We found significant differences in brain activity in children and adolescents with ASD compared with TD controls during the interpretation of a speaker’s communicative intent. First, as compared with TD children, children with ASD exhibited a less selective response to potentially ironic scenarios relative to unambiguous scenarios as indicated by reduced activity in the MPFC and right STG. Second, a significant group × condition interaction in the MPFC showed that regional activity was modulated by explicit instructions to attend to facial expression and tone of voice only in children with ASD. However, regardless of instructions, less activity was observed in the STG bilaterally in children with ASD relative to TD children during the irony conditions compared with rest. Finally, MPFC activity was inversely related to symptom severity in the ASD group such that greater social competence was associated with greater activity in the MPFC across all irony conditions. Importantly, these differences were significant after controlling for VIQ.
A less selective neural response to ironic scenarios relative to straightforward scenarios in children with ASD coheres with behavioral evidence that these individuals often mistakenly attribute a literal meaning to ironic utterances.37,49
Previous research suggests that the MPFC is important for understanding others’ mental states50
and that right-hemisphere temporal regions are engaged when coherence seeking is required.51–54
Selective activity in these regions in TD children for ironic scenarios likely reflects a greater need to integrate facial, prosodic, and contextual cues to infer the speaker’s intent when the literal meaning of a remark conflicts with other available information. Reduced differential activity in this network in children with ASD may indicate less integrative reasoning about intent. Several other studies have also observed abnormalities in MPFC activity in individuals with ASD using a variety of tasks, including theory of mind5,27–29
and semantic processing.25
The one region where the ASD group showed greater selective activity than the TD group for ironic vs control scenarios was the angular gyrus, known to play an important role in semantic processing. Greater activity in the right angular gyrus in children with ASD than in controls could reflect more reliance on semantic processing at the word or sentence level, perhaps at the expense of integrative processing. However, once VIQ was taken into account, between-group differences in this region were no longer significant. This suggests that increased activity in the ASD group may reflect impaired verbal abilities rather than a true difference in semantic representation.
Perhaps most interesting is the finding that for children with ASD, explicit instructions to attend to facial expression or tone of voice elicited significantly greater activity in the MPFC than neutral instructions simply to pay attention. In contrast, TD children showed significant MPFC activity irrespective of instructions, consistent with evidence that this region is normally recruited automatically when processing communicative intentions.55
Our findings extend previous work suggesting that attention to crucial aspects of social stimuli can yield increased activity in regions that typically respond preferentially to such stimuli. Hadjikhani et al56
observed comparable levels of FG activity in individuals with ASD and controls when faces were presented with a red fixation cross at approximately eye level. Similarly, Dalton et al18
found that in individuals with ASD, FG activity increased with time spent looking at the eyes. With respect to understanding others’ intentions, we recently found that children with ASD engaged neurocircuitry similar to that of TD controls when task demands implicitly required attention to prosodic or contextual cues to detect ironic intent.5
However, in a natural communicative setting, relevant cues are not experimentally highlighted. Interpreting irony correctly is likely to involve selectively attending to crucial cues (eg, facial expression and tone of voice) in a dynamic environment and integrating this information to reason about mental states.57
Here, increased MPFC activity in the ASD group following explicit instructions to attend to facial expression and tone of voice may reflect more reasoning about a speaker’s communicative intent afforded by increased attention to these important cues. The significant association between MPFC activity during irony conditions and social competence in the ASD group suggests that recruitment of this region when inferring communicative intent is indicative of greater success in real-world social situations.
Regardless of task instructions, reduced activity was observed in the STG bilaterally in the ASD group relative to controls. Previous research has demonstrated that the superior temporal sulcus or STG plays a role in polymodal sensory integration and shows a greater response to congruent audiovisual stimuli than to either auditory or visual stimuli alone.58–60
Reduced STG activity during irony conditions in children with ASD could reflect difficulty detecting the correspondence between facial expression and tone of voice. This notion is consistent with behavioral studies suggesting that children with autism are impaired in matching facial and vocal affect.61,62
To our knowledge, this study is the first to demonstrate that explicit instructions to attend to important social stimuli can elicit greater activity in the MPFC, a region normally recruited automatically while attempting to infer the communicative intent of another person. Along with other work,16–19,56
our results suggest that previous reports of hypoactivation in regions supporting the processing of socially relevant information may result from a primary impairment in social interest rather than a fundamental deficit in neural functioning. A lack of attention to faces, voices, and other social stimuli may impair the development of expertise in perceiving and using social cues as well as the automatic engagement of relevant neural circuitry.63,64
The finding that specific instructions to attend to important social cues resulted in a normalization of MPFC activity in children and adolescents with ASD suggests a strategy for intervention. Adolphs et al65
recently showed that explicitly instructing a patient with bilateral amygdala damage to look at the eyes enabled normal recognition of fearful expressions. Similarly, our findings suggest that instructing individuals with ASD to attend to faces and voices may facilitate the extraction of information necessary for interpreting others’ communicative intentions. An approach that combines instruction to use top-down cognitive strategies with perceptual training and reinforcement to facilitate bottom-up attentional processes could capitalize on cognitive strengths while addressing weaknesses in automatic mechanisms. Attentional training in different contexts should result in greater recruitment of the MPFC, perhaps enabling more efficient integration of socially relevant cues. In turn, this may lead to greater success in understanding others’ intentions in everyday interactions. Attention to faces and voices may then become more rewarding and more automatic for individuals with ASD, ultimately leading to higher levels of social responsiveness.
This study has some limitations. First, instructions to attend to the face and voice did not result in enhanced behavioral performance in the ASD group. This is likely due to the simplicity of the scenarios, which had a visual depiction of the event outcome. Performance was excellent even when no attentional guidance was provided. Although prompting the ASD group to attend to facial and prosodic cues may lead to the recruitment of more normative neurocircuitry, behaviorally, more time and practice may be needed before a performance benefit is derived. Compensatory mechanisms developed over time by individuals with ASD are likely to be effective for simple scenarios similar to those used here but are unlikely to be adequate for inferring intent in more dynamic social situations. A second limitation is that the TD and ASD groups differed significantly in VIQ. This leaves open the possibility that our results could be influenced by differences in verbal abilities because task performance increased significantly with VIQ in both groups. However, across all irony conditions, neither VIQ nor accuracy was significantly related to activity in the MPFC, the main site of differences, in either group. A third limitation concerns the possible comorbidity of ASD and ADHD. Although we excluded individuals with a concurrent ADHD diagnosis, some participants were receiving medication, including stimulants. Given that excluding individuals receiving medication did not significantly alter the results and that impairment in theory of mind has not been associated with ADHD,66,67
we feel it is unlikely that comorbid ADHD significantly impacted our findings. A fourth limitation is that the length of the scenarios in our activation paradigm precluded the use of an event-related design, which would have allowed us to tease apart the neural response to ironic vs sincere scenarios. This compromise was made in the framework of examining the neural processes involved in interpreting communicative intent as a whole rather than assuming that inferring irony and inferring sincerity are independent functional processes.68
Finally, the age of our participants varied considerably. Although chronological age was not significantly associated with activity in regions where between-group differences were observed, future research should explore developmental changes in the neural networks supporting the interpretation of communicative intent in ASD.