Consistent with prior behavioral studies of the inversion effect in ASD, our typically developing children showed a larger performance decrement for inverted compared with upright faces than did the children with autism. This replicates prior findings in the literature showing a reduced or absent inversion effect in ASD while confirming a significant inversion effect in typically developing children. However, this effect was due not to superior performance in ASD for inverted faces, but rather to relatively impaired performance on upright faces. It is important to note that the performance results are based on reaction time, not accuracy data, as the latter showed strong ceiling effects in this task. FMRI results showed that group differences were found in the frontal cortex for both upright and inverted tasks. Moreover, we did not detect differences between ASD and TD children in the fusiform gyrus region for either condition. Rather, the significant differences in brain activity between groups were found in inferior and middle frontal brain regions as well as in the amygdala. These data suggest that key differences in face processing in children with autism are due to differences in brain regions involving fronto-limbic systems. Our data are inconsistent with the notion that the inversion effect can be explained by altered activity in the FFA, because FFA activity was the same between ASD and TD groups. Instead, the brain areas that differentiated ASD from TD children during both of the face processing tasks were found primarily in several brain regions typically associated with the so-called “social brain: (Hadjikhani et al., 2007
; Frith, 2007
). In frontal cortex, activation was extensive for typically developing children and was more active than in ASD children for all conditions. The most unique areas of activation differences were found in the left hemisphere, in the dorsal portion of the inferior frontal gyrus. Aside from its role on language, this region has been reported in studies of “mirror neuron” activity in normal adults (Iacoboni, 2005
), and is less active during imitation and observation of faces in children with autism compared to TD children (Dapretto et al., 2006
). The “mirror neuron” areas, including frontal and limbic brain regions, play a specific role in processing meaningful, goal directed behaviors that are observed in others by effectively mirroring those behaviors internally, and appear to be related to social cognition (Iacoboni & Dapretto, 2006
). Hadjikhani et al. (2007)
also found reduced activity in the IFG during face processing in autism though in the right hemisphere, while Dapretto et al. (2006)
found bilateral reductions in this region among ASD children. Structural abnormalities of the IFG have also been reported in autism (Hadjikhani et al., 2006
). Together these data suggest that IFG dysfunction is a consistent finding in autism spectrum disorders.
Another region associated with the “social brain” network is the amygdala. While prior studies have noted amygdala differences between ASD and TD children when observing faces bearing emotional expressions (e.g., Pelphrey et al., 2007
; Piggot et al., 2004
; Wang et al., 2004
), the stimuli used in the present study were of neutral expression suggesting that face stimuli may automatically invoke neural activity in this region among TD children. The IFG is thought to project to the amygdala via
the insula in a pathway that may add an emotional valence to processing the intentions of others (Carr et al., 2003
; Dapretto et al., 2006
). Abnormal fronto-limbic development in children with autism may contribute to their deficits in social cognition.
While the interpretation of the inversion effect in autism remains controversial, one argument is that ASD children do not visually process faces as unique entities, instead perceiving them similarly to other objects (Hobson et al., 1988
), and thus are less hampered by inversion. Alternatively, ASD children may typically engage more in component rather than configural processing, a strategy that could be applied across stimulus types but may be better suited for inverted faces (Ashwin et al., 2006
). The hypothesis that the fusiform face area typically processes information configurally has been challenged in recent fMRI studies. Yovel and Kanwisher (2004)
argued that in normal adults, face processing takes place uniquely in the FFA regardless of whether subjects apply a configural or parts-based task, and regardless of whether the faces are upright or inverted (Yovel & Kanwisher, 2005
), though activation was somewhat greater for upright faces. Other studies have found no difference between upright and inverted faces in the FFA (Aguirre et al., 1999
; Haxby et al., 1999
). Prior studies have shown mixed results on whether ASD children show abnormal responses in the FFA. While many earlier studies found reduced FFA activity in ASD (Pierce et al., 2001
; Schultz et al., 2000
) others, particularly those in which the faces were familiar to the subjects (Pierce et al., 2004
) or when the tasks required subjects to maintain fixation on the faces showed no FFA differences (Pelphrey et al., 2005
; Piggot et al., 2004
; Wang et al., 2004
). In the present study, the task demands to match the faces in the inverted condition required subjects to remain focused on the face stimuli; avoiding the face would be expected to impair performance significantly. Although ASD subjects performed slightly worse than control subjects for upright faces, their overall accuracy of 93% indicates they performed the task well and thus must have processed the faces. Therefore, we cannot easily attribute the differential behavioral inversion effect to differences in visual aspects of face processing in the present study.
We found greater activation in all regions of interest for the inverted task. This finding may relate to the increased difficulty of the inverted task generally. Prior studies of task difficulty show increases in fMRI activation, more specifically in frontal cortex and sensory processing regions, as task demands increase (e.g., Burggren et al., 2002
; Kroger et al., 2002
). However, post hoc
analyses correlating task performance with fMRI responses found no evidence that performance differences between subjects could account for the selective group differences in PFC activation in our study.
Of interest, one brain area in which ASD subjects showed increased activity compared with controls was the precuneus. Prior imaging studies of ASD using a range of paradigms have also implicated this region (Wang et al., 2004
), which is thought to be a primary part of the “resting” brain network (Raichle et al., 2001
). The significance of this network is not well understood; it appears to be consistently reduced in activity when subjects engage in any kind of effortful task, and increases during rest (Raichle et al., 2001
; Raichle & Snyder, 2007
). Increased activation in this region could reflect a failure of children with autism to move away from a resting or internally directed state. Further studies focusing on this region, including resting-state studies, may help to elucidate the role of this region in autism.
There are several limitations of this study. A ubiquitous potential confound in face processing studies is that ASD subjects may tend to avert their gaze or spend less time looking at the face stimuli (Klin et al., 2002
); this may result in decrease activity in the face area (Dalton et al., 2005
). While we were unable to record eye movements in the scanner, the nature of the task we used demanded prolonged exposure and/or attention to the faces; thus, the tendency for ASD subjects to avoid looking at the faces would be lessened, as they could not achieve adequate performance if they averted their gaze. If they had averted gaze, we would expect less activation in the face areas, whereas we found equivalent activation magnitudes in this region.
Another potential limitation is the number of subjects; while 12 subjects per group is considered sufficient for standard comparisons, the heterogeneity of autism makes it possible that we failed to observe subgroups with unique patterns of responses. One study found different inversion effects for those with more general face processing deficits but typical effects for those without severe face processing problems (Teunisse & de Gelder, 2003
). It is possible that a heterogenous sample may mask deficits in visual information processing seen in some studies of autism.
Finally, a strong ceiling effect in accuracy for the TD group precluded our performing analysis on accuracy data. The majority of face inversion studies use accuracy rather than reaction time to determine inversion effects (e.g., Freire et al., 2000
; Yin, 1969
). However, similar inversion effects for reaction time and accuracy have been reported in prosopagnosic patients (Farah et al., 1995b
) as well as in children with autism (Ashwin et al., 2006
), suggesting that the results from RT and accuracy measures may be comparable.
In summary, our study corroborates prior research showing a reduced inversion effect during face processing in autism; however, our data suggest this is due to impaired face processing generally, not enhanced inverted face processing as has been suggested previously. Neuroanatomically, we find no evidence that activation differences in the fusiform gyrus underlie this effect. Rather, our findings suggest that face processing differences that underlie the differential inversion effect in autism spectrum disorders are primarily represented in frontal cortex and in the amygdala, and thus appear to reflect differences in processing the meaning and significance of faces. This study adds to a growing body of evidence from structural (Hadjikhani et al., 2006
) and functional (e.g., Dapretto et al., 2006
; Hadjikhani et al., 2007
) imaging implicating top-down mechanisms for abnormal face processing in autism.