whether or not left hemisphere deficiencies are contingent on the extent to which a particular activity invokes executive functions and attention in autism and Aspergers disorder (AD). An anomaly of lateralization in the tasks sensitive to executive dysfunction, but not in the nonexecutive functional domain, would be consistent with Muller et al.s (1999) suggestion that anomalies of lateralization in autism are subtle and not continuously distributed across brain regions. Three unique experimental paradigms were used to assess laterality. A serial choice response-time par-

Lateralization in Autism and Aspergers Disorder adigm was used for the first laterality study. In this experiment, participants were required to press buttons along an illuminated light path; this action relies on cognitive-motor planning and shifting cognitive set in response to an unpredictable set of cues. The LHD theory would predict that the autism group would be slower at moving rightward and would also commit more rightward errors than the control group on this executive function task. A Posner-type task (Posner et al., 1988) was used to examine whether individuals with autism and AD tended to neglect visual stimuli (i.e., cues) presented in the right hemispace. This was measured by examining the number of times participants responded to cues before targets appeared in each hemispace. It was predicted that individuals with autism would neglect cues presented in right hemispace and thus would be less likely to execute an anticipation response on this side. An examination of anticipation responses, as opposed to actual target responses, provides a covert measure of the allocation of attention to left and right spatial locations, because it demonstrates when participants fail to use laterally presented advance information rather than their ability to merely respond to overtly presented targets. Indeed, normal lateralization effects in autism have been reported in Posner-type paradigms when only the overt target response is considered (Wainwright & Bryson, 1996). Two visual-perceptual tasks (gray scales, chimeric faces) that do not appear to be sensitive to functions subserved by the frontostriatal circuitry (see Nicholls, Bradshaw, & Mattingley, 2001) were used to examine

323 whether individuals with autism exhibit anomalous lateralization in nonexecutive function tasks. Both of these visual-perceptual tasks have been shown in stroke studies to be sensitive to unilateral impairment (Mattingley, Bradshaw, Bradshaw, & Nettleton, 1994a; Mattingley, Bradshaw, Nettleton, & Bradshaw, 1994b). It was predicted that neither the autism nor the AD group would show anomalous lateralization on these latter, nonexecutive tasks. METHODS Participants A group of children diagnosed with high-functioning autism (HFA), a group diagnosed with AD, and control groups matched according to age, sex, handedness, and full-scale IQ were recruited for each laterality experiment. The three groups of children with HFA and three groups of children with AD are described in Tables 1 to 3 (note that some children participated in more than one experiment). Only right-handed children were included in this study. One-way analyses of variance (ANOVA) confirmed no significant age difference between the HFA and control groups or the AD and control groups for each of the three experiments [Experiment 1: HFA, 9.1 years, controls, 9.2 years, F(1, 22) 0.002, p .97; AD, 12.8 years, controls 11.6 years, F(1, 22) 0.55, p .47. Experiment 2: HFA, 10.7 years, controls, 10.7 years, F(1, 20) 0.00, p .99; AD, 14.1 years, controls, 13.5 years, F(1, 16) 0.11, p .75. Experiment 3: HFA, 9.0 years, controls, 9.5

Table I. Experiment 1: High-Functioning Autism (HFA) and Aspergers Disorder (AD) Participants: Sex, Age, and Full-Scale IQ range (FIQ) FIQ range (IQ midpoint) AV LAV LAV AV AV AV LAV LAV AV AV LAV AV (99.5) (84.5) (84.5) (99.5) (99.5) (99.5) (84.5) (84.5) (99.5) (99.5) (84.5) (99.5) 93.3 7.7 AD participant 1 2 3 4 5 6 7 8 9 10 FIQ range (IQ midpoint) LAV SUP AV SUP HAV LAV BORD AV VSUP BORD (84.5) (124.5) (99.5) (124.5) (114.5) (84.5) (74.5) (99.5) (134.5) (74.5)

HFA participant 1 2 3 4 5 6 7 8 9 10 11 12 M SD

Sex M M M F M M M M M M M M

Age (years) 6.9 10.3 9.1 5.8 8.5 5.5 7.3 15.2 15.2 7.9 9.6 6.9 9.1 3.3

Sex M M M M M M M F M M

Age (years) 15.7 6.3 10.3 9.3 19 9.2 16.4 14.6 12.9 14.1

12.8 3.9

101.5 22.9

BORD, borderline; LAV, low average; AV, average; HAV, high average; SUP, superior; VSUP, very superior.

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Rinehart, Bradshaw, Brereton, and Tonge

Table II. Experiment 2: High-Functioning autism (HFA) and Aspergers Disorder (AD) Participants: Sex, Age, and Full-Scale IQ (FIQ) FIQ range (IQ midpoint) AV LAV LAV AV AV AV LAV LAV BORD AV LAV (99.5) (84.5) (84.5) (99.5) (99.5) (99.5) (84.5) (84.5) (74.5) (99.5) (84.5) 90.4 9.2 AD participant 1 2 3 4 5 6 7 8 9 FIQ range (IQ midpoint) SUP AV SUP HAV LAV BORD VSUP BORD LAV (124.5) (99.5) (124.5) (114.5) (84.5) (74.5) (134.5) (74.5) (84.5)

HFA participant 1 2 3 4 5 6 7 8 9 10 11 M SD

Sex M M M F M M M M M M M

Age (years) 8.7 12.1 11.7 7.5 10.7 7.1 8.4 16.0 16.1 11.3 8.3 10.7 3.2

Sex M M M M M M M M M

Age (years) 8.1 11.8 10.8 20.5 10.7 17.9 14.3 16.4 16.5

14.1 4.04

101.7 23.3

BORD, borderline; LAV, low average; AV, average; HAV, high average; SUP, superior; VSUP, very superior.

years, F(1, 22) 0.15, p .70; AD, 11.7 years, controls 10.6 years, F(1, 22) 0.36, p .55] (see Tables 1 to 3 for participant details). These participants were recruited in a similar way to that reported by Rinehart, Bradshaw, Moss, Brereton, and Tonge (2000). The participants with HFA fulfilled DSM-IV (American Psychiatric Association, 1994) criteria for autistic disorder. Likewise, the participants in the AD group satisfied DSM-IV (American Psychiatric Association, 1994) criteria for AD. Four experienced clinicians were involved in the diagnosis. Diagnostic information was gathered using the revised Autism Diagnostic Interview (Lord, Rutter, & Le Cou-

teur, 1994), structured parent interview, direct child observations, and information from other sources such as teachers and therapists. Participants were included only if their performance and verbal IQ exceeded 70. In addition, participants were excluded if they had previously experienced the following conditions: comorbid medical (e.g., tuberous sclerosis), hearing or visual, neurological (e.g., epilepsy), psychiatric (e.g., Tourettes, attention deficit hyperactivity disorder), or genetic disorders (e.g., fragile X disorder), other than the primary diagnosis of HFA or AD. The cognitive functioning of the HFA and AD group was established from previous cognitive assess-

Table III. Experiment 3: High-funtioning autism (HFA) and Aspergers Disorder (AD) Participants: Sex, Age, and Full-Scale IQ Range (FIQ) FIQ range (IQ midpoint) AV LAV LAV AV AV AV LAV LAV AV AV LAV AV (99.5) (84.5) (84.5) (99.5) (99.5) (99.5) (84.5) (84.5) (99.5) (99.5) (84.5) (99.5) 93.3 7.7 AD participant 1 2 3 4 5 6 7 8 9 10 11 12 FIQ range (IQ midpoint) LAV AV SUP AV SUP HAV LAV BORD AV VSUP LAV BORD (84.5) (99.5) (124.5) (99.5) (124.5) (114.5) (84.5) (74.5) (99.5) (134.5) (84.5) (74.5) 99.9 20.5

HFA participant 1 2 3 4 5 6 7 8 9 10 11 12 M SD

Sex M M M F M M M M M M M M

Age (years) 6.9 10.3 9.1 5.8 8.5 5.5 7.3 15.2 15.3 7.9 9.6 6.9 9.0 3.2

Sex M F M M M M M M F M F M

Age (years) 15.7 7 6.3 10.3 9.3 19 9.2 16.4 14.6 12.9 5.8 14.1 11.7 4.3

BORD, borderline; LAV, low average; AV, average; HAV, high average; SUP, superior; VSUP, very superior.

Lateralization in Autism and Aspergers Disorder ment undertaken at the time of diagnosis. If 3 or more years had lapsed since diagnosis, the cognitive function of participants was reassessed using an age-appropriate Wechsler intelligence test. It was only possible to report IQ range because some of the participating assessment services do not provide specific IQ scores. For the purposes of statistical comparison, the midpoint of each IQ range was utilised; for example, a full-scale IQ in the average range (90 to 109) was recorded as 99.5. Intellectual functioning in control participants was established using a short form of the Wechsler Intelligence Scales (either WPPSI-R, WISC-III-R, or WAIS-R), consisting of two Verbal (information and vocabulary) and two Performance (picture completion and block design) subtests. This particular short form loads highly on verbal comprehension and visualperceptual organization skills and is a reliable estimate of full-scale IQ scores (Sattler, 1992). Control participants were matched to clinical participants on the basis of full-scale IQ. One-way ANOVAs uncovered no significant difference in IQ between the HFA group and their matched controls nor between the AD group and their matched controls across the three experiments [Experiment 1: HFA/controls F(1, 22) 1.50, p .24; AD/controls, F(1, 18) 0.07, p .80. Experiment 2: HFA/controls F(1, 20) 3.68, p .07; AD/controls F(1, 16) 0.02, p .90. Experiment 3: HFA/controls F(1, 22) 3.31, p .08, AD/controls F(1, 22) 0.13, p .73] (see Tables 1 to 3 for participant details). Normal behavioral functioning was screened in both control groups using the Parent form of the Child Behaviour Checklist (CBC-L) (Achenbach, 1991). None of the control participants were reported to have levels of clinically significant behavioral problems.

325 the movement sequence. Each pair of buttons was separated by 30 mm. The rows themselves were 30 mm apart, and each button was 13 mm in diameter. The board was positioned across the participants midline. A pathway of illuminated lights (LEDs) was serially presented down the board, in which there were two-way choice points at each of the 10 sequential pairs of buttons. The production and sequence of these visual cues were controlled by a Toshiba (440 CDT Satellite Pro) Notebook computer. In all trials, participants began by pressing two single buttons to initiate the task. Thereafter, the computer generated a sequence of light cues in which one member of each of the 10 pairs of buttons was illuminated, one at a time. First, one cue from the first pair was immediately illuminated and participants had to press this button, as quickly as possible. Immediately thereafter one cue from the next pair was illuminated, and participants had to press that button and so forth along the entire board. Each movement sequence proceeded from one side of the board to the other, either from left to right or right to left. Thus, each movement in a sequence was directed only as far as the next pair of buttons. Trials were terminated at the final button. Eight different equidistant pathways were utilised. The numbers of linear and diagonal movements between successive button pairs, and hence the aggregate distance of each sequence, was constant across the pathways. The exact sequence of movements from button to button varied across trials so that participants were unable to predict their next movement before receiving a visual cue. Maximum duration of cue illumination was set at 1000 milliseconds. If a button was incorrectly pressed or was pressed twice, the trial was terminated and recorded as an error. Participants were counterbalanced such that half started with the rightward condition and half started with the leftward condition; an equal number of leftward and rightward trials were administered to each participant in a pseudo-random order. Each participant completed a total of 48 trials. Response time (RT), the duration between the illumination and depression of a button, was recorded by the computer. Mean RT and error data for leftward and rightward movements were compared between the HFA group and matched controls and between the ASs disorder and their matched controls. Experiment 2: A Simple Reaction Time, Posner Task For the second experiment, participants were positioned 60 cm in front of a Toshiba (440 CDT Satellite Pro) Notebook computer with their dominant hand

Apparatus and Procedure Experiment 1: A Choice Response-Time Movement Paradigm The response board used in experiment 1 consisted of a laminated wooden surface measuring 480 100 mm; 23 spring-loaded, circular buttons were set into this surface (see Mattingley, Bradshaw, & Phillips, 1992). Each button was made from highly visible white plastic and was situated within a translucent circular annulus. Red light-emitting diodes (LEDs) were embedded within the annuli and served as visual cues. Twenty of these buttons were arranged in two parallel rows of 10, with three additional buttons, two of which were always pressed at the start (S1, S2) and one at the finish (F) of

326 resting on the space bar of the computer keyboard. For each trial, two gray, rectangular boxes were presented and arranged in a horizontal array on the display. Each box spanned 1.8 cm in height and 1.4 cm in width. A symbol was located in the center of the screen; the distance between the midpoint of each lateral box and the midpoint of the was 8.5 cm. After 1500 milliseconds, one of the lateral boxes became white for 50 milliseconds before returning to gray. This illumination served as a lateral cue. A red asterisk (i.e., target) was presented 700 milliseconds after the lateral cue appeared. Participants were instructed to press the space bar as soon as they detected the red asterisk. Responses that occurred between the appearance of the lateral cue and the target were deemed to be anticipations. Each participant received 200 trials. The position of the lateral cue (left vs right) was counterbalanced. For the present purposes, the aim was to determine whether the HFA and AD groups were less likely than controls to anticipate when cues were presented on the righthand side of the computer screen. This objective was assessed by considering the mean number of anticipations in response to cues on the left and right side of the screen. Experiment 3: Gray Scales and Chimeric Faces Task Chimeric faces and gray scales tasks previously used by Mattingley et al. (1994a & 1994b) were used for the third experiment. The chimeric faces set was constructed by photographing 10 persons faces twice, once with a smiling and once with a neutral expression. Each photograph was divided along the midsagittal axis and recombined to form two different mirror-image chimeras. Each chimera was then paired with its mirror image. The vertical position of each member of a pair was counterbalanced, resulting in a matched set of four pairs of chimeric stimuli from each face, yielding a total of 40 stimulus pairs (for a more detailed description of the construction and design of the chimeric faces, see Mattingley et al., 1994b). Gray scales were produced using a computer graphics package and laser printed on sheets of white A4 paper. Each gray scale was a rectangular strip, bounded by a thin black outline, with a constant height of 20 mm and eight widths varying from 120 to 260 mm in 20-mm increments. Each gray scale consisted of a semicontinuous scale of gray shades ranging from black at one end to white at the other. The shading was achieved by adjusting the size, shape, and density of pixels within adjacent vertical bands, thereby producing a virtually continuous gradient across the width of each rectangle

Rinehart, Bradshaw, Brereton, and Tonge (see Mattingley et al., 1994b). On each trial, two gray scales of equal width were presented, one above the other; the dark side of one scale was placed on the opposite side of the dark side of the other. On half of the trials, the dark side of the top scale was on the left. There were 32 items in total. The order in which the two tasks were performed was counterbalanced. Stimuli were placed approximately 30 cm in front of participants on a flat surface. The object of the chimeric faces task was to indicate which of the two faces looked happier. In the gray scales task, participants were asked to indicate which of the two rectangles appeared darker overall. In both tasks, participants responded by either saying top or bottom or by pointing to the top or bottom stimulus. A response was defined as left-biased when the participant selected the smile left chimera, or the rectangle with the dark end on the left. The converse response was defined as right-biased. The asymmetry score was calculated as the number of rightward biases minus the number of leftward biases, divided by the total number of items. Thus, negative scores indicated a leftward bias, whereas positive scores indicated a rightward bias.

RESULTS AND DISCUSSION Experiment 1: A Choice Response-Time Movement Paradigm High-Functioning Autism Response time. A two-way ANOVA was undertaken to investigate the impact of group (HFA, controls) and direction (leftward, rightward) on RT. There was a significant main effect of direction, F(1, 22) 20.27, p .001, and group-by-direction interaction, F(1, 22) 5.29, p .03 (Fig. 1a). The HFA group were not significantly slower when direction was collapsed across group, F (1, 22) 0.60, p .45. An analysis of simple main effects revealed that rightward movements were significantly slower for the HFA group, F(1, 11) 68.70, p .001, but not the control group, F(1, 11) 1.46, p .25 (Fig. 1a). Errors. An analogous two-way ANOVA conducted with the error data showed a group-by-direction interaction, F(1, 22) 4.29, p .05, but no significant main effect of direction, F(1, 22) 1.61, p .22. A subsequent analysis of simple main effects revealed more errors were committed when moving rightward than when moving leftward for the HFA group, F(1, 11) 4.82, p .05, but not for the control group, F(1, 11) 0.38, p .55 (Fig. 2a).

Lateralization in Autism and Aspergers Disorder

327

(a)

(b)

Fig. 1. Choice reaction-time movement paradigm: Mean RT (milliseconds) for rightward and leftward movements for (a) high functioning autism (HFA) and control group and (b) Aspergers disorder (AD) and control group. SE bars shown.

Aspergers Disorder Response time. The comparison of AD with controls on RT showed no effect of group, F(1, 18) 1.25, p .28, direction, F(1, 18) 3.74, p .07, or a group-bydirection interaction, F(1, 18) 0.36, p .56 (Fig. 1b). Errors. Similarly to the RT data, analyses of the error data showed no significant main effects of: group, F(1, 18) 1.06, p .32; direction, F(1, 18) 2.64, p .12; or a group-by-direction (leftward, rightward)

interaction, F(1, 18) 0.72, p .41 (Fig. 2b). Despite these nonsignificant findings, Figure 2b shows that the AD group appears to have committed more rightward errors compared with their matched control group. It is conceivable that this apparent tendency for rightward errors may have reached significance had the sample size been very much larger, although there was not even a trend toward significance. Indeed, the failure to find a rightward deficit, or even a trend

(a)

(b)

Fig. 2. Choice reaction time movement paradigm: Mean errors for rightward and leftward movements for (a) high functioning autism (HFA) and control group and (b) Aspergers disorder (AD) and control group. SE bars shown.

328 toward such a deficit, when response time was examined may indicate that the apparent rightward deficit trend depicted in the error data (see Fig. 2b) simply reflects subject variability. Indeed, further examination of individual error data indicated that two participants with AD appeared to be contributing to most of the rightward errors. Taken together, the data demonstrate that the HFA group were slower and committed more errors when moving rightward rather than leftward. Neither their matched counterparts nor the AD group exhibited these directional effects. Experiment 2: A Simple Reaction-Time, Posner Task High-Functioning Autism Anticipation responses. A two-way ANOVA was undertaken in which cue-hemispace (right, left) was manipulated within subjects and group (HFA, controls) was manipulated between subjects. There was a significant two-way interaction of group-by-cue-hemispace, F(1, 20) 7.49, p .01. As shown in Figure 3a, the HFA group committed significantly less target anticipations in response to right cues compared with left cues, F(1, 10) 14.1, p .004. However, control participants

Rinehart, Bradshaw, Brereton, and Tonge made a similar number of anticipations in response to left and right cues, F(1, 10) 0.06, p .82. Thus, the HFA group was less likely to anticipate a target when the cue was presented on the right side of the computer screen. This pattern did not arise in control participants who committed a similar number of right and left anticipation errors. Aspergers Disorder Anticipation responses. Similar analyses of the AD data revealed no main effects of group, F(1, 16) 0.92, p .35, or cue-hemispace, F(1, 16) 0.80, p .38, nor an interaction of these variables, F(1, 16) 0.36, p .56. Figure 3b shows that both the AD and control groups committed a similar number of target anticipation errors in response to right and left cues. Therefore, unlike the HFA group, the AD group did not exhibit less anticipations to right-sided cues. Thus, the HFA, but not the AD group, exhibited a right spatial, left hemispheric deficit on this task. Although there were fewer participants in the AD group (n 9) in comparison to the HFA group (n 11), the analyses for the AD group did not nearly reach significance, and thus a failure to find laterality differences between the AD and matched controls is unlikely to be a consequence of reduced statistical power.

(a)

(b)

Fig. 3. Simple reaction-time, Posner task: Mean no. of anticipation errors for cues appearing in the right and left hemi-spaces for (a) high functioning autism (HFA) and control group and (b) Aspergers disorder (AD) and control group. SE bars shown.

Lateralization in Autism and Aspergers Disorder Experiment 3: Gray Scales and Chimeric Faces Tasks High-Functioning Autism Laterality bias scores for gray scales and chimeric faces. Overall, the HFA group generated a marginal leftward bias on the gray scales task (mean asymmetry score 0.135), whereas the matched controls exhibited a marginal rightward bias (mean asymmetry score 0.104). One-way ANOVA, however, revealed no statistical difference between the groups on the asymmetry scores, F(1, 2) 2.03, p .17. Both the HFA and control groups showed a statistically similar, slight leftward bias on the chimeric faces task (mean asymmetry scores; HFA 0.091, controls 0.091), F(1, 22) 0.01, p 1.00. Aspergers Disorder Laterality bias scores for gray scales and chimeric faces. On the gray scales task, the AD group showed a slight leftward bias, whereas the controls showed a slight rightward bias (mean asymmetry scores; AD 0.068, controls 0.09); however, no statistical difference was revealed, F(1, 22) 0.88, p .36. Both groups showed a small statistically similar leftward bias on the chimeric faces task (mean asymmetry scores; AD 0.175, controls, 0.133), F(1, 22) 0.10, p .75. Thus, unlike normal, healthy adults who typically show a fairly substantial leftward bias in these tasks (see Mattingley et al. 1994a & 1994b), the normal, healthy children and adolescents and those with autism and AD showed negligible biases. General Discussion Neuroimaging and neurobehavioral evidence supporting a left hemisphere deficit in autism has been equivocal. It was proposed that left hemisphere deficits may be specific to tasks that are sensitive to executive dysfunction. We used two such tasks. The first involved controlling movement skillfully along an unpredictable light path, and the second involved responding only to a particular stimulus. Hence, both of these tasks entailed the anticipation, planning, and suppression of potential responses and thus involved executive function (Norman & Shallice, 1980). Compared with controls, the autism group displayed deficiencies in right hemispace and thus in left hemisphere performance on both of these tasks. However, the autism group exhibited no anomalies of lateralisation on the visual-perceptual, nonexecutive function task. Taken together, these studies

329 suggest a left hemisphere executive functionspecific impairment in autism. This study compliments neuroimaging studies that implicate left hemisphere functional anomalies in autism (Chiron et al., 1995; Fernell et al., 1997; Siegel et al., 1992) and extends past neurobehavioral research by using tasks that do not merely infer hemispheric processing (see Arnold & Schwartz, 1983; Sussman & Lewandowski, 1990, for a review). The AD group performed similarly to their matched controls on all three tasks, thus showing laterality patterns typical for their age and IQ. Although executive dysfunction and frontostriatal anomalies have been implicated in both autism and AD (Gillberg, 1998; Maurer & Damasio, 1982; Nyden et al., 1999; Ozonoff & Jensen, 1999; Pennington & Ozonoff, 1996), these findings suggest that a lateralized disturbance within the frontostriatal circuitry may be specific to autism. This examination of laterality in the context of executive dysfunction may also provide further means for dissociating autism and AD from other neurodevelopmental disorders with frontostriatal disorders. Indeed, the concept of executive dysfunction has been widely used as a tool for measuring neurobehavioral differences between autism, AD, and attention deficit hyperactivity disorder. Nyden, Gillberg, Hjelmquist, and Heiman (1999) found that AD shares a similar profile of executive dysfunction as attention deficit hyperactivity disorder. Ozonoff and Jensen (1999) found that autism can be distinguished from attention deficit hyperactivity disorder on the basis of preserved performance on tasks measuring inhibition. Using a line-bisection task that is sensitive to executive dysfunction, Sheppard, Bradshaw, Mattingley, and Lee (1999) uncovered right hemisphere anomalies in attention deficit hyperactivity disorder. The converse finding of left hemisphere anomalies in autism using tasks sensitive to executive dysfunction may thus demonstrate another way in which these disorders may be distinguished from attention deficit hyperactivity disorder. It may be that the direction of anomalous lateralization (e.g., left or right hemispheric dysfunction) in frontostriatal disorders is related to the severity and pervasive nature of the neurodevelopmental condition. For example, in contrast to the right hemisphere dysfunction seen in attention deficit hyperactivity disorder, a condition that individuals often grow out of, individuals with more chronic and debilitating conditions such as schizophrenia exhibit LHD, for example, problems detecting invalidly cued targets presented in the right hemispace (Posner, Early, Reiman, Pardo, et al., 1988) and problems coordinating rightwardly directed

330 cognitive-motor responses (Williams et al., 2000). Historically, autism was described as a form of childhood psychosis, and although contemporary diagnostic criteria clearly separate autism from psychotic disorders (American Psychiatric Association, 1994), several studies have shown that a schizophrenic-like condition may be associated with some cases of autism (Sverd, Montero, & Gurevich, 1993). Thus, in addition to the LHD theory, LHD in autism would also be predicted by the clinical chronicity and pervasive nature of this disorder and, in particular, its relationship to schizophrenia. Evidence supporting LHD in autism, but not AD, may have etiological relevance and is therefore interesting to consider in the context of brain development. Chiron et al. (1995) examined the development of functional brain asymmetry in normal, healthy, children using single-photon emission computed tomography. These authors uncovered a right hemisphere dominance between the ages of 1 and 3 years, and a left dominance after 3 years of age (Chiron et al., 1995). It was suggested that the shift to left hemispheric dominance coincides with language development and that the later development of this hemisphere renders it more vulnerable to brain damage (e.g., epilepsy). Conceivably, the period where dominance shifts from the right to the left hemisphere is important in whatever process might dictate the emergence of either autism or AD. This proposal implies that right hemisphere dysfunction may be involved in both autism and AD, with additional LHD only occurring in autism, thereby delaying language development. Indeed, there is evidence to suggest that a number of right hemisphere anomalies are common to both disorders (Blackstock, 1978; Dawson, 1983; Fein, Humes, Kaplan, Lucci, & Waterhouse, 1984; Jolliffe & Baron-Cohen, 1997; Prior & Bradshaw, 1979; Tanguay, 1976). There is an apparent anomaly in our argument that right hemisphere visual-perceptual anomalies may be common to autism and AD, even though no visualperceptual/right hemisphere anomalies were observed in experiment 3. This contradiction may be reconciled by our original argument that the neurobiological dysfunction underpinning these disorders may affect higher-order, executive function processes. Lowerlevel, basic perceptual processes, such as those invoked in the gray scales and chimeric faces task, may remain relatively intact. In summary, this study uncovered neurobehavioral evidence to suggest that LHD in autism is most prominent on executive function tasks, thus implicating a spe-

Rinehart, Bradshaw, Brereton, and Tonge cific disruption of the frontostriatal circuitry. No such hemispheric deficit was uncovered for the AD group. The establishment of left hemisphere dominance may be a significant event in the differential etiology of these disorders. Finding a qualitative neuropsychological dissociation between autism and AD perhaps suggests that these disorders have differentially disrupted frontostriatal circuitry. The main limitation of this study is the possibility that the lateralization effects observed for the children with autism were task dependent. It will therefore be important for future researchers to further investigate left hemisphere deficiencies and executive dysfunction in this group using a broader range of tasks that invoke executive and, indeed, nonexecutive functions. Just as Baron-Cohen and Swettenham (1997) have made important links between cognitive deficits associated with theory-of-mind, central coherence, and executive function, the notion that executive and LHD may also be linked represents further advancement toward integrating neuropsychological findings.

ACKNOWLEDGMENTS The authors would like to thank all of the participating families, and also the children from St. Bernadettes Primary School who participated as controls. This research is supported by Cure Autism Nows Young Investigator fellowship program, with resources provided in part by the Autism Coalition for Research and Education. This research was also supported by the Australian Research Council, Soroptimists International, and The Queens Trust for Young Australians. We would like to gratefully acknowledge the research assistance of Judith Bradshaw.

REFERENCES
Achenbach, T. M. (1991). Manual for the child behavior checklist, 418 and 1991 Profile. Burlington, VT: Department of Psychiatry, University of Vermont. American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: American Psychiatric Association. Arnold, G., & Schwartz, S. (1983). Hemispheric lateralization of language in autistic and aphasic children. Journal of Autism and Developmental Disabilities, 13, 129139. Baron-Cohen, S., & Swettenham, J. (1997). Theory of mind in autism: Its relationship to executive function and central coherence. In D. J. Cohen & F. R. Volkmar (Eds.), Handbook of autism and pervasive developmental disorders, 2nd Edition (pp. 880894). New York: John Wiley & Sons Inc.

Lateralization in Autism and Aspergers Disorder

Blackstock, E. G. (1978). Cerebral asymmetry and the development of early infantile autism. Journal of Autism and Childhood Schizophrenia, 8, 339353. Bradshaw, J. L. (2001). Developmental disorders of the frontostriatal System: Neuropsychological, neuropsychiatric and evolutionary perspectives. Hove: Psychology Press/Taylor and Francis. Chiron, C., Leboyer, M., Leon, F., Jambaque, I., Nuttin, C., & Syrota, A. (1995). SPECT of the brain in childhood autism: evidence for a lack of normal hemispheric asymmetry. Developmental Medicine and Child Neurology, 37, 849860. Damasio, H., Maurer, R. G., Damasio, A. R., & Chui, H. C. (1980). Computerized tomographic scan findings in-patients with autistic behaviour. Archives of Neurology, 37, 504510. Dawson, G. (1983). Lateralized brain dysfunction in autism: evidence from the Halstead-Reitan neuropsychological battery. Journal of Autism and Developmental Disorders, 13, 269286. Ellis, H. D., Ellis, D. M., Fraser, W., & Deb, S. (1994). A preliminary study of right hemisphere cognitive deficits and impaired social judgments among young people with Asperger syndrome. European Child and Adolescent Psychiatry, 3(4), 255266. Fein, D., Humes, M., Kaplan, E., Lucci, D., & Waterhouse, L. (1984). The question of left hemisphere dysfunction in infantile autism. Psychological Bulletin, 95(2), 258281. Fein, D., Joy, S., Green, L. A., & Waterhouse, L. (1996). Autism and pervasive developmental disorders. In B. S. Fogel, R. B. Schiffer, & S. M. Rao (Eds.), Neuropsychiatry (pp. 571601). Baltimore: Williams & Wilkins. Fernell, E., Watanabe, Y., Adolfsson, L., Tani, Y., Bergstrom, M., Hartvig, P., et al. (1997). Possible effects of tetrahydro-biopterin treatment in six children with autism: clinical and positron emission tomography data: a pilot study. Developmental Medicine and Child Neurology, 39, 313318. Frith, C., & Dolan, R. (1997). The role of the prefrontal cortex in higher cognitive functions. A. C. Roberts, T. W. Robbins, & L. Weiskrantz (Eds.). The prefrontal cortex: Executive and cognitive functions. Oxford: Oxford University Press. Gillberg, C. (1998). Asperger syndrome and high-functioning autism. British Journal of Psychiatry, 172, 200209. Happ, F., Ehlers, S., Fletcher, P., Frith, U., Johansson, M., & Billberg, C. (1996). Theory of mind in the brain: evidence from a PET scan study of Asperger syndrome. NeuroReport, 8, 197201. Hauser, S. L., DeLong, G. R., & Rosman, N. P. (1975). Pneumographic studies in the infantile autism syndrome. Brain, 98, 667 688. Hier, D. B., LeMay, M., & Rosenberger, P. B. (1979). Autism and unfavourable left-right asymmetries of the brain. Journal of Autism and Developmental Disorders, 9, 153159. Jolliffe, T., & Baron-Cohen, S. (1997). Are people with autism and Asperger syndrome faster than normals on the Embedded Figures Test. Journal of Child Psychology & Psychiatry & Allied Disciplines, 38(5), 527534. Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism & Developmental Disorders, 24(5), 659685. Mattingley, J. B., Bradshaw, J. L., Bradshaw, J. A., & Nettleton, N. C. (1994a). Residual rightward attentional bias after apparent recovery from right hemisphere damage: implications for a multicomponent model of neglect. Journal of Neurology, Neurosurgery, and Psychiatry, 57, 597604. Mattingley, J. B., Bradshaw, J. L., Nettleton, N. C., & Bradshaw, J. A. (1994b). Can task specific perceptual bias be distinguished from unilateral neglect? Neuropsychologia, 32(7), 805817. Mattingley, J. B., Bradshaw, J. L., & Phillips, J. G. (1992). Impairments of movement initiation and execution in unilateral neglect. Brain, 115, 18491874.

331
Maurer, R. G., & Damasio, A. G. (1982). Childhood autism from the point of view of behavioral neurology. Journal of Autism and Developmental Disorders, 12(2), 195205. McKelvey, J. R., Lambert, R., Mottron, L., & Shevell, M. I. (1995). Right-hemisphere dysfunction in Aspergers syndrome. Journal of Child Neurology, 10(4), 310314. Minshew, N. J., Sweeney, J. A., & Bauman, M. L. (1997). Neurological aspects of autism. In D. J. Cohen & F. R. Volkmar (Eds.), Handbook of autism and pervasive developmental disorders (2nd ed., pp. 344370). New York: John Wiley & Sons. Miyake, A., Friedman, N. P., Emerson, M. J., Witzki, A. H., & Howerter, A. (2000). The unity and diversity of executive functions and their contributions to complex frontal lobe tasks: a latent variable analysis. Cognitive Psychology, 41, 49100. Muller, R. A., Behen, M., Rothermel, R., Chugani, D., Muzik, O., Mangner, T., & Chugani, H. (1999). Brain mapping of language and auditory perception in high-functioning autistic adults: a PET study. Journal of Autism and Developmental Disorders, 29(1), 1931. Nicholls, M. E. R., Bradshaw, J. L., & Mattingley, J. B. (2001). Unilateral hemispheric activation does not affect free-viewing perceptual asymmetries. Brain & Cognition, 46(1), 219223. Norman, D. A., & Shallice, T. (1980). Attention to action: Willed and automatic control of behaviour. Center for Human Information Processing Technical Report, 99. Nyden, A., Gillberg, C., Hjelmquist, E., & Heiman, M. (1999). Executive function/attention deficits in boys with Asperger syndrome, attention disorder and reading/writing disorder. Autism, (3), 213228. Ozonoff, S., & Jensen, J. (1999). Brief report: Specific executive function profiles in three neurodevelopmental disorders. Journal of Autism and Developmental Disorders, 29(2), 171177. Ozonoff, S., & Miller, J. N. (1996). An exploration of right-hemisphere contributions to the pragmatic impairments of autism. Brain & Language, 52(3), 411434. Pennington, B. F., & Ozonoff, S. (1996). Executive functions and developmental psychopathology. Journal of Child Psychology and Psychiatry, 37(1), 5187. Posner, M., I, Early, T. S., Reiman, E., Pardo, P. J., et al. (1988). Asymmetries in hemispheric control of attention in schizophrenia. Archives of General Psychiatry, 45(9), 814821. Prior, M. R., & Bradshaw, J. L. (1979). Hemisphere functioning in autistic children. Cortex, 15, 7381. Rinehart, N. J., Bradshaw, J. L., Moss, S. A., Brereton, A. V., & Tonge, B. J. (2000). Atypical interference of local detail on global processing in high functioning autism and Aspergers disorder. Journal of Child Psychiatry and Psychology, 41(6), 796778. Rumsey, J. M., & Hamburger, S. D. (1988). Neuropsychological findings in high-functioning men with infantile autism, residual state. Journal of Clinical and Experimental Neuropsycholgy, 10, 201221. Rutter, M., & Bailey, A. (1993). Thinking and relationships: Mind and brain -some reflections on theory of mind and autism. In S. Baron-Cohen, H. Tager-Flusberg, & D. Cohen (Eds.), Understanding other minds: perspectives from autism (pp. 481 504). Oxford: Oxford University Press. Sabbagh, M. A. (1999). Communicative intentions and language: evidence from right hemisphere damage and autism. Brain and Language, 70, 2969. Sattler, J. M. (1992). Assessment of children: Revised and updated third edition. (3rd ed.). San Diego: Jerome M. Sattler, Publisher, Inc. Sheppard, D. M., Bradshaw, J. L., Mattingley, J. B., & Lee, P. (1999). Effects of stimulant medication on the lateralisation of line bisection judgements of ADHD children. Journal of Neurology, Neurosurgery & Psychiatry, 66(1), 5763. Siegel, B. V., Asarnow, R., Tanguay, P., Call, J. D., Abel, L., Ho, A., Lott, I., & Buchsbaum, M. S. (1992). Regional cerebral

332
glucose metabolism and attention in adults with a history of childhood autism. The Journal of Neuropsychiatry and Clinical Neurosciences, 4(4), 406414. Stuss, D. T., & Alexander, M. P. (2000). Executive functions and the frontal lobes: a conceptual view. Psychological Research, 63, 289298. Sussman, K., & Lewandowski, L. (1990). Left-hemisphere dysfunction in autism: What are we measuring? Archives of Clinical Neuropsychology, 5, 137146. Sverd, J., Montero, G., & Gurevich, N. (1993). Brief report: Cases for an association between Tourette syndrome, autistic disorder, and schizophrenia-like disorder. Journal of Autism and Pervasive Developmental disorders, 23(2), 407413.

Rinehart, Bradshaw, Brereton, and Tonge

Tanguay, P. E. (1976). Clinical and electrophysiological research. New York: Spectrum. Wainwright, J. A., & Bryson, S. E. (1996). Visual-spatial orienting in autism. Journal of Autism and Developmental Disorders, 26(4), 423 438. Williams, S. B. K., Phillips, J. G., Bellgrove, M. A., Bradshaw, J. L., Bradshaw, J. A., & Pantelis, C. (2000). Use of advanced information in patients with schizophrenia. Journal of Clinical and Experimental Neuropsychology, 22(4), 427482. Zilbovicius, M., et al (2000). Temporal lobe dysfunction in childhood autism: a PET study. The American Journal of Psychiatry, 157(12), 19881993.

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