Atypical neural networks for social orienting in autism spectrum disorders

Abstract

Autism spectrum disorders (ASD) are characterized by significant social impairments, including deficits in orienting attention following social cues. Behavioral studies investigating social orienting in ASD, however, have yielded mixed results, as the use of naturalistic paradigms typically reveals clear deficits whereas computerized laboratory experiments often report normative behavior. The present study is the first to examine the neural mechanisms underlying social orienting in ASD in order to provide new insight into the social attention impairments that characterize this disorder. Using fMRI, we examined the neural correlates of social orienting in children and adolescents with ASD and in a matched sample of typically developing (TD) controls while they performed a spatial cueing paradigm with social (eye gaze) and nonsocial (arrow) cues. Cues were either directional (indicating left or right) or neutral (indicating no direction), and directional cues were uninformative of the upcoming target location in order to engage automatic processes by minimizing expectations. Behavioral results demonstrated intact orienting effects for social and nonsocial cues, with no differences between groups. The imaging results, however, revealed clear group differences in brain activity. When attention was directed by social cues compared to nonsocial cues, the TD group showed increased activity in frontoparietal attention networks, visual processing regions, and the striatum, whereas the ASD group only showed increased activity in the superior parietal lobule. Significant group × cue type interactions confirmed greater responsivity in task-relevant networks for social cues than nonsocial cues in TD as compared to ASD, despite similar behavioral performance. These results indicate that, in the autistic brain, social cues are not assigned the same privileged status as they are in the typically developing brain. These findings provide the first empirical evidence that the neural circuitry involved in social orienting is disrupted in ASD and highlight that normative behavioral performance in a laboratory setting may reflect compensatory mechanisms rather than intact social attention.

Introduction

Autism spectrum disorders (ASD) are characterized by profound deficits in social communication and interaction. One of the most notable aspects of these social impairments is reduced orienting in response to social cues (e.g., eye gaze, pointing gestures). Converging behavioral and neural evidence shows that this deficit is not simply the result of impaired sensory processing of social stimuli, but rather a more specific impairment in social attention. For example, neuroimaging studies have demonstrated decreased activity in brain regions involved in processing faces, emotions, and voices in ASD (Critchley et al., 2000, Dalton et al., 2005, Gervais et al., 2004). Yet, when ASD individuals are cued to attend to the social stimuli, activity in these regions normalizes (Hadjikhani et al., 2004, Wang et al., 2004, Wang et al., 2007). Pelphrey et al. (2005) also found that individuals with ASD showed normal activation of the superior temporal sulcus (STS) when viewing gaze shifts. However, STS activity varied depending on the intentions conveyed by the gaze shift in control participants, while no such difference was found in the ASD group. Thus, impaired orienting in response to social cues (social orienting) in ASD likely results from impaired attentional responses to social stimuli.

Naturalistic studies investigating social orienting provide compelling behavioral evidence for impaired utilization of social cues among children with ASD. For example, these children fail to orient their attention toward social stimuli significantly more than typically developing (TD) children and those with Down syndrome (Dawson et al., 1998). Moreover, ASD children fail to shift their attention toward novel objects selectively when these objects are cued socially by a head turn and gaze shift (Leekam et al., 2000). Consistent with these findings, retrospective studies examining the home movies of infants prior to ASD diagnosis have shown that those infants who will later be diagnosed with ASD displayed less social orienting behavior, including reduced orienting to faces and following pointing gestures (Osterling and Dawson, 1994, Osterling et al., 2002, Werner et al., 2000). Thus, both orienting toward a social stimulus and orienting toward an object that is cued by a social stimulus are clearly impaired in children with ASD in naturalistic situations.

Surprisingly, computerized laboratory experiments do not show similar deficits. Social orienting can be tested in the laboratory using a variant of Posner's spatial cueing paradigm (1980) in which a social spatial cue (e.g., eyes gazing to the side) precedes a target stimulus. Even when the direction of the cue (gaze) is not predictive of the location of the upcoming target, adults and children show faster responses to targets occurring in the cued location than in an uncued location (Driver et al., 1999, Friesen and Kingstone, 1998, Ristic et al., 2002). This facilitation effect is thought to reflect an automatic shift in attention toward the cued location (Friesen et al., 2005, Langton et al., 2000). Most gaze cueing studies in ASD adults and children report intact facilitation effects and no differences in those effects between ASD and TD controls using dynamic gaze cues (Chawarska et al., 2003, Swettenham et al., 2003), static gaze cues (Kylliainen and Hietanen, 2004, Vlamings et al., 2005), and even counterpredictive gaze cues (Senju et al., 2004). To our knowledge, only two studies using a computerized gaze cueing paradigm found impaired social orienting in ASD (Goldberg et al., 2008, Ristic et al., 2005). Thus, most of the evidence suggests that both children and adults with ASD automatically orient toward the location indicated by gaze cues presented on a computer screen.

It should be noted, however, that some differences have been observed between ASD and TD performance despite intact facilitation effects. For example, one study found that TD adults responded more slowly for social cues than for nonsocial cues, whereas ASD adults showed no difference (Vlamings et al., 2005), and another showed that TD children were slower in social cueing tasks than ASD children (Chawarska et al., 2003). Others found that TD children responded at similar speeds to social and nonsocial cues, while ASD children were faster for social cues (Senju et al., 2004). Further, using counterpredictive cues, Senju et al. demonstrated that gaze cues were more effective than arrow cues in automatically orienting attention in TD children, with no such difference in ASD children. Still, the failure to find differences in the facilitation effect of social cues is perplexing, especially in light of the clear impairments reported in naturalistic paradigms.

Considering the underlying neural mechanisms involved in social orienting may help reconcile these discrepant findings. Neuroimaging studies investigating gaze perception have found that the superior temporal sulcus (STS) plays a prominent role in processing gaze (Hoffman and Haxby, 2000, Hooker et al., 2003). In addition, when Hoffman and Haxby (2000) compared neural activity for viewing averted gaze to that for viewing directed gaze (toward the participant), they also found stronger activity in the intraparietal sulcus (IPs), a region of the posterior parietal cortex (PPC) that is part of a frontoparietal network consistently implicated in attentional orienting (Corbetta and Shulman, 2002, Mesulam, 1981). Heightened STS and PPC activity has also been found among adults and children when viewing gaze shifts (Mosconi et al., 2005, Pelphrey et al., 2003). Moreover, neurotypical adults displayed differential activation in the STS and PPC when comparing gaze shifts that met versus those that violated expectations (Pelphrey et al., 2003), whereas ASD adults did not (Pelphrey et al., 2005). Thus, activity in the STS and PPC has already provided some clues as to how individuals with ASD process social stimuli.

Only a handful of neuroimaging studies have investigated social orienting using a spatial cueing paradigm among neurotypical adults. While a few of these studies reported overlapping activation for social and nonsocial cues in frontoparietal regions (Greene et al., 2009, Sato et al., 2009, Tipper et al., 2008), most of these studies found differential activation during social cueing compared to nonsocial cueing, including heightened activity in the extrastriate cortex (Engell et al., 2010, Greene et al., 2009, Hietanen et al., 2006, Tipper et al., 2008), the inferior frontal gyrus (Engell et al., 2010), the medial frontal cortex (Tipper et al., 2008), and the STS (Kingstone et al., 2004), as well as reduced activity in frontoparietal regions (Hietanen et al., 2006). Thus, the typical adult brain treats social and nonsocial cues somewhat differently.

Understanding how the ASD brain processes social compared to nonsocial cues should help explain the discrepant behavioral results found in naturalistic and experimental studies. One possibility is that individuals with ASD process gaze cues as nonsocial cues, using nonsocial mechanisms that rely on lower-level directional properties of eye gaze rather than on its social significance for orienting attention (Nation and Penny, 2008). Thus, orienting behavior in simple laboratory experiments may appear intact even though there are differences in the brain that account for the impairments seen in real life situations. Thus, the goal of the present study was to use fMRI in order to reveal differences in processing even when they are not apparent in behavior. Children and adolescents with and without ASD underwent fMRI while they performed a spatial cueing task that included social (eye gaze) and nonsocial (arrow) cues. We predicted that the ASD and TD groups would show no differences at the behavioral level but would show variation in brain activity, reflecting underlying group differences in the processing of social cues. Specifically, if individuals with ASD treat social cues as nonsocial, we would expect them to display fewer differences in brain activity between the cue types than the TD group.